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Wu R, Guo J, Liu Y, Huang S, Wu P, Liu W. Angiogenesis promotion of the transplantation of human amniotic mesenchymal stem cells via the Ang-1/Tie-2 signaling pathways in Alzheimer's disease model. J Alzheimers Dis 2025:13872877251338687. [PMID: 40326004 DOI: 10.1177/13872877251338687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
BackgroundAlzheimer's disease (AD) is a progressive degenerative disease of the central nervous system, leading to cognitive decline, mental symptoms, and behavioral disorders. The comorbidity of cerebrovascular disease in AD patients will accelerate the development of cognitive impairment and dementia. Since the dysfunction of the cerebral vasculature is closely related to neuropathology in AD patients, the protection of cerebral microvascular function and the improvement of cerebral microcirculation may bring a potential path for AD treatment. Human amniotic mesenchymal cells (hAMSCs) as a more advantageous cellular therapy for AD are proven to improve AD model mice's learning and memory abilities significantly, but fewer studies on angiogenesis and blood-brain barrier recovery have been found.ObjectiveThe study aimed to analyze the changes in angiogenesis-related factors of hAMSCs transplantation in the AD model and explore the underlying molecular mechanism.MethodshAMSCs were injected into APP/PS1 and wild type (WT) mice via tail vein, and the hAMSCs distribution in the cerebral tissue and angiogenesis in the hippocampal tissues were observed.ResultshAMSCs were found in the cortex and hippocampal areas of APP/PS1 and WT mice. hAMSCs transplantation significantly increased CD31 and Tie-2 expression in AD mice compared with the control group.ConclusionsThe study indicates that hAMSCs can cross the blood-brain barrier and enter the cerebral tissue of the mouse, transplantation of hAMSCs may promote angiogenesis in the AD model. The Ang-1/Tie-2 signaling pathway may be a therapeutically attractive target for the hAMSCs treatment of AD.
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Affiliation(s)
- Rui Wu
- Department of Brain Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shaanxi Province, China
| | - Jing Guo
- Department of Brain Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shaanxi Province, China
| | - Yang Liu
- Department of Brain Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shaanxi Province, China
| | - Sirou Huang
- The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shanxi Province, China
| | - Pingping Wu
- The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shanxi Province, China
| | - Weiping Liu
- Department of Brain Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, Shaanxi Province, China
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Jiang RS, Lee CW, Lin YH, Wang JJ, Liao JB, Peng KT, Chiang YC, Chi PL. Differential efficacy of olfactory neurospheres from deviated nasal septum and chronic rhinosinusitis patients in regenerating olfactory epithelium. Stem Cell Res Ther 2025; 16:166. [PMID: 40188125 PMCID: PMC11972463 DOI: 10.1186/s13287-025-04270-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 03/11/2025] [Indexed: 04/07/2025] Open
Abstract
BACKGROUND Olfactory epithelial stem cells hold significant potential for treating olfactory dysfunction by facilitating tissue maintenance and repair. Understanding the inherent qualities of these stem cells is crucial for optimizing their therapeutic efficacy. METHODS Olfactory epithelial samples were collected from patients with deviated nasal septum (DNS) and chronic rhinosinusitis (CRS). These were cultured to form olfactory neurospheres (ONS), which were then analyzed for neural stem cell markers, neurotrophic factor production, and their ability to differentiate into olfactory sensory neurons (OSNs). The regenerative efficacy of these ONS was tested in a methimazole-induced hyposmic mouse model, with the effects on cellular senescence, apoptosis, and proliferation in the olfactory epithelium assessed. RESULTS Both DNS- and CRS-derived ONS exhibited neural stem cell characteristics. DNS-ONS displayed superior self-renewal capacity and higher neurotrophic factor production compared to CRS-ONS, which showed impaired OSN maturation and lower neurotrophic factor levels. In vivo, DNS-ONS were more effective in restoring olfaction, as evidenced by reduced cellular senescence, decreased apoptosis, and increased cell proliferation in the OE of methimazole-induced hyposmic mice. CONCLUSIONS These findings highlight the importance of selecting the appropriate ONS source for therapeutic applications, with DNS-ONS showing greater promise for olfactory epithelium repair and olfactory function restoration.
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Affiliation(s)
- Rong-San Jiang
- Department of Otolaryngology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan
- Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chiang-Wen Lee
- Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Safety Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City, Taiwan
| | - Yu-Hsuan Lin
- Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jing-Jie Wang
- Department of Otolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jia-Bin Liao
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Kuo-Ti Peng
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yao-Chang Chiang
- Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Pei-Ling Chi
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 81362, Taiwan.
- Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
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Guan A, Alibrandi L, Verma E, Sareen N, Guan Q, Lionetti V, Dhingra S. Clinical translation of mesenchymal stem cells in ischemic heart failure: Challenges and future perspectives. Vascul Pharmacol 2025; 159:107491. [PMID: 40112941 DOI: 10.1016/j.vph.2025.107491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 03/12/2025] [Accepted: 03/17/2025] [Indexed: 03/22/2025]
Abstract
Myocardial infarction (MI) with resulting congestive heart failure is one of the leading causes of death worldwide. Current therapies for treating MI, such as devices, traditional medicine, and surgeries, come with many limitations as patients in their final stages of heart failure have little chances of experiencing any reversible changes. In recent decades, Mesenchymal stem cell (MSC) based therapy has become one of the most popular and rapidly developing fields in treating MI. Their supremacy for clinical applications is partially due to their unique properties and encouraging pre-clinical outcomes in various animal disease models. However, the majority of clinical trials registered for MSC therapy for diverse human diseases, including MI, have fallen short of expectations. This review intends to discuss the recent advances in the clinical application of using MSCs for cardiac repair and discuss challenges facing the clinical translation of MSCs for cardiac regeneration such as restoration of endothelial-cardiomyocyte crosstalk, immunomodulation and immune rejection, poor homing and migration, as well as low retention and survival. Furthermore, we will discuss recent strategies being investigated to help overcome some of these challenges.
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Affiliation(s)
- Anqi Guan
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, Biomedical Engineering Program, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada
| | - Lisa Alibrandi
- TrancriLab, Laboratory of Basic and Applied Medical Sciences, Interdisciplinary Research Center "Health Science", Scuola Superiore Sant'Anna, Pisa, Italy
| | - Elika Verma
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, Biomedical Engineering Program, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada
| | - Niketa Sareen
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, Biomedical Engineering Program, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada
| | - Qingdong Guan
- Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba; Department of Immunology and Internal Medicina, University of Manitoba, Winnipeg, Canada
| | - Vincenzo Lionetti
- TrancriLab, Laboratory of Basic and Applied Medical Sciences, Interdisciplinary Research Center "Health Science", Scuola Superiore Sant'Anna, Pisa, Italy.; UOSVD Anesthesiology and Intensive Care, Fondazione Toscana G. Monasterio, Pisa, Italy
| | - Sanjiv Dhingra
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, Biomedical Engineering Program, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada.
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Zhang L, Yu Z, Liu S, Liu F, Zhou S, Zhang Y, Tian Y. Advanced progress of adipose-derived stem cells-related biomaterials in maxillofacial regeneration. Stem Cell Res Ther 2025; 16:110. [PMID: 40038758 PMCID: PMC11881347 DOI: 10.1186/s13287-025-04191-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 01/24/2025] [Indexed: 03/06/2025] Open
Abstract
The tissue injury in maxillofacial region affects patients' physical function and specific mental health. This decade, utilizing regenerative medicine to achieve tissue regeneration has been proved a hopeful direction. Seed cells play a vital role in regeneration strategy. Among various kinds of stem cells that effectively to regenerate the soft and hard tissue of maxillofacial region, adipose-derived stem cells (ADSCs) have gained increasing interests of researchers due to their abundant sources, easy availability and multi-differentiation potentials in recent decades. Thus, this review focuses on the advances of ADSCs-based biomaterial in maxillofacial regeneration from the progress and strategies perspective. It is structured as introducing the properties of ADSCs, biomaterials (polymers, ceramics and metals) within ADSCs and the latest applications of ADSCs in maxillofacial regeneration, including temporomandibular joint (TMJ), bone, periodontal tissue, tooth, nerve as well as cosmetic field. In order to further facilitate ADSCs-based therapies as an emerging platform for regenerative medicine, this review also emphasized current challenges in translating ADSC-based therapies into clinical application and dissussed the strategies to solve these obstacles.
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Affiliation(s)
- Lijun Zhang
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Zihang Yu
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Shuchang Liu
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Fan Liu
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Shijie Zhou
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Yuanyuan Zhang
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China
| | - Yulou Tian
- Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Nanjing North Street 117, Shenyang, 110002, China.
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5
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Wang W, Wang Y, Gao L. Stem Cells Treatment for Subarachnoid Hemorrhage. Neurologist 2025; 30:80-86. [PMID: 39450602 DOI: 10.1097/nrl.0000000000000589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
BACKGROUND Subarachnoid hemorrhage (SAH) refers to bleeding in the subarachnoid space, which is a serious neurologic emergency. However, the treatment effects of SAH are limited. In recent years, stem cell (SC) therapy has gradually become a very promising therapeutic method and advanced scientific research area for SAH. REVIEW SUMMARY The SCs used for SAH treatment are mainly bone marrow mesenchymal stem cells (BMSCs), umbilical cord mesenchymal stem cells (hUC-MSCs), dental pulp stem cells (DPSCs), neural stem cells (NSCs)/neural progenitor cell (NPC), and endothelial progenitor cell (EPC). The mechanisms mainly included differentiation and migration of SCs for tissue repair; alleviating neuronal apoptosis; anti-inflammatory effects; and blood-brain barrier (BBB) protection. The dosage of SCs was generally 10 6 orders of magnitude. The administration methods included intravenous injection, nasal, occipital foramen magnum, and intraventricular administration. The administration time is generally 1 hour after SAH modeling, but it may be as late as 24 hours or 6 days. Existing studies have confirmed the neuroprotective effect of SCs in the treatment of SAH. CONCLUSIONS SC has great potential application value in SAH treatment, a few case reports have provided support for this. However, the relevant research is still insufficient and there is still a lack of clinical research on the SC treatment for SAH to further evaluate the effectiveness and safety before it can go from experiment to clinical application.
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Affiliation(s)
| | | | - Liansheng Gao
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Bondarenko NA, Surovtseva MA, Kim II, Ostapets SV, Kosareva OS, Drovosekov MN, Poveshchenko OV. Comparative Evaluation of the Functional Potential of Mesenchymal Stem Cells from the Bichat's Fat Pad, Bone Marrow, and Adipose Tissue for Bone Tissue Regeneration. Bull Exp Biol Med 2025; 178:581-585. [PMID: 40299120 DOI: 10.1007/s10517-025-06378-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Indexed: 04/30/2025]
Abstract
The functional potential of mesenchymal stem cells (MSC) isolated from Bichat's fat pad for osteoinduction in dentistry was compared with that of MSC from the adipose tissue and bone marrow. Functional activity of MSC was evaluated by the rate of their proliferation, migration, and differentiation into osteoblasts under the influence of erythropoietin. MSC from the Bichat's fat pad have higher proliferative activity than MSC from the adipose tissue or bone marrow under the influence of platelet-enriched plasma. Moreover, they are characterized by low migration activity, differentiate into osteoblasts, and intensively produce alkaline phosphatase under the influence of erythropoietin. The revealed functional potential of MSC from the Bichat's fat pad makes them promising for cell therapy, including osteoinduction in dentistry.
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Affiliation(s)
- N A Bondarenko
- Scientific Institution of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
| | - M A Surovtseva
- Scientific Institution of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
| | - I I Kim
- Scientific Institution of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
| | - S V Ostapets
- Novosibirsk State Medical University, Ministry of Health of the Russian Federation, Novosibirsk, Russia
| | - O S Kosareva
- Novosibirsk State Medical University, Ministry of Health of the Russian Federation, Novosibirsk, Russia
| | - M N Drovosekov
- Novosibirsk State Medical University, Ministry of Health of the Russian Federation, Novosibirsk, Russia
| | - O V Poveshchenko
- Scientific Institution of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
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7
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Jiang Y, Li Y, Duan L, Jiang B. Amniotic Fluid-Derived Stem Cells: An Overlooked Source of Stem Cells for Translational Research. DNA Cell Biol 2025; 44:144-152. [PMID: 40096350 DOI: 10.1089/dna.2024.0254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025] Open
Abstract
Amniotic fluid-derived stem cells (AFSCs) represent a promising yet underutilized resource for research and clinical applications. While AFSCs share phenotypic and functional characteristics with stem cells derived from somatic tissues such as bone marrow, adipose tissue, placenta, and umbilical cord, their unique developmental origin grants them several superior qualities. These include enhanced multipotency, tissue-specific genotypic profiles, and the ability to form single-cell colonies. Such features position AFSCs as highly valuable for translational research and tissue engineering. This review seeks to underscore the distinctive attributes of AFSCs, particularly their relevance in developmental research and engineering. By emphasizing these qualities, we aim to stimulate further exploration into their use in patient-specific induced pluripotent stem cells and organoid development, potentially unlocking their full therapeutic potential. The unique capabilities of AFSCs make them an exceptional candidate for advancing regenerative medicine, offering new avenues for treating a variety of conditions that currently have limited therapeutic options.
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Affiliation(s)
- Yu Jiang
- West China Second University Hosptial, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu, China
| | - Yanjiao Li
- Yunnan Key Laboratory for Basic Research on Bone and Joint Diseases, Kunming University, Kunming, China
| | - Li Duan
- Department of Orthopedics, Shenzhen Key Lab of Tissue Engineering, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
- Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen, Guangdong, China
| | - Bin Jiang
- Department of Orthopedics, Shenzhen Key Lab of Tissue Engineering, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
- R&D Division, Eureka Biotech Inc., Philadelphia, PA, USA
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8
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Wang X, Wang Q, Xia Z, Yang Y, Dai X, Zhang C, Wang J, Xu Y. Mesenchymal stromal cell therapies for traumatic neurological injuries. J Transl Med 2024; 22:1055. [PMID: 39578845 PMCID: PMC11583761 DOI: 10.1186/s12967-024-05725-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/01/2024] [Indexed: 11/24/2024] Open
Abstract
Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress.
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Affiliation(s)
- Xiujuan Wang
- Technology Department, Tianjin Everunion Biotechnology Co., Ltd, SOHO Nexus Center, No. 19A East 3rd Ring North Road, Chaoyang District, Beijing, 100020, China
| | - Qian Wang
- HELP Therapeutics Co., Ltd, No. 568 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu Province, China
- Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, E12 Avenida da Universidade, Macau, 519000, SAR, China
| | - Ziyao Xia
- Department of Ophthalmology, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Ying Yang
- Technology Department, Tianjin Everunion Biotechnology Co., Ltd, SOHO Nexus Center, No. 19A East 3rd Ring North Road, Chaoyang District, Beijing, 100020, China
| | - Xunan Dai
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China
| | - Chun Zhang
- Department of Ophthalmology, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
| | - Jiaxian Wang
- HELP Therapeutics Co., Ltd, No. 568 Longmian Avenue, Jiangning District, Nanjing, 211166, Jiangsu Province, China.
- Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, E12 Avenida da Universidade, Macau, 519000, SAR, China.
| | - Yongsheng Xu
- Technology Department, Tianjin Everunion Biotechnology Co., Ltd, SOHO Nexus Center, No. 19A East 3rd Ring North Road, Chaoyang District, Beijing, 100020, China.
- Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.
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He P, Yang Z, Li H, Zhou E, Hou Z, Sang H. miR-18a-5p promotes osteogenic differentiation of BMSC by inhibiting Notch2. Bone 2024; 188:117224. [PMID: 39117162 DOI: 10.1016/j.bone.2024.117224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 07/17/2024] [Accepted: 08/03/2024] [Indexed: 08/10/2024]
Abstract
Postmenopausal osteoporosis (PMOP) is a metabolic disorder characterized by the loss of bone density, which increases the risk of developing complications such as fractures. A pivotal factor contributing to the onset of PMOP is the diminished osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMSCs). MicroRNAs (miRNAs) play a substantial role in this process; however, their specific impact on regulating BMSCs osteogenesis remains unclear. Studies have evidenced a reduced expression of miR-18a-5p in PMOP, and concomitantly, our observations indicate an augmented expression of miR-18a-5p during the osteogenic differentiation of BMSCs. This investigation seeks to elucidate the regulatory influence of miR-18a-5p on BMSC osteogenic differentiation and the underlying mechanisms. In vitro experiments demonstrated that the overexpression of miR-18a-5p facilitated the osteogenic differentiation of BMSCs, while the downregulation of miR-18a-5p yielded converse outcomes. Mechanistically, We employed bioinformatics techniques to screen out the target gene Notch2 of miR-18a-5p. Subsequently, dual-luciferase reporter gene assays and rescue experiments substantiated that miR-18a-5p promotes BMSC osteogenic differentiation by suppressing Notch2. Finally, miR-18a-5p was overexpressed via adenovirus injection into the femoral bone marrow cavity, with results demonstrating its capability to enhance osteogenic differentiation and alleviate PMOP symptoms. Our findings disclose that miR-18a-5p fosters osteogenic differentiation of BMSC by inhibiting Notch2, thereby offering novel targets and strategies for PMOP treatment.
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Affiliation(s)
- Peipei He
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zefeng Yang
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Hetong Li
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Enhui Zhou
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zuoxu Hou
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hongxun Sang
- Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
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10
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Alessandri Bonetti M, Piccolo NS, Rubin JP, Egro FM. Fat Grafting and Regenerative Medicine in Burn Care. Clin Plast Surg 2024; 51:435-443. [PMID: 38789152 DOI: 10.1016/j.cps.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2024]
Abstract
Regenerative therapies such as fat grafting and Platelet Rich Plasma (PRP) have emerged as new options to tackle burn-related injuries and their long-term sequelae. Fat grafting is able to promote wound healing by regulating the inflammatory response, stimulating angiogenesis, favoring the remodeling of the extracellular matrix, and enhancing scar appearance. PRP can enhance wound healing by accelerating stages including hemostasis and re-epithelization. It can improve scar quality and complement fat grafting procedures. Their cost-effectiveness, minimal invasiveness, and promising results observed in the literature have made these tools as therapeutic candidates. The current evidence on fat grafting and PRP in acute and reconstructive burns is described and discussed in this study.
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Affiliation(s)
| | - Nelson S Piccolo
- Division of Plastic Surgery, Pronto Socorro Para Queimaduras, Brazil
| | - J Peter Rubin
- Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Francesco M Egro
- Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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11
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Arceri A, Mazzotti A, Artioli E, Zielli SO, Barile F, Manzetti M, Viroli G, Ruffilli A, Faldini C. Adipose-derived stem cells applied to ankle pathologies: a systematic review. Musculoskelet Surg 2024; 108:1-9. [PMID: 37943411 PMCID: PMC10881601 DOI: 10.1007/s12306-023-00798-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 10/09/2023] [Indexed: 11/10/2023]
Abstract
The purpose of this systematic review was to analyze the current use of adipose-derived mesenchymal stem cells (ADMSCs) and present the available evidence on their therapeutic potential in the treatment of ankle orthopedic issues, evaluating the applications and results. A literature search of PubMed, Google Scholar, EMBASE and Cochrane Library database was performed. The review was conducted following PRISMA guidelines. Risk of bias assessment was conducted through the Methodological Index for Non-Randomized Studies (MINORS) criteria. Initial search results yielded 4348 articles. A total of 8 articles were included in the review process. No clinical evidence has demonstrated the effectiveness of one isolation method over the other, but nonenzymatic mechanical method has more advantages. In all studies included significant clinical outcomes improvement were recorded in patients affected by osteochondral lesion and osteoarthritis of ankle. All studies performed a concomitant procedure. No serious complications were reported. ADMSC injection, especially through the nonenzymatic mechanical methods, looks to be simple and promising treatment for osteochondral lesions and osteoarthritis of the ankle, with no severe complications. The current scarcity of studies and their low-quality level preclude definitive conclusions presently. LEVEL OF EVIDENCE: III.
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Affiliation(s)
- A Arceri
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
| | - A Mazzotti
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40123, Bologna, Italy
| | - E Artioli
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
| | - S O Zielli
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy.
| | - F Barile
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40123, Bologna, Italy
| | - M Manzetti
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
| | - G Viroli
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
| | - A Ruffilli
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40123, Bologna, Italy
| | - C Faldini
- 1st Orthopaedics and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40123, Bologna, Italy
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12
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Sanie-Jahromi F, Nowroozzadeh MH, Shaabanian M, Khademi B, Owji N, Mehrabani D. Characterization of Central and Nasal Orbital Adipose Stem Cells and their Neural Differentiation Footprints. Curr Stem Cell Res Ther 2024; 19:1111-1119. [PMID: 37670706 DOI: 10.2174/1574888x19666230905114246] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 07/05/2023] [Accepted: 07/14/2023] [Indexed: 09/07/2023]
Abstract
BACKGROUND The unique potential of stem cells to restore vision and regenerate damaged ocular cells has led to the increased attraction of researchers and ophthalmologists to ocular regenerative medicine in recent decades. In addition, advantages such as easy access to ocular tissues, non-invasive follow-up, and ocular immunologic privilege have enhanced the desire to develop ocular regenerative medicine. OBJECTIVE This study aimed to characterize central and nasal orbital adipose stem cells (OASCs) and their neural differentiation potential. METHODS The central and nasal orbital adipose tissues extracted during an upper blepharoplasty surgery were explant-cultured in Dulbecco's Modified Eagle Medium (DMEM)/F12 supplemented with 10% fetal bovine serum (FBS). Cells from passage 3 were characterized morphologically by osteogenic and adipogenic differentiation potential and by flow cytometry for expression of mesenchymal (CD73, CD90, and CD105) and hematopoietic (CD34 and CD45) markers. The potential of OASCs for the expression of NGF, PI3K, and MAPK and to induce neurogenesis was assessed by real-time PCR. RESULTS OASCs were spindle-shaped and positive for adipogenic and osteogenic induction. They were also positive for mesenchymal and negative for hematopoietic markers. They were positive for NGF expression in the absence of any significant alteration in the expression of PI3K and MAPK genes. Nasal OASCs had higher expression of CD90, higher potential for adipogenesis, a higher level of NGF expression under serum-free supplementation, and more potential for neuron-like morphology. CONCLUSION We suggested the explant method of culture as an easy and suitable method for the expansion of OASCs. Our findings denote mesenchymal properties of both central and nasal OASCs, while mesenchymal and neural characteristics were expressed stronger in nasal OASCs when compared to central ones. These findings can be added to the literature when cell transplantation is targeted in the treatment of neuro-retinal degenerative disorders.
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Affiliation(s)
- Fatemeh Sanie-Jahromi
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M Hossein Nowroozzadeh
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mina Shaabanian
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Behzad Khademi
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Naser Owji
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Davood Mehrabani
- Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- University of Alberta, Edmonton, Alberta, Canada
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13
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Anastasio AT, Bagheri K, Adams SB. Contemporary Review: The Use of Adipocyte-Derived Mesenchymal Stem Cells in Pathologies of the Foot and Ankle. FOOT & ANKLE ORTHOPAEDICS 2023; 8:24730114231207643. [PMID: 37929076 PMCID: PMC10623921 DOI: 10.1177/24730114231207643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023] Open
Affiliation(s)
| | - Kian Bagheri
- Department of Orthopedic Surgery, Duke University Hospital, Durham, NC, USA
- Campbell University School of Osteopathic Medicine, Lillington, NC, USA
| | - Samuel B. Adams
- Department of Orthopedic Surgery, Duke University Hospital, Durham, NC, USA
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14
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Imaizumi T, Hayashi R, Kudo Y, Li X, Yamaguchi K, Shibata S, Okubo T, Ishii T, Honma Y, Nishida K. Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function. Sci Rep 2023; 13:13100. [PMID: 37567940 PMCID: PMC10421917 DOI: 10.1038/s41598-023-40136-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 08/05/2023] [Indexed: 08/13/2023] Open
Abstract
Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren's syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.
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Affiliation(s)
- Tsutomu Imaizumi
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Ryuhei Hayashi
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
- Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Osaka, 565-0871, Japan.
| | - Yuji Kudo
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Xiaoqin Li
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
| | - Kaito Yamaguchi
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Shun Shibata
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
- Department of Informative Genetics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan
| | - Toru Okubo
- Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Tsuyoshi Ishii
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Yoichi Honma
- Basic Research Development Division, ROHTO Pharmaceutical, Ikuno-ku, Osaka, 544-8666, Japan
| | - Kohji Nishida
- Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
- Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Osaka, 565-0871, Japan.
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15
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Lim YC, Jung JI, Hong IK. A Novel Method for Human Adipose-Derived Stem Cell Isolation and Cryopreservation. Cell Reprogram 2023; 25:171-179. [PMID: 37590008 DOI: 10.1089/cell.2023.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023] Open
Abstract
Adipose-derived stem cells (ADSCs) are isolated from abundant adipose tissue and have the capacity to differentiate into multiple cell lineages. ADSCs have raised big interest in therapeutic applications in regenerative medicine and demonstrated to fulfill the criteria for a successful cell therapy. There are several methods for isolation of ADSCs from adipose tissue and cryopreservation of ADSCs. Here, novel methods for the isolation and cryopreservation of ADSCs are presented and focused. Microscopic pieces of adipose tissue were placed on transwell inserts, and the ADSCs were induced to migrate to the lower wells for 1 week. We compared the properties of our ADSCs with those isolated by enzymatic digestion and enzyme-free method of culture plate, and our ADSCs were found to be more stable and healthier. In addition, we proposed a novel cryoprotectant solution (FNCP) containing pectin and L-alanine, which was compared with standard cryoprotectant solution. Overall, our methods proved more useful for ADSCs isolation than other methods and did not require consideration of "minimal manipulation" by the U.S. Food and Drug Administration (FDA). Furthermore, our FNCP did not contain dimethyl sulfoxide and fetal bovine serum, therefore stable storage is possible in xeno-free and animal-free cryopreservation solutions.
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Affiliation(s)
- Young-Cheol Lim
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
| | - Jung-Il Jung
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
| | - In-Kee Hong
- Bio Lab. Efficacy Research Team, Frombio. Co., Ltd, Yongin-si, Republic of Korea
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16
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Woodbury SM, Swanson WB, Mishina Y. Mechanobiology-informed biomaterial and tissue engineering strategies for influencing skeletal stem and progenitor cell fate. Front Physiol 2023; 14:1220555. [PMID: 37520820 PMCID: PMC10373313 DOI: 10.3389/fphys.2023.1220555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/05/2023] [Indexed: 08/01/2023] Open
Abstract
Skeletal stem and progenitor cells (SSPCs) are the multi-potent, self-renewing cell lineages that form the hematopoietic environment and adventitial structures of the skeletal tissues. Skeletal tissues are responsible for a diverse range of physiological functions because of the extensive differentiation potential of SSPCs. The differentiation fates of SSPCs are shaped by the physical properties of their surrounding microenvironment and the mechanical loading forces exerted on them within the skeletal system. In this context, the present review first highlights important biomolecules involved with the mechanobiology of how SSPCs sense and transduce these physical signals. The review then shifts focus towards how the static and dynamic physical properties of microenvironments direct the biological fates of SSPCs, specifically within biomaterial and tissue engineering systems. Biomaterial constructs possess designable, quantifiable physical properties that enable the growth of cells in controlled physical environments both in-vitro and in-vivo. The utilization of biomaterials in tissue engineering systems provides a valuable platform for controllably directing the fates of SSPCs with physical signals as a tool for mechanobiology investigations and as a template for guiding skeletal tissue regeneration. It is paramount to study this mechanobiology and account for these mechanics-mediated behaviors to develop next-generation tissue engineering therapies that synergistically combine physical and chemical signals to direct cell fate. Ultimately, taking advantage of the evolved mechanobiology of SSPCs with customizable biomaterial constructs presents a powerful method to predictably guide bone and skeletal organ regeneration.
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Affiliation(s)
- Seth M. Woodbury
- Yuji Mishina Laboratory, University of Michigan School of Dentistry, Department of Biologic and Materials Science & Prosthodontics, Ann Arbor, MI, United States
- University of Michigan College of Literature, Science, and Arts, Department of Chemistry, Ann Arbor, MI, United States
- University of Michigan College of Literature, Science, and Arts, Department of Physics, Ann Arbor, MI, United States
| | - W. Benton Swanson
- Yuji Mishina Laboratory, University of Michigan School of Dentistry, Department of Biologic and Materials Science & Prosthodontics, Ann Arbor, MI, United States
| | - Yuji Mishina
- Yuji Mishina Laboratory, University of Michigan School of Dentistry, Department of Biologic and Materials Science & Prosthodontics, Ann Arbor, MI, United States
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17
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Subayyil AA, Basmaeil YS, Kulayb HB, Alrodayyan M, Alhaber LAA, Almanaa TN, Khatlani T. Preconditioned Chorionic Villus Mesenchymal Stem/Stromal Cells (CVMSCs) Minimize the Invasive Phenotypes of Breast Cancer Cell Line MDA231 In Vitro. Int J Mol Sci 2023; 24:ijms24119569. [PMID: 37298519 DOI: 10.3390/ijms24119569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 03/30/2023] [Accepted: 04/03/2023] [Indexed: 06/12/2023] Open
Abstract
Among the newer choices of targeted therapies against cancer, stem cell therapy is gaining importance because of their antitumor properties. Stem cells suppress growth, metastasis, and angiogenesis, and induce apoptosis in cancer cells. In this study, we have examined the impact of the cellular component and the secretome of preconditioned and naïve placenta-derived Chorionic Villus Mesenchymal Stem Cells (CVMSCs) on the functional characteristics of the Human Breast Cancer cell line MDA231. MDA231 cells were treated with preconditioned CVMSCs and their conditioned media (CM), followed by an evaluation of their functional activities and modulation in gene and protein expression. Human Mammary Epithelial Cells (HMECs) were used as a control. CM obtained from the preconditioned CVMSCs significantly altered the proliferation of MDA231 cells, yet no change in other phenotypes, such as adhesion, migration, and invasion, were observed at various concentrations and time points tested. However, the cellular component of preconditioned CVMSCs significantly inhibited several phenotypes of MDA231 cells, including proliferation, migration, and invasion. CVMSCs-treated MDA231 cells exhibited modulation in the expression of various genes involved in apoptosis, oncogenesis, and Epithelial to Mesenchymal Transition (EMT), explaining the changes in the invasive behavior of MDA231 cells. These studies reveal that preconditioned CVMSCs may make useful candidate in a stem cell-based therapy against cancer.
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Affiliation(s)
- Abdullah Al Subayyil
- Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia
| | - Yasser S Basmaeil
- Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia
| | - Hayaa Bin Kulayb
- Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia
| | - Maha Alrodayyan
- Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia
| | - Lama Abdulaziz A Alhaber
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Taghreed N Almanaa
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Tanvir Khatlani
- Blood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences (KSAU), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia
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18
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Coelho HRS, Neves SCD, da Silva Menezes JN, Antoniolli-Silva ACMB, Oliveira RJ. Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial. Stem Cell Res Ther 2023; 14:64. [PMID: 37016455 PMCID: PMC10074857 DOI: 10.1186/s13287-023-03294-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 03/17/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Detrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men. METHODS Nine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone. RESULTS Cell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day. CONCLUSIONS The results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity. Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021-Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398.
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Affiliation(s)
- Henrique Rodrigues Scherer Coelho
- Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
- Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
| | - Silvia Cordeiro das Neves
- Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
- Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
| | | | - Andréia Conceição Milan Brochado Antoniolli-Silva
- Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
- Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil
| | - Rodrigo Juliano Oliveira
- Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica (CeTroGen), Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil.
- Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina (FAMED), Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil.
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19
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Liu M, Cheng L, Li X, Wang H, Wang M, Gan L. Resveratrol Reverses Myogenic Induction Suppression Caused by High Glucose Through Activating the SIRT1/AKT/FOXO1 Pathway. Nat Prod Commun 2023. [DOI: 10.1177/1934578x231159722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023] Open
Abstract
Background Differentiated bone marrow mesenchymal stem cells (BMSCs) may be a therapeutic strategy to treat sarcopenia caused by high glucose. The effects of resveratrol in the myogenic induction of BMSCs under high glucose are unknown. We evaluated the effects and possible mechanisms of high glucose and resveratrol on myogenic induction of rat BMSCs. Methods Primary rat BMSCs were isolated and purified from Sprague-Dawley rats aged between 3 and 4 weeks. Rat BMSCs were differentiated into myogenic cells using conditioned medium and treated with glucose and/or resveratrol along with EX527 (a specific silent information regulator 1 [SIRT1] inhibitor). The expressions of MyoD1 and Myogenin were measured. The reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity, and the expressions of FOXO1 and p-AKT/AKT during myogenic induction were also examined. Results High glucose decreased cell viability, cell proliferation, and SOD activity, increased intracellular ROS levels, and inhibited the AKT/FOXO1. Resveratrol reversed myogenic induction suppression caused by high glucose, partly through restoring cell proliferation and viability, reducing peroxidative damage, and activating the AKT/FOXO1 pathway; this effect was eliminated by EX527. Conclusion Our results indicate that resveratrol promoted myogenic induction and partially reversed the suppression of myogenic induction caused by high glucose through activating the SIRT1/AKT/FOXO1 pathway.
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Affiliation(s)
- Meiling Liu
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Luyang Cheng
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xianglu Li
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hongzhi Wang
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Manfeng Wang
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lu Gan
- Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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20
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An Overview on Wound Dressings and Sutures Fabricated by Electrospinning. BIOTECHNOL BIOPROC E 2023. [DOI: 10.1007/s12257-021-0364-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
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Microbiological Aspects of Pharmaceutical Manufacturing of Adipose-Derived Stem Cell-Based Medicinal Products. Cells 2023; 12:cells12050680. [PMID: 36899816 PMCID: PMC10000438 DOI: 10.3390/cells12050680] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/08/2023] [Accepted: 02/14/2023] [Indexed: 02/24/2023] Open
Abstract
Subcutaneous adipose tissue is an excellent source of mesenchymal stem cells (ADSCs), which can be used in cell therapies as an active substance in advanced therapy medicinal products (ATMPs). Because of the short shelf-life of ATMPs and the time needed to obtain the results of microbiological analysis, the final product is often administered to the patient before sterility is confirmed. Because the tissue used for cell isolation is not sterilized to maintain cell viability, controlling and ensuring microbiological purity at all stages of production is crucial. This study presents the results of monitoring the contamination incidence during ADSC-based ATMP manufacturing over two years. It was found that more than 40% of lipoaspirates were contaminated with thirteen different microorganisms, which were identified as being physiological flora from human skin. Such contamination was successfully eliminated from the final ATMPs through the implementation of additional microbiological monitoring and decontamination steps at various stages of production. Environmental monitoring revealed incidental bacterial or fungal growth, which did not result in any product contamination and was reduced thanks to an effective quality assurance system. To conclude, the tissue used for ADSC-based ATMP manufacturing should be considered contaminated; therefore, good manufacturing practices specific to this type of product must be elaborated and implemented by the manufacturer and the clinic in order to obtain a sterile product.
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Zhang C, Wang G, Lin H, Shang Y, Liu N, Zhen Y, An Y. Cartilage 3D bioprinting for rhinoplasty using adipose-derived stem cells as seed cells: Review and recent advances. Cell Prolif 2023; 56:e13417. [PMID: 36775884 PMCID: PMC10068946 DOI: 10.1111/cpr.13417] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 01/10/2023] [Accepted: 01/18/2023] [Indexed: 02/14/2023] Open
Abstract
Nasal deformities due to various causes affect the aesthetics and use of the nose, in which case rhinoplasty is necessary. However, the lack of cartilage for grafting has been a major problem and tissue engineering seems to be a promising solution. 3D bioprinting has become one of the most advanced tissue engineering methods. To construct ideal cartilage, bio-ink, seed cells, growth factors and other methods to promote chondrogenesis should be considered and weighed carefully. With continuous progress in the field, bio-ink choices are becoming increasingly abundant, from a single hydrogel to a combination of hydrogels with various characteristics, and more 3D bioprinting methods are also emerging. Adipose-derived stem cells (ADSCs) have become one of the most popular seed cells in cartilage 3D bioprinting, owing to their abundance, excellent proliferative potential, minimal morbidity during harvest and lack of ethical considerations limitations. In addition, the co-culture of ADSCs and chondrocytes is commonly used to achieve better chondrogenesis. To promote chondrogenic differentiation of ADSCs and construct ideal highly bionic tissue-engineered cartilage, researchers have used a variety of methods, including adding appropriate growth factors, applying biomechanical stimuli and reducing oxygen tension. According to the process and sequence of cartilage 3D bioprinting, this review summarizes and discusses the selection of hydrogel and seed cells (centered on ADSCs), the design of printing, and methods for inducing the chondrogenesis of ADSCs.
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Affiliation(s)
- Chong Zhang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Guanhuier Wang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Hongying Lin
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Yujia Shang
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China.,Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
| | - Na Liu
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China.,Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
| | - Yonghuan Zhen
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
| | - Yang An
- Department of Plastic Surgery, Peking University Third Hospital, Beijing, China
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23
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Najera J, Hao J. Recent advance in mesenchymal stem cells therapy for atopic dermatitis. J Cell Biochem 2023; 124:181-187. [PMID: 36576973 DOI: 10.1002/jcb.30365] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 11/07/2022] [Accepted: 12/19/2022] [Indexed: 12/29/2022]
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells found in a variety of tissues in the body, including but not limited to bone marrow, adipose tissue, umbilical cord, and umbilical cord blood. Given their immunomodulatory effect and ability to be readily isolated from several tissues, they have great potential to be used as a therapeutic agent in a variety of immune-mediated disorders. Atopic dermatitis (AD) is a persistent and relapsing immune skin condition that has recently become more common in several species such as humans, canines, equines, and felines. The use of MSCs to treat AD has piqued the great interest of researchers in recent years. In this article, we review the recent understanding of AD pathology and advances in preclinical and clinical studies of MSCs, MSCs-derived conditional media and exosomes as therapeutic tools to treat AD.
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Affiliation(s)
- Jonathan Najera
- College of Veterinary Medicine, Western University of Health Sciences, Pomona, California, USA.,Department of Biology, College of Science, California State University Polytechnic University, Pomona, California, USA
| | - Jijun Hao
- College of Veterinary Medicine, Western University of Health Sciences, Pomona, California, USA
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24
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Alqahtani S, Butcher MC, Ramage G, Dalby MJ, McLean W, Nile CJ. Acetylcholine Receptors in Mesenchymal Stem Cells. Stem Cells Dev 2023; 32:47-59. [PMID: 36355611 DOI: 10.1089/scd.2022.0201] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are well known for their regenerative potential. Even though the ability of MSCs to proliferate and differentiate has been studied extensively, there remains much to learn about the signaling mechanisms and pathways that control proliferation and influence the differentiation phenotype. In recent years, there has been growing evidence for the utility of non-neuronal cholinergic signaling systems and that acetylcholine (ACh) plays an important ubiquitous role in cell-to-cell communication. Indeed, cholinergic signaling is hypothesized to occur in stem cells and ACh synthesis, as well as in ACh receptor (AChR) expression, has been identified in several stem cell populations, including MSCs. Furthermore, AChRs have been found to influence MSC regenerative potential. In humans, there are two major classes of AChRs, muscarinic AChRs and nicotinic AChRs, with each class possessing several subtypes or subunits. In this review, the expression and function of AChRs in different types of MSC are summarized with the aim of highlighting how AChRs play a pivotal role in regulating MSC regenerative function.
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Affiliation(s)
- Saeed Alqahtani
- School of Medicine Dentistry and Nursing and University of Glasgow, Glasgow, United Kingdom
| | - Mark C Butcher
- School of Medicine Dentistry and Nursing and University of Glasgow, Glasgow, United Kingdom
| | - Gordon Ramage
- School of Medicine Dentistry and Nursing and University of Glasgow, Glasgow, United Kingdom
| | - Matthew J Dalby
- School of Molecular Biosciences, University of Glasgow, Glasgow, United Kingdom
| | - William McLean
- School of Medicine Dentistry and Nursing and University of Glasgow, Glasgow, United Kingdom
| | - Christopher J Nile
- Faculty of Medical Sciences, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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25
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Mesoporous Silica Promotes Osteogenesis of Human Adipose-Derived Stem Cells Identified by a High-Throughput Microfluidic Chip Assay. Pharmaceutics 2022; 14:pharmaceutics14122730. [PMID: 36559224 PMCID: PMC9781822 DOI: 10.3390/pharmaceutics14122730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/02/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Silicon-derived biomaterials are conducive to regulating the fate of osteo-related stem cells, while their effects on the osteogenic differentiation of human adipose-derived stem cells (hADSCs) remain inconclusive. Mesoporous silica (mSiO2) is synthesized in a facile route that exhibited the capability of promoting osteogenic differentiation of hADSCs. The metabolism of SiO2 in cells is proposed according to the colocalization fluorescence analysis between lysosomes and nanoparticles. The released silicon elements promote osteogenic differentiation. The detection of secretory proteins through numerous parallel experiments performed via a microfluidic chip confirms the positive effect of SiO2 on the osteogenic differentiation of hADSCs. Moreover, constructed with superparamagnetic iron oxide (Fe3O4), the magnetic nanoparticles (MNPs) of Fe3O4@mSiO2 endow the cells with magnetic resonance imaging (MRI) properties. The MNP-regulated osteogenic differentiation of autologous adipose-derived stem cells provides considerable clinical application prospects for stem cell therapy of bone tissue repair with an effective reduction in immune rejection.
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26
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Zhao C, Liu S, Gao F, Zou Y, Ren Z, Yu Z. The role of tumor microenvironment reprogramming in primary liver cancer chemotherapy resistance. Front Oncol 2022; 12:1008902. [PMID: 36505831 PMCID: PMC9731808 DOI: 10.3389/fonc.2022.1008902] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/01/2022] [Indexed: 11/25/2022] Open
Abstract
Primary liver cancer (PLC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), and other rare tumours, is the second leading cause of cancer-related mortality. It has been a major contributor to the cancer burden worldwide. Of all primary liver cancer, HCC is the most common type. Over the past few decades, chemotherapy, immunotherapy and other therapies have been identified as applicable to the treatment of HCC. However, evidence suggests that chemotherapy resistance is associated with higher mortality rates in liver cancer. The tumour microenvironment (TME), which includes molecular, cellular, extracellular matrix(ECM), and vascular signalling pathways, is a complex ecosystem. It is now increasingly recognized that the tumour microenvironment plays a pivotal role in PLC prognosis, progression and treatment response. Cancer cells reprogram the tumour microenvironment to develop resistance to chemotherapy drugs distinct from normal differentiated tissues. Chemotherapy resistance mechanisms are reshaped during TME reprogramming. For this reason, TME reprogramming can provide a powerful tool to understand better both cancer-fate processes and regenerative, with the potential to develop a new treatment. This review discusses the recent progress of tumour drug resistance, particularly tumour microenvironment reprogramming in tumour chemotherapy resistance, and focuses on its potential application prospects.
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Affiliation(s)
- Chunyu Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shanshuo Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Gao
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yawen Zou
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zujiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province; Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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El-Husseiny HM, Mady EA, Helal MAY, Tanaka R. The Pivotal Role of Stem Cells in Veterinary Regenerative Medicine and Tissue Engineering. Vet Sci 2022; 9:648. [PMID: 36423096 PMCID: PMC9698002 DOI: 10.3390/vetsci9110648] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/09/2022] [Accepted: 11/18/2022] [Indexed: 07/30/2023] Open
Abstract
The introduction of new regenerative therapeutic modalities in the veterinary practice has recently picked up a lot of interest. Stem cells are undifferentiated cells with a high capacity to self-renew and develop into tissue cells with specific roles. Hence, they are an effective therapeutic option to ameliorate the ability of the body to repair and engineer damaged tissues. Currently, based on their facile isolation and culture procedures and the absence of ethical concerns with their use, mesenchymal stem cells (MSCs) are the most promising stem cell type for therapeutic applications. They are becoming more and more well-known in veterinary medicine because of their exceptional immunomodulatory capabilities. However, their implementation on the clinical scale is still challenging. These limitations to their use in diverse affections in different animals drive the advancement of these therapies. In the present article, we discuss the ability of MSCs as a potent therapeutic modality for the engineering of different animals' tissues including the heart, skin, digestive system (mouth, teeth, gastrointestinal tract, and liver), musculoskeletal system (tendons, ligaments, joints, muscles, and nerves), kidneys, respiratory system, and eyes based on the existing knowledge. Moreover, we highlighted the promises of the implementation of MSCs in clinical use in veterinary practice.
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Affiliation(s)
- Hussein M. El-Husseiny
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
- Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Eman A. Mady
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
- Department of Animal Hygiene, Behavior and Management, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Mahmoud A. Y. Helal
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
- Department of Animal Medicine, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Ryou Tanaka
- Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi 183-8509, Tokyo, Japan
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López-Ornelas A, Jiménez A, Pérez-Sánchez G, Rodríguez-Pérez CE, Corzo-Cruz A, Velasco I, Estudillo E. The Impairment of Blood-Brain Barrier in Alzheimer's Disease: Challenges and Opportunities with Stem Cells. Int J Mol Sci 2022; 23:ijms231710136. [PMID: 36077533 PMCID: PMC9456198 DOI: 10.3390/ijms231710136] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/28/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disorder and its prevalence is increasing. Nowadays, very few drugs effectively reduce AD symptoms and thus, a better understanding of its pathophysiology is vital to design new effective schemes. Presymptomatic neuronal damage caused by the accumulation of Amyloid β peptide and Tau protein abnormalities remains a challenge, despite recent efforts in drug development. Importantly, therapeutic targets, biomarkers, and diagnostic techniques have emerged to detect and treat AD. Of note, the compromised blood-brain barrier (BBB) and peripheral inflammation in AD are becoming more evident, being harmful factors that contribute to the development of the disease. Perspectives from different pre-clinical and clinical studies link peripheral inflammation with the onset and progression of AD. This review aims to analyze the main factors and the contribution of impaired BBB in AD development. Additionally, we describe the potential therapeutic strategies using stem cells for AD treatment.
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Affiliation(s)
- Adolfo López-Ornelas
- División de Investigación, Hospital Juárez de México, Mexico City 07760, Mexico
- Hospital Nacional Homeopático, Hospitales Federales de Referencia, Mexico City 06800, Mexico
| | - Adriana Jiménez
- División de Investigación, Hospital Juárez de México, Mexico City 07760, Mexico
| | - Gilberto Pérez-Sánchez
- Laboratorio de Psicoinmunología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Colonia San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico
| | - Citlali Ekaterina Rodríguez-Pérez
- Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - Alejandro Corzo-Cruz
- Laboratorio Traslacional, Escuela Militar de Graduados de Sanidad, Secretaría de la Defensa Nacional, Batalla de Celaya 202, Lomas de Sotelo, Miguel Hidalgo, Ciudad de México 11200, Mexico
| | - Iván Velasco
- Instituto de Fisiología Celular—Neurociencias, Universidad Nacional Autónoma de Mexico, Mexico City 04510, Mexico
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
| | - Enrique Estudillo
- Laboratorio de Reprogramación Celular, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico
- Correspondence:
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29
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Zhang Y, Le X, Zheng S, Zhang K, He J, Liu M, Tu C, Rao W, Du H, Ouyang Y, Li C, Wu D. MicroRNA-146a-5p-modified human umbilical cord mesenchymal stem cells enhance protection against diabetic nephropathy in rats through facilitating M2 macrophage polarization. Stem Cell Res Ther 2022; 13:171. [PMID: 35477552 PMCID: PMC9044847 DOI: 10.1186/s13287-022-02855-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/12/2021] [Indexed: 12/13/2022] Open
Abstract
Background Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and a common cause of end-stage renal disease (ESRD). Mesenchymal stem cells (MSCs) possess potent anti-inflammatory and immunomodulatory properties, which render them an attractive therapeutic tool for tissue damage and inflammation. Methods This study was designed to determine the protective effects and underlying mechanisms of human umbilical cord-derived MSCs (UC-MSCs) on streptozotocin-induced DN. Renal function and histological staining were used to evaluate kidney damage. RNA high-throughput sequencing on rat kidney and UCMSC-derived exosomes was used to identify the critical miRNAs. Co-cultivation of macrophage cell lines and UC-MSCs-derived conditional medium were used to assess the involvement of macrophage polarization signaling. Results UC-MSC administration significantly improved renal function, reduced the local and systemic inflammatory cytokine levels, and attenuated inflammatory cell infiltration into the kidney tissue in DN rats. Moreover, UC-MSCs shifted macrophage polarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. Mechanistically, miR-146a-5p was significantly downregulated and negatively correlated with renal injury in DN rats as determined through high-throughput RNA sequencing. Importantly, UC-MSCs-derived miR-146a-5p promoted M2 macrophage polarization by inhibiting tumor necrosis factor receptor-associated factor-6 (TRAF6)/signal transducer and activator of transcription (STAT1) signaling pathway. Furthermore, miR-146a-5p modification in UC-MSCs enhanced the efficacy of anti-inflammation and renal function improvement. Conclusions Collectively, our findings demonstrate that UC-MSCs-derived miR-146a-5p have the potential to restore renal function in DN rats through facilitating M2 macrophage polarization by targeting TRAF6. This would pave the way for the use of miRNA-modified cell therapy for kidney diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02855-7.
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Affiliation(s)
- Yaqi Zhang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Xi Le
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Shuo Zheng
- Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China
| | - Ke Zhang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Jing He
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Mengting Liu
- Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China
| | - Chengshu Tu
- Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China
| | - Wei Rao
- Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China
| | - Hongyuan Du
- Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China
| | - Yu Ouyang
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China
| | - Changyong Li
- Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
| | - Dongcheng Wu
- Department of Biochemistry and Molecular Biology, Wuhan University School of Basic Medical Sciences, Wuhan, China. .,Wuhan Hamilton Biotechnology Co., Ltd., Wuhan, China. .,Guangzhou Hamilton Biotechnology Co., Ltd, Wuhan, China.
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30
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Ababneh NA, Al-Kurdi B, Jamali F, Awidi A. A comparative study of the capability of MSCs isolated from different human tissue sources to differentiate into neuronal stem cells and dopaminergic-like cells. PeerJ 2022; 10:e13003. [PMID: 35341051 PMCID: PMC8944334 DOI: 10.7717/peerj.13003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/03/2022] [Indexed: 01/11/2023] Open
Abstract
Background Neurodegenerative diseases are characterized by progressive neuronal loss and degeneration. The regeneration of neurons is minimal and neurogenesis is limited only to specific parts of the brain. Several clinical trials have been conducted using Mesenchymal Stem Cells (MSCs) from different sources to establish their safety and efficacy for the treatment of several neurological disorders such as Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Aim The aim of this study was to provide a comparative view of the capabilities of MSCs, isolated from different human tissue sources to differentiate into neuronal stem cell-like cells (NSCs) and possibly into dopaminergic neural- like cells. Methods Mesenchymal stem cells were isolated from human bone marrow, adipose, and Wharton's jelly (WJ) tissue samples. Cells were characterized by flow cytometry for their ability to express the most common MSC markers. The differentiation potential was also assessed by differentiating them into osteogenic and adipogenic cell lineages. To evaluate the capacity of these cells to differentiate towards the neural stem cell-like lineage, cells were cultured in media containing small molecules. Cells were utilized for gene expression and immunofluorescence analysis at different time points. Results Our results indicate that we have successfully isolated MSCs from bone marrow, adipose tissue, and Wharton's jelly. WJ-MSCs showed a slightly higher proliferation rate after 72 hours compared to BM and AT derived MSCs. Gene expression of early neural stem cell markers revealed that WJ-MSCs had higher expression of Nestin and PAX6 compared to BM and AT-MSCs, in addition to LMX expression as an early dopaminergic neural marker. Immunofluorescence analysis also revealed that these cells successfully expressed SOX1, SOX2, Nestin, TUJ1, FOXA2 and TH. Conclusion These results indicate that the protocol utilized has successfully differentiated BM, AT and WJ-MSCs into NSC-like cells. WJ-MSCs possess a higher potential to transdifferentiate into NSC and dopaminergic-like cells. Thus, it might indicate that this protocol can be used to induce MSC into neuronal lineage, which provides an additional or alternative source of cells to be used in the neurological cell-based therapies.
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Affiliation(s)
- Nidaa A. Ababneh
- Cell Therapy Center (CTC), the University of Jordan, Amman, Jordan
| | - Ban Al-Kurdi
- Cell Therapy Center (CTC), the University of Jordan, Amman, Jordan
| | - Fatima Jamali
- Cell Therapy Center (CTC), the University of Jordan, Amman, Jordan
| | - Abdalla Awidi
- Cell Therapy Center (CTC), the University of Jordan, Amman, Jordan,Hemostasis and Thrombosis Laboratory, School of Medicine, the University of Jordan, Amman, Jordan,Department of Hematology and Oncology, Jordan University Hospital, Amman, Jordan
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31
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Mesenchymal stem cell (MSC)-derived exosomes as novel vehicles for delivery of miRNAs in cancer therapy. Cancer Gene Ther 2022; 29:1105-1116. [PMID: 35082400 DOI: 10.1038/s41417-022-00427-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/11/2021] [Accepted: 01/14/2022] [Indexed: 12/15/2022]
Abstract
Mesenchymal stem cells (MSCs) are known as promising sources for cancer therapy and can be utilized as vehicles in cancer gene therapy. MSC-derived exosomes are central mediators in the therapeutic functions of MSCs, known as the novel cell-free alternatives to MSC-based cell therapy. MSC-derived exosomes show advantages including higher safety as well as more stability and convenience for storage, transport and administration compared to MSCs transplant therapy. Unmodified MSC-derived exosomes can promote or inhibit tumors while modified MSC-derived exosomes are involved in the suppression of cancer development and progression via the delivery of several therapeutics molecules including chemotherapeutic drugs, miRNAs, anti-miRNAs, specific siRNAs, and suicide gene mRNAs. In most malignancies, dysregulation of miRNAs not only occurs as a consequence of cancer progression but also is directly involved during tumor initiation and development due to their roles as oncogenes (oncomiRs) or tumor suppressors (TS-miRNAs). MiRNA restoration is usually achieved by overexpression of TS-miRNAs using synthetic miRNA mimics and viral vectors or even downregulation of oncomiRs using anti-miRNAs. Similar to other therapeutic molecules, the efficacy of miRNAs restoration in cancer therapy depends on the effectiveness of the delivery system. In the present review, we first provided an overview of the properties and potentials of MSCs in cancer therapy as well as the application of MSC-derived exosomes in cancer therapy. Finally, we specifically focused on harnessing the MSC-derived exosomes for the aim of miRNA delivery in cancer therapy.
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Cardiomyogenic Differentiation Potential of Human Dilated Myocardium-Derived Mesenchymal Stem/Stromal Cells: The Impact of HDAC Inhibitor SAHA and Biomimetic Matrices. Int J Mol Sci 2021; 22:ijms222312702. [PMID: 34884505 PMCID: PMC8657551 DOI: 10.3390/ijms222312702] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 12/21/2022] Open
Abstract
Dilated cardiomyopathy (DCM) is the most common type of nonischemic cardiomyopathy characterized by left ventricular or biventricular dilation and impaired contraction leading to heart failure and even patients’ death. Therefore, it is important to search for new cardiac tissue regenerating tools. Human mesenchymal stem/stromal cells (hmMSCs) were isolated from post-surgery healthy and DCM myocardial biopsies and their differentiation to the cardiomyogenic direction has been investigated in vitro. Dilated hmMSCs were slightly bigger in size, grew slower, but had almost the same levels of MSC-typical surface markers as healthy hmMSCs. Histone deacetylase (HDAC) activity in dilated hmMSCs was 1.5-fold higher than in healthy ones, which was suppressed by class I and II HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) showing activation of cardiomyogenic differentiation-related genes alpha-cardiac actin (ACTC1) and cardiac troponin T (TNNT2). Both types of hmMSCs cultivated on collagen I hydrogels with hyaluronic acid (HA) or 2-methacryloyloxyethyl phosphorylcholine (MPC) and exposed to SAHA significantly downregulated focal adhesion kinase (PTK2) and activated ACTC1 and TNNT2. Longitudinal cultivation of dilated hmMSC also upregulated alpha-cardiac actin. Thus, HDAC inhibitor SAHA, in combination with collagen I-based hydrogels, can tilt the dilated myocardium hmMSC toward cardiomyogenic direction in vitro with further possible therapeutic application in vivo.
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Sharma S, Muthu S, Jeyaraman M, Ranjan R, Jha SK. Translational products of adipose tissue-derived mesenchymal stem cells: Bench to bedside applications. World J Stem Cells 2021; 13:1360-1381. [PMID: 34786149 PMCID: PMC8567449 DOI: 10.4252/wjsc.v13.i10.1360] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/02/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With developments in the field of tissue engineering and regenerative medicine, the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians. Among all the available biological tissues, research and exploration of adipose tissue have become more robust. Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential. The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth, proliferation, and differentiation. Adipose tissue, apart from being the powerhouse of energy storage, also functions as the largest endocrine organ, with the release of various adipokines. The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues. The results of adipose-derived stem-cell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis, fat graft integration, and survival within the recipient tissue and promote the regeneration of tissue are promising. Adipose tissue gives rise to various by-products upon processing. This article highlights the significance and the usage of various adipose tissue by-products, their individual characteristics, and their clinical applications.
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Affiliation(s)
- Shilpa Sharma
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
| | - Sathish Muthu
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu 624304, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group, Lucknow, Uttar Pradesh 226010, India
- Research Scholar, Department of Biotechnology, School of Engineering and Technology, Greater Noida, Sharda University, Uttar Pradesh 201306, India
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India.
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh 201306, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh 201306, India
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Pant T, Juric M, Bosnjak ZJ, Dhanasekaran A. Recent Insight on the Non-coding RNAs in Mesenchymal Stem Cell-Derived Exosomes: Regulatory and Therapeutic Role in Regenerative Medicine and Tissue Engineering. Front Cardiovasc Med 2021; 8:737512. [PMID: 34660740 PMCID: PMC8517144 DOI: 10.3389/fcvm.2021.737512] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/06/2021] [Indexed: 12/13/2022] Open
Abstract
Advances in the field of regenerative medicine and tissue engineering over the past few decades have paved the path for cell-free therapy. Numerous stem cell types, including mesenchymal stem cells (MSCs), have been reported to impart therapeutic effects via paracrine secretion of exosomes. The underlying factors and the associated mechanisms contributing to these MSC-derived exosomes' protective effects are, however, poorly understood, limiting their application in the clinic. The exosomes exhibit a diversified repertoire of functional non-coding RNAs (ncRNAs) and have the potential to transfer these biologically active transcripts to the recipient cells, where they are found to modulate a diverse array of functions. Altered expression of the ncRNAs in the exosomes has been linked with the regenerative potential and development of various diseases, including cardiac, neurological, skeletal, and cancer. Also, modulating the expression of ncRNAs in these exosomes has been found to improve their therapeutic impact. Moreover, many of these ncRNAs are expressed explicitly in the MSC-derived exosomes, making them ideal candidates for regenerative medicine, including tissue engineering research. In this review, we detail the recent advances in regenerative medicine and summarize the evidence supporting the altered expression of the ncRNA repertoire specific to MSCs under different degenerative diseases. We also discuss the therapeutic role of these ncRNA for the prevention of these various degenerative diseases and their future in translational medicine.
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Affiliation(s)
- Tarun Pant
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Matea Juric
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Zeljko J. Bosnjak
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, United States
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States
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Marconi GD, Fonticoli L, Della Rocca Y, Rajan TS, Piattelli A, Trubiani O, Pizzicannella J, Diomede F. Human Periodontal Ligament Stem Cells Response to Titanium Implant Surface: Extracellular Matrix Deposition. BIOLOGY 2021; 10:931. [PMID: 34571808 PMCID: PMC8470763 DOI: 10.3390/biology10090931] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 12/24/2022]
Abstract
The major challenge for dentistry is to provide the patient an oral rehabilitation to maintain healthy bone conditions in order to reduce the time for loading protocols. Advancement in implant surface design is necessary to favour and promote the osseointegration process. The surface features of titanium dental implant can promote a relevant influence on the morphology and differentiation ability of mesenchymal stem cells, induction of the osteoblastic genes expression and the release of extracellular matrix (ECM) components. The present study aimed at evaluating the in vitro effects of two different dental implants with titanium surfaces, TEST and CTRL, to culture the human periodontal ligament stem cells (hPDLSCs). Expression of ECM components such as Vimentin, Fibronectin, N-cadherin, Laminin, Focal Adhesion Kinase (FAK) and Integrin beta-1 (ITGB1), and the osteogenic related markers, as runt related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), were investigated. Human PDLSCs cultured on the TEST implant surface demonstrated a better cell adhesion capability as observed by Scanning Electron Microscopy (SEM) and immunofluorescence analysis. Moreover, immunofluorescence and Western blot experiments showed an over expression of Fibronectin, Laminin, N-cadherin and RUNX2 in hPDLSCs seeded on TEST implant surface. The gene expression study by RT-PCR validated the results obtained in protein assays and exhibited the expression of RUNX2, ALP, Vimentin (VIM), Fibronectin (FN1), N-cadherin (CDH2), Laminin (LAMB1), FAK and ITGB1 in hPDLSCs seeded on TEST surface compared to the CTRL dental implant surface. Understanding the mechanisms of ECM components release and its regulation are essential for developing novel strategies in tissue engineering and regenerative medicine. Our results demonstrated that the impact of treated surfaces of titanium dental implants might increase and accelerate the ECM apposition and provide the starting point to initiate the osseointegration process.
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Affiliation(s)
- Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (G.D.M.); (A.P.)
| | - Luigia Fonticoli
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (L.F.); (Y.D.R.); (O.T.); (F.D.)
| | - Ylenia Della Rocca
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (L.F.); (Y.D.R.); (O.T.); (F.D.)
| | | | - Adriano Piattelli
- Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (G.D.M.); (A.P.)
| | - Oriana Trubiani
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (L.F.); (Y.D.R.); (O.T.); (F.D.)
| | | | - Francesca Diomede
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; (L.F.); (Y.D.R.); (O.T.); (F.D.)
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Prządka P, Buczak K, Frejlich E, Gąsior L, Suliga K, Kiełbowicz Z. The Role of Mesenchymal Stem Cells (MSCs) in Veterinary Medicine and Their Use in Musculoskeletal Disorders. Biomolecules 2021; 11:1141. [PMID: 34439807 PMCID: PMC8391453 DOI: 10.3390/biom11081141] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/27/2021] [Accepted: 07/30/2021] [Indexed: 12/11/2022] Open
Abstract
Regenerative medicine is a dynamically developing field of human and veterinary medicine. The animal model was most commonly used for mesenchymal stem cells (MSCs) treatment in experimental and preclinical studies with a satisfactory therapeutic effect. Year by year, the need for alternative treatments in veterinary medicine is increasing, and other applications for promising MSCs and their biological derivatives are constantly being sought. There is also an increase in demand for other methods of treating disease states, of which the classical treatment methods did not bring the desired results. Cell therapy can be a realistic option for treating human and animal diseases in the near future and therefore additional research is needed to optimize cell origins, numbers, or application methods in order to standardize the treatment process and assess its effects. The aim of the following work was to summarize available knowledge about stem cells in veterinary medicine and their possible application in the treatment of chosen musculoskeletal disorders in dogs and horses.
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Affiliation(s)
- Przemysław Prządka
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Krzysztof Buczak
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
| | - Ewelina Frejlich
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Ludwika Gąsior
- Vets & Pets Veterinary Clinic, Zakladowa 11N, 50-231 Wroclaw, Poland;
| | - Kamil Suliga
- Student Veterinary Surgical Society “LANCET”, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwaldzki 51, 50-366 Wroclaw, Poland;
| | - Zdzisław Kiełbowicz
- Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Science, Pl. Grunwadzki 51, 50-366 Wroclaw, Poland; (K.B.); (Z.K.)
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Khoury MA, Chamari K, Tabben M, Alkhelaifi K, Ricardo T, Damián C, D'hooghe P. Expanded adipose derived mesenchymal stromal cells are effective in treating chronic insertional patellar tendinopathy: clinical and MRI evaluations of a pilot study. J Exp Orthop 2021; 8:49. [PMID: 34213678 PMCID: PMC8253873 DOI: 10.1186/s40634-021-00358-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/02/2021] [Indexed: 01/09/2023] Open
Abstract
Purpose Effect of ultrasound guided injections of autologous ASCs in chronic recalcitrant patellar tendinopathy. Methods Fourteen patients (16 knees, 12/2 males/females) with chronic, recalcitrant (unsuccessfully treated with nonoperative treatments) insertional PT underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. Stromal vascular fraction cells (SVF) were expanded by in-vitro culture and characterized by flow cytometry. Players were injected with three bi-weekly injections of ASCs followed by physiotherapy. They underwent serial clinical evaluations during a 12-month period with repeated MRI at 6-month post-injection. Results Victorian Institute of sports assessment-patellar tendon questionnaire (VISA-P) scores improved from 43.8 ± 4.9 at baseline to 58.1 ± 7.1, 70.3 ± 7.9 and 78.7 ± 7.5 at 3, 6, and12months follow-up, respectively. (p = 0.0004 comparing each variable with the previous one). Mean Visual analogue pain in sports (VAS-sport) score during practice significantly decreased from 7.4 ± 0.5 at baseline to 5.2 ± 1.5 9 (p = 0.0005), 3.3 ± 1.1 (p = 0.0004) and 1.5 ± 0.7 (P = 0.0004) at 3, 6, and 12 months, respectively. Mean Tegner-scores for patients were 8.0 ± 0.8 before injury and 2.3 ± 0.9 before treatment, thereafter, improving to 4.8 ± 0.8 and 7.2 ± 0.7 at 6- and 12- months, respectively (p = 0.0001). MRI assessed tendon width’ did not change over the first 6 months post-intervention. Significant changes were observed for: tendon thickness (12.8 ± 1.1 to 10.9 ± 0.7, P = 0.0001); tear length (9.3 ± 1.3 to 2.3 ± 0.7, P = 0.0001), tear width (6.3 ± 0.8 to 3.4 ± 0.4, P = 0.0001), and tear thickness (4.6 ± 0.4 to 2.6 ± 0., P = 0.0001) at baseline and 6 months, respectively. Conclusion Patients with recalcitrant insertional PT showed significant clinical improvement and structural repair at the patellar insertional tendinopathy after injections of autologous ASCs. Results of this study are promising and open a new biological therapeutic modality to treat PT.
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Affiliation(s)
| | - Karim Chamari
- Aspetar Qatar Orthopaedic and Sports Medicine Hospital, P.O. Box 29222, Doha, Qatar
| | - Montassar Tabben
- Aspetar Qatar Orthopaedic and Sports Medicine Hospital, P.O. Box 29222, Doha, Qatar.
| | - Khalid Alkhelaifi
- Aspetar Qatar Orthopaedic and Sports Medicine Hospital, P.O. Box 29222, Doha, Qatar
| | | | - Couto Damián
- Himan Centro de Diagnóstico por Imágenes, Buenos Aires, Argentina
| | - Pieter D'hooghe
- Aspetar Qatar Orthopaedic and Sports Medicine Hospital, P.O. Box 29222, Doha, Qatar
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Equine Mesenchymal Stem/Stromal Cells Freeze-Dried Secretome (Lyosecretome) for the Treatment of Musculoskeletal Diseases: Production Process Validation and Batch Release Test for Clinical Use. Pharmaceuticals (Basel) 2021; 14:ph14060553. [PMID: 34200627 PMCID: PMC8226765 DOI: 10.3390/ph14060553] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/31/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023] Open
Abstract
In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility for veterinary clinical-use medicinal production. Critical parameters for quality control and batch release have been identified regarding (i) physicochemical properties; (ii) extracellular vesicle morphology, size distribution, and surface biomarker; (iii) protein and lipid content; (iv) requirements for injectable pharmaceutical dosage forms such as sterility, bacterial endotoxin, and Mycoplasma; and (v) in vitro potency tests, as anti-elastase activity and proliferative activity on musculoskeletal cell lines (tenocytes and chondrocytes) and mesenchymal stromal cells. Finally, proteins putatively responsible for the biological effects have been identified by Lyosecretome proteomic investigation: IL10RA, MXRA5, RARRES2, and ANXA1 modulate the inflammatory process RARRES2, NOD1, SERPINE1, and SERPINB9 with antibacterial activity. The work provides a proof-of-concept for the manufacturing of clinical-grade equine freeze-dried secretome, and prototypes are now available for safety and efficacy clinical trials in the treatment of equine musculoskeletal diseases
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Olaru M, Sachelarie L, Calin G. Hard Dental Tissues Regeneration-Approaches and Challenges. MATERIALS 2021; 14:ma14102558. [PMID: 34069265 PMCID: PMC8156070 DOI: 10.3390/ma14102558] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/10/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022]
Abstract
With the development of the modern concept of tissue engineering approach and the discovery of the potential of stem cells in dentistry, the regeneration of hard dental tissues has become a reality and a priority of modern dentistry. The present review reports the recent advances on stem-cell based regeneration strategies for hard dental tissues and analyze the feasibility of stem cells and of growth factors in scaffolds-based or scaffold-free approaches in inducing the regeneration of either the whole tooth or only of its component structures.
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Affiliation(s)
- Mihaela Olaru
- “Petru Poni” Institute of Macromolecular Chemistry, 41 A Grigore Ghica Voda Alley, 700487 Iasi, Romania;
| | - Liliana Sachelarie
- Faculty of Medical Dentistry, “Apollonia” University of Iasi, 2 Muzicii Str., 700399 Iasi, Romania;
- Correspondence:
| | - Gabriela Calin
- Faculty of Medical Dentistry, “Apollonia” University of Iasi, 2 Muzicii Str., 700399 Iasi, Romania;
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Garcia-Contreras M, Thakor AS. Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. Cell Death Discov 2021; 7:98. [PMID: 33972507 PMCID: PMC8110535 DOI: 10.1038/s41420-021-00471-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/05/2021] [Accepted: 04/07/2021] [Indexed: 12/16/2022] Open
Abstract
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), are driven by neuroinflammation triggered by activated microglial cells; hence, the phenotypic regulation of these cells is an appealing target for intervention. Human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) may be a potential therapeutic candidate to treat NDs given their immunomodulatory properties. Evidence suggests that the mechanism of action of hAD-MSCs is through their secretome, which includes secreted factors such as cytokines, chemokines, or growth factors as well as extracellular vesicles (EVs). Recently, EVs have emerged as important mediators in cell communication given, they can transfer proteins, lipids, and RNA species (i.e., miRNA, mRNA, and tRNAs) to modulate recipient cells. However, the therapeutic potential of hAD-MSCs and their secreted EVs has not been fully elucidated with respect to human microglia. In this study, we determined the therapeutic potential of different hAD-MSCs doses (200,000, 100,000, and 50,000 cells) or their secreted EVs (50, 20, or 10 µg/ml), on human microglial cells (HMC3) that were activated by lipopolysaccharides (LPS). Upregulation of inducible nitric oxide synthase (iNOS), an activation marker of HMC3 cells, was prevented when they were cocultured with hAD-MSCs and EVs. Moreover, hAD-MSCs inhibited the secretion of proinflammatory factors, such as IL-6, IL-8, and MCP-1, while their secreted EVs promoted the expression of anti-inflammatory mediators such as IL-10 or TIMP-1 in activated microglia. The present data therefore support a role for hAD-MSCs and their secreted EVs, as potential therapeutic candidates for the treatment of NDs.
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Affiliation(s)
- Marta Garcia-Contreras
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA, 94304, USA
| | - Avnesh S Thakor
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA, 94304, USA.
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Motohara T, Yoshida GJ, Katabuchi H. The hallmarks of ovarian cancer stem cells and niches: Exploring their harmonious interplay in therapy resistance. Semin Cancer Biol 2021; 77:182-193. [PMID: 33812986 DOI: 10.1016/j.semcancer.2021.03.038] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 03/20/2021] [Accepted: 03/29/2021] [Indexed: 12/18/2022]
Abstract
The concept of a "cancer stem cell" has evolved over the past decades, and research on cancer stem cell biology has entered into a stage of remarkable progress. Cancer stem cells are a major determining factor contributing to the establishment of phenotypic and functional intratumoral heterogeneity in synchronization with their surrounding "cancer stem cell niches." They serve as the driving force for cancer initiation, metastasis, and therapeutic resistance in various types of malignancies. In verity, reciprocal interplay between ovarian cancer stem cells and their niches involves a complex but ingeniously orchestrated tumor microenvironment within the intraperitoneal milieu and especially contribute to chemotherapy resistance in patients with advanced ovarian cancer. Herein, we review the principles of our current understanding of the biological features of ovarian cancer stem cells, focusing mainly on the precise mechanisms underlying acquired chemotherapy resistance. Furthermore, we highlight the specific roles of various cancer-associated stromal and immune cells in creating possible cancer stem cell niches that regulate ovarian cancer stemness.
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Affiliation(s)
- Takeshi Motohara
- Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto City, Kumamoto, 860-8556, Japan.
| | - Go J Yoshida
- Department of Immunological Diagnosis, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hidetaka Katabuchi
- Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto City, Kumamoto, 860-8556, Japan
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Latest advances to enhance the therapeutic potential of mesenchymal stromal cells for the treatment of immune-mediated diseases. Drug Deliv Transl Res 2021; 11:498-514. [PMID: 33634433 DOI: 10.1007/s13346-021-00934-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2021] [Indexed: 02/06/2023]
Abstract
Mesenchymal stromal cells (MSCs) present the capacity to secrete multiple immunomodulatory factors in response to their microenvironment. This property grants them a golden status among the novel alternatives to treat multiple diseases in which there is an unneeded or exaggerated immune response. However, important challenges still make difficult the clinical implementation of MSC-based therapies, being one of the most remarkable the lack of efficacy due to their transient immunomodulatory effects. To overcome this issue and boost the regulatory potential of MSCs, multiple strategies are currently being explored. Some of them consist of ex vivo pre-conditioning MSCs prior to their administration, including exposure to pro-inflammatory cytokines or to low oxygen concentrations. However, currently, alternative strategies that do not require such ex vivo manipulation are gaining special attention. Among them, the recreation of a three dimensional (3D) environment is remarkable. This approach has been reported to not only boost the immunomodulatory potential of MSCs but also increase their in vivo persistence and viability. The present work revises the therapeutic potential of MSCs, highlighting their immunomodulatory activity as a potential treatment for diseases caused by an exacerbated or unnecessary immune response. Moreover, it offers an updated vision of the most widely employed pre-conditioning strategies and 3D systems intended to enhance MSC-mediated immunomodulation, to conclude discussing the major challenges still to overcome in the field.
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Liu M, Ding H, Wang H, Wang M, Wu X, Gan L, Cheng L, Li X. Moringa oleifera leaf extracts protect BMSC osteogenic induction following peroxidative damage by activating the PI3K/Akt/Foxo1 pathway. J Orthop Surg Res 2021; 16:150. [PMID: 33610167 PMCID: PMC7896384 DOI: 10.1186/s13018-021-02284-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 02/08/2021] [Indexed: 12/28/2022] Open
Abstract
Objective We aimed to investigate the therapeutic effects of Moringa oleifera leaf extracts on osteogenic induction of rat bone marrow mesenchymal stem cells (BMSCs) following peroxidative damage and to explore the underlying mechanisms. Methods Conditioned medium was used to induce osteogenic differentiation of BMSCs, which were treated with H2O2, Moringa oleifera leaf extracts-containing serum, or the phosphatidyl inositol-3 kinase (PI3K) inhibitor wortmannin, alone or in combination. Cell viability was measured using the MTT assay. Cell cycle was assayed using flow cytometry. Expression levels of Akt, phosphorylated (p)Akt, Foxo1, and cleaved caspase-3 were analyzed using western blot analysis. The mRNA levels of osteogenesis-associated genes, including alkaline phosphatase (ALP), collagen І, osteopontin (OPN), and Runx2, were detected using qRT-PCR. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and ALP activity were detected using commercially available kits. Osteogenic differentiation capability was determined using alizarin red staining. Results During osteogenic induction of rat BMSCs, H2O2 reduced cell viability and proliferation, inhibited osteogenesis, increased ROS and MDA levels, and decreased SOD and GSH-PX activity. H2O2 significantly reduced pAkt and Foxo1 expression, and increased cleaved caspase-3 levels in BMSCs. Additional treatments with Moringa oleifera leaf extracts partially reversed the H2O2-induced changes. Wortmannin partially attenuated the effects of Moringa oleifera leaf extracts on protein expression of Foxo1, pAkt, and cleaved caspase-3, as well as mRNA levels of osteogenesis-associated genes. Conclusion Moringa oleifera leaf extracts ameliorate peroxidative damage and enhance osteogenic induction of rat BMSCs by activating the PI3K/Akt/Foxo1 pathway.
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Affiliation(s)
- Meiling Liu
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Haifeng Ding
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Hongzhi Wang
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Manfeng Wang
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Xiaowei Wu
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
| | - Lu Gan
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China.
| | - Luyang Cheng
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
| | - Xianglu Li
- Department of Geriatrics, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150086, China
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Elashry MI, Baulig N, Wagner AS, Klymiuk MC, Kruppke B, Hanke T, Wenisch S, Arnhold S. Combined macromolecule biomaterials together with fluid shear stress promote the osteogenic differentiation capacity of equine adipose-derived mesenchymal stem cells. Stem Cell Res Ther 2021; 12:116. [PMID: 33579348 PMCID: PMC7879632 DOI: 10.1186/s13287-021-02146-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 01/06/2021] [Indexed: 11/10/2022] Open
Abstract
Background Combination of mesenchymal stem cells (MSCs) and biomaterials is a rapidly growing approach in regenerative medicine particularly for chronic degenerative disorders including osteoarthritis and osteoporosis. The present study examined the effect of biomaterial scaffolds on equine adipose-derived MSC morphology, viability, adherence, migration, and osteogenic differentiation. Methods MSCs were cultivated in conjunction with collagen CultiSpher-S Microcarrier (MC), nanocomposite xerogels B30 and combined B30 with strontium (B30Str) biomaterials in osteogenic differentiation medium either under static or mechanical fluid shear stress (FSS) culture conditions. The data were generated by histological means, live cell imaging, cell viability, adherence and migration assays, semi-quantification of alkaline phosphatase (ALP) activity, and quantification of the osteogenic markers runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) expression. Results The data revealed that combined mechanical FSS with MC but not B30 enhanced MSC viability and promoted their migration. Combined osteogenic medium with MC, B30, and B30Str increased ALP activity compared to cultivation in basal medium. Osteogenic induction with MC, B30, and B30Str resulted in diffused matrix mineralization. The combined osteogenic induction with biomaterials under mechanical FSS increased Runx2 protein expression either in comparison to those cells cultivated in BM or those cells induced under static culture. Runx2 and ALP expression was upregulated following combined osteogenic differentiation together with B30 and B30Str regardless of static or FSS culture. Conclusions Taken together, the data revealed that FSS in conjunction with biomaterials promoted osteogenic differentiation of MSCs. This combination may be considered as a marked improvement for clinical applications to cure bone defects. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02146-7.
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Affiliation(s)
- Mohamed I Elashry
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, Frankfurter Str. 98, 35392, Giessen, Germany.
| | - Nadine Baulig
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, Frankfurter Str. 98, 35392, Giessen, Germany
| | - Alena-Svenja Wagner
- Clinic of Small Animals, c/o Institute of Veterinary Anatomy, Histology and Embryology, Justus Liebig University of Giessen, 35392, Giessen, Germany.,Institute of Veterinary Physiology and Biochemistry, Justus Liebig University of Giessen, 35392, Giessen, Germany
| | - Michele C Klymiuk
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, Frankfurter Str. 98, 35392, Giessen, Germany
| | - Benjamin Kruppke
- Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden, Budapester Str. 27, 01069, Dresden, Germany
| | - Thomas Hanke
- Institute of Materials Science, Max Bergmann Center of Biomaterials, Technische Universität Dresden, Budapester Str. 27, 01069, Dresden, Germany
| | - Sabine Wenisch
- Clinic of Small Animals, c/o Institute of Veterinary Anatomy, Histology and Embryology, Justus Liebig University of Giessen, 35392, Giessen, Germany
| | - Stefan Arnhold
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, Frankfurter Str. 98, 35392, Giessen, Germany
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Podestà MA, Remuzzi G, Casiraghi F. Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation. Front Immunol 2021; 11:618243. [PMID: 33643298 PMCID: PMC7902912 DOI: 10.3389/fimmu.2020.618243] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/29/2020] [Indexed: 12/29/2022] Open
Abstract
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
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Affiliation(s)
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy
| | - Federica Casiraghi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Bergamo, Italy
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Wu Z, Zhu M, Mou XX, Ye L. Overexpressing of caveolin-1 in mesenchymal stem cells promotes deep second-degree burn wound healing. J Biosci Bioeng 2021; 131:341-347. [PMID: 33423964 DOI: 10.1016/j.jbiosc.2020.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/22/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022]
Abstract
Burn injury is one of the most common physical injuries in clinic. It is a big challenge to find an ideal treatment for burn injury. Mesenchymal stem cells (MSCs) have been suggested as a promising candidate for wound healing. However, it is critical to improve the therapeutic efficiency of MSCs for treatment of burn injury. Here, we demonstrated that overexpression of caveolin-1, the main component of the caveolae plasma membranes, promoted the proliferation of MSCs both in vitro and in vivo. Moreover, transplantation of MSCs overexpressing caveolin-1 facilitated the expression of various growth factors and immunoregulatory cytokines and accelerated deep second-degree burn wound healing in a rat model of burn injury. Our results suggest that overexpression of caveolin-1 can improve the therapeutic efficiency of MSCs, which may be a promising strategy for the treatment of deep second-degree burn injury in clinic.
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Affiliation(s)
- Zhongmin Wu
- Department of Anatomy, Medical College of Taizhou University, Taizhou 317000, China; Department of Burn, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, China
| | - Min Zhu
- Department of Burn, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, China
| | - Xiao-Xin Mou
- Department of Burn, First People's Hospital of Taizhou City, Taizhou 318020, China
| | - Liyue Ye
- Department of Burn, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai 317000, China.
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Xiong YY, Gong ZT, Tang RJ, Yang YJ. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction. Am J Cancer Res 2021; 11:1046-1058. [PMID: 33391520 PMCID: PMC7738892 DOI: 10.7150/thno.53326] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023] Open
Abstract
Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molecular and cellular basis are urgently needed. Exosomes are a type of extracellular vesicles which contain a large amount of biologically active substances, like lipids, nucleic acids, proteins and so on. Emerging evidence suggests key roles of exosomes in immune regulation post AMI. A variety of immune cells participate in the immunomodulation after AMI, working together to clean up necrotic tissue and repair damaged myocardium. Stem cell therapy for myocardial infarction has long been a research hotspot during the last two decades and exosomes secreted by stem cells are important active substances and have similar therapeutic effects of immunomodulation, anti-apoptosis, anti-fibrotic and angiogenesis to those of stem cells themselves. Therefore, in this review, we focus on the characteristics and roles of exosomes produced by both of endogenous immune cells and exogenous stem cells in myocardial repair through immunomodulation after AMI.
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Vohra M, Sharma A, Bagga R, Arora SK. Human umbilical cord-derived mesenchymal stem cells induce tissue repair and regeneration in collagen-induced arthritis in rats. J Clin Transl Res 2020; 6:203-216. [PMID: 33564725 PMCID: PMC7868118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/14/2020] [Accepted: 10/14/2020] [Indexed: 10/31/2022] Open
Abstract
The immunosuppressive and anti-inflammatory properties of mesenchymal stem/stromal cells (MSCs) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis (RA). MSCs derived from bone marrow and adipose tissue has earlier been tried with limited success. However, Wharton's jelly present in human umbilical cord is discarded after delivery which makes a rich source of MSCs with least ethical issues. The immunomodulatory properties of human umbilical cord-derived MSCs (UC-MSCs) were evaluated in-vitro on the mononuclear cells from synovial fluid (SF) and peripheral blood of RA patients. The therapeutic potential of UC-MSCs was checked by transplanting the cells in rats with collagen-induced arthritis (CIA). MSCs isolated from Wharton's Jelly significantly suppressed the proliferation and activation of lymphocytes from both peripheral blood as well as SF of RA patients, down-modulated the functions of activated CD4+, CD8+ T-cells, suppressed the secretion of pro-inflammatory cytokines, and induced the expansion of T-regulatory cells. Xenotransplantation of UC-MSCs in CIA rats clearly indicated a sustained impact in terms of slowing down the progression of disease activity and reversal of arthritic processes along with triggering of joint tissue repair mechanisms, which could be observed till 6 weeks post-transplantation. The results from the current study suggest that human umbilical cord is a rich source of MSCs for allotransplantation. The UC-MSCs may be used successfully as a cell-based therapeutic option either in isolation or in conjunction with existing therapeutic drugs not only to relieve the joint inflammation but also regenerate the damaged bone and cartilage tissues in arthritis. RELEVANCE TO PATIENTS The current study highlights the potential use of MSCs as a cell-based therapeutic option for the treatment of inflammatory RA.
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Affiliation(s)
- Mehak Vohra
- 1Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Aman Sharma
- 2Department of Internal Medicine (Rheumatology), Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rashmi Bagga
- 3Department of Obstetrics and Gynaecology Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil K. Arora
- 1Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India,,
Corresponding author: Sunil K. Arora Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012, India
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Dehdashtian A, Bratley JV, Svientek SR, Kung TA, Awan TM, Cederna PS, Kemp SW. Autologous fat grafting for nerve regeneration and neuropathic pain: current state from bench-to-bedside. Regen Med 2020; 15:2209-2228. [PMID: 33264053 DOI: 10.2217/rme-2020-0103] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Despite recent advances in microsurgical techniques, functional recovery following peripheral nerve injury remains slow and inadequate. Poor peripheral nerve regeneration not only leaves patients with significant impairments, but also commonly leads to the development of debilitating neuropathic pain. Recent research has demonstrated the potential therapeutic benefits of adipose-derived stem cells, to enhance nerve regeneration. However, clinical translation remains limited due to the current regulatory burdens of the US FDA. A reliable and immediately translatable alternative is autologous fat grafting, where native adipose-derived stem cells present in the transferred tissue can potentially act upon regenerating axons. This review presents the scope of adipose tissue-based therapies to enhance outcomes following peripheral nerve injury, specifically focusing on their role in regeneration and ameliorating neuropathic pain.
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Affiliation(s)
- Amir Dehdashtian
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA
| | - Jarred V Bratley
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA
| | - Shelby R Svientek
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA
| | - Theodore A Kung
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA
| | - Tariq M Awan
- Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI 48109, USA
| | - Paul S Cederna
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
| | - Stephen Wp Kemp
- Department of Surgery, Section of Plastic & Reconstructive Surgery, University of Michigan, Ann Arbor, MI 48109, USA.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
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An Emerging Target in the Battle against Osteoarthritis: Macrophage Polarization. Int J Mol Sci 2020; 21:ijms21228513. [PMID: 33198196 PMCID: PMC7697192 DOI: 10.3390/ijms21228513] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 12/14/2022] Open
Abstract
Osteoarthritis (OA) is one of the most prevalent chronic joint diseases worldwide, which causes a series of problems, such as joint pain, muscle atrophy, and joint deformities. Benefiting from some advances in the clinical treatment of OA, the quality of life of OA patients has been improved. However, the clinical need for more effective treatments for OA is still very urgent. Increasing findings show that macrophages are a critical breakthrough in OA therapy. Stimulated by different factors, macrophages are differentiated into two phenotypes: the pro-inflammatory M1 type and anti-inflammatory M2 type. In this study, various therapeutic reagents for macrophage-dependent OA treatment are summarized, including physical stimuli, chemical compounds, and biological molecules. Subsequently, the mechanisms of action of various approaches to modulating macrophages are discussed, and the signaling pathways underlying these treatments are interpreted. The NF-κB signaling pathway plays a vital role in the occurrence and development of macrophage-mediated OA, as NF-κB signaling pathway agonists promote the occurrence of OA, whereas NF-κB inhibitors ameliorate OA. Besides, several signaling pathways are also involved in the process of OA, including the JNK, Akt, MAPK, STAT6, Wnt/β-catenin, and mTOR pathways. In summary, macrophage polarization is a critical node in regulating the inflammatory response of OA. Reagents targeting the polarization of macrophages can effectively inhibit inflammation in the joints, which finally relieves OA symptoms. Our work lays the foundation for the development of macrophage-targeted therapeutic molecules and helps to elucidate the role of macrophages in OA.
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