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Kharat A, Bhate K, Sanap A, Kheur S, Contractor M, Suryawanshi P, Bhonde R. Exploring the Differentiation Abilities of Hair Follicle and Dental Pulp Stem Cells Into Islet Like Cells. Cell Biol Int 2025; 49:634-644. [PMID: 40014298 DOI: 10.1002/cbin.70010] [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: 06/30/2024] [Revised: 01/03/2025] [Accepted: 02/16/2025] [Indexed: 02/28/2025]
Abstract
This study aimed to compare the differentiation potential of dental pulp-derived mesenchymal stem cells (DP-MSCs) and hair follicle-derived mesenchymal stem cells (HF-MSCs), which originated from the ectoderm. Dental pulps were separated from the extracted wisdom teeth during dental surgery, and Hair follicles were extracted from the scalp of patients undergoing hair transplantation. We cultivated the cell in cell culture media, supplemented with additional nutrients. After the fourth passage, the homogeneous population of DP-MSCs and HF-MSCs was analyzed for the surface markers (CD73, CD90, and CD105) by fluorescence-activated cell sorting. In vitro, the multi-lineage differentiation potential for both the MSCs was tested with respective induction media such as osteogenic, chondrogenic, adipogenic, and insulin-producing cells. Following the fourth passage, identical fibroblast-like cells were noted in each culture plate. Mesenchymal stem cell marker was expressed in both DP-MSCs and HF-MSCs. Both the DP-MSCs and HF-MSCs exhibited similar differentiation potential toward osteogenic, chondrogenic, and adipogenic differentiation. However, there was a difference in the differentiation potential into IPCs. HF-MSCs showed higher C-peptide and insulin secretion response to glucose, PDX1, and Insulin gene expression compared to DP-MSCs. These findings suggest that although DP-MSCs and HF-MSCs showed similar stemness properties, they differ in their differentiation potential towards insulin-producing cells (IPCs). This is the first report showing the potential of HF-MSCs to generate IPCs, revealing hair follicles as a novel and promising source for autologous stem cell therapy in diabetes. The generated islet organoids can be used for diabetic drug toxicity testing and screening.
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Affiliation(s)
- Avinash Kharat
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Kalyani Bhate
- Department of Oral and Maxillofacial Surgery, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Avinash Sanap
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Supriya Kheur
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Murtuza Contractor
- Department of Oral and Maxillofacial Surgery, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Poonam Suryawanshi
- The Central Research Facility, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Ramesh Bhonde
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
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Feng X, Zhang H, Yang S, Cui D, Wu Y, Qi X, Su Z. From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes. Mol Cell Biochem 2025; 480:173-190. [PMID: 38642274 DOI: 10.1007/s11010-024-04999-x] [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: 01/16/2024] [Accepted: 03/21/2024] [Indexed: 04/22/2024]
Abstract
Loss and functional failure of pancreatic β-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for β-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional β-cells. In this review, we first introduce the development of functional β-cells and their heterogeneity and then turn to highlight recent advances in the generation of β-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.
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Affiliation(s)
- Xingrong Feng
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Hongmei Zhang
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Shanshan Yang
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Daxin Cui
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Yanting Wu
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Xiaocun Qi
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China
| | - Zhiguang Su
- Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China.
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Zeinhom A, Fadallah SA, Mahmoud M. Human mesenchymal stem/stromal cell based-therapy in diabetes mellitus: experimental and clinical perspectives. Stem Cell Res Ther 2024; 15:384. [PMID: 39468609 PMCID: PMC11520428 DOI: 10.1186/s13287-024-03974-z] [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: 09/02/2024] [Accepted: 10/04/2024] [Indexed: 10/30/2024] Open
Abstract
Diabetes mellitus (DM), a chronic metabolic disease, poses a significant global health challenge, with current treatments often fail to prevent the long-term disease complications. Mesenchymal stem/stromal cells (MSCs) are, adult progenitors, able to repair injured tissues, exhibiting regenerative effects and immunoregulatory and anti-inflammatory responses, so they have been emerged as a promising therapeutic approach in many immune-related and inflammatory diseases. This review summarizes the therapeutic mechanisms and outcomes of MSCs, derived from different human tissue sources (hMSCs), in the context of DM type 1 and type 2. Animal model studies and clinical trials indicate that hMSCs can facilitate pleiotropic actions in the diabetic milieu for improved metabolic indices. In addition to modulating abnormally active immune system, hMSCs can ameliorate peripheral insulin resistance, halt beta-cell destruction, preserve residual beta-cell mass, promote beta-cell regeneration and insulin production, support islet grafts, and correct lipid metabolism. Moreover, hMSC-free derivatives, importantly extracellular vesicles, have shown potent experimental anti-diabetic efficacy. Moreover, the review discusses the diverse priming strategies that are introduced to enhance the preclinical anti-diabetic actions of hMSCs. Such strategies are recommended to restore the characteristics and functions of MSCs isolated from patients with DM for autologous implications. Finally, limitations and merits for the wide spread clinical applications of MSCs in DM such as the challenge of autologous versus allogeneic MSCs, the optimal MSC tissue source and administration route, the necessity of larger clinical trials for longer evaluation duration to assess safety concerns, are briefly presented.
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Affiliation(s)
- Alaa Zeinhom
- Biotechnology Department, Faculty of Science, Cairo University, Cairo Governorate, 12316, Egypt
| | - Sahar A Fadallah
- Biotechnology Department, Faculty of Science, Cairo University, Cairo Governorate, 12316, Egypt
| | - Marwa Mahmoud
- Human Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, 12622, Egypt.
- Stem Cell Research Unit, Medical Research Centre of Excellence, NRC, Cairo, Egypt.
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Abstract
In order to improve bioavailability, stability, control release, and target delivery of active pharmaceutical ingredients (APIs), as well as to mask their bitter taste, to increase their efficacy, and to minimize their side effects, a variety of microencapsulation (including nanoencapsulation, particle size <100 nm) technologies have been widely used in the pharmaceutical industry. Commonly used microencapsulation technologies are emulsion, coacervation, extrusion, spray drying, freeze-drying, molecular inclusion, microbubbles and microsponge, fluidized bed coating, supercritical fluid encapsulation, electro spinning/spray, and polymerization. In this review, APIs are categorized by their molecular complexity: small APIs (compounds with low molecular weight, like Aspirin, Ibuprofen, and Cannabidiol), medium APIs (compounds with medium molecular weight like insulin, peptides, and nucleic acids), and living microorganisms (such as probiotics, bacteria, and bacteriophages). This article provides an overview of these microencapsulation technologies including their processes, matrix, and their recent applications in microencapsulation of APIs. Furthermore, the advantages and disadvantages of these common microencapsulation technologies in terms of improving the efficacy of APIs for pharmaceutical treatments are comprehensively analyzed. The objective is to summarize the most recent progresses on microencapsulation of APIs for enhancing their bioavailability, control release, target delivery, masking their bitter taste and stability, and thus increasing their efficacy and minimizing their side effects. At the end, future perspectives on microencapsulation for pharmaceutical applications are highlighted.
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Affiliation(s)
- Cuie Yan
- Division of Encapsulation, Blue California, Rancho Santa Margarita, California 92688, United States
| | - Sang-Ryoung Kim
- Division of Encapsulation, Blue California, Rancho Santa Margarita, California 92688, United States
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Fareez IM, Liew FF, Widera D, Mayeen NF, Mawya J, Abu Kasim NH, Haque N. Application of Platelet-Rich Plasma as a Stem Cell Treatment - an Attempt to Clarify a Common Public Misconception. Curr Mol Med 2024; 24:689-701. [PMID: 37171013 DOI: 10.2174/1566524023666230511152646] [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: 01/10/2023] [Revised: 03/29/2023] [Accepted: 04/03/2023] [Indexed: 05/13/2023]
Abstract
In recent years, there has been a significant increase in the practice of regenerative medicine by health practitioners and direct-to-consumer businesses globally. Among different tools of regenerative medicine, platelet-rich plasma (PRP) and stem cell-based therapies have received considerable attention. The use of PRP, in particular, has gained popularity due to its easy access, simple processing techniques, and regenerative potential. However, it is important to address a common misconception amongst the general public equating to PRP and stem cells due to the demonstrated efficacy of PRP in treating musculoskeletal and dermatological disorders. Notably, PRP promotes regeneration by providing growth factors or other paracrine factors only. Therefore, it cannot replenish or replace the lost cells in conditions where a large number of cells are required to regenerate tissues and/or organs. In such cases, cellbased therapies are the preferred option. Additionally, other tools of regenerative medicine, such as bioprinting, organoids, and mechanobiology also rely on stem cells for their success. Hence, healthcare and commercial entities offering direct-to-customer regenerative therapies should not mislead the public by claiming that the application of PRP is a stem cell-based therapy. Furthermore, it is important for regulatory bodies to strictly monitor these profit-driven entities to prevent them from providing unregulated regenerative treatments and services that claim a broad variety of benefits with little proof of efficacy, safety concerns, and obscure scientific justification.
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Affiliation(s)
- Ismail M Fareez
- School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, 40450, Selangor, Malaysia
| | - Fong Fong Liew
- Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Selangor, 42610, Malaysia
| | - Darius Widera
- Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Reading, UK
| | - Naiyareen Fareeza Mayeen
- Faculty of Biology, Ludwig-Maximilians-University of Munich, Planegg- Martinsried, 82152, Germany
- TotiCell Limited, Dhaka, 1209, Bangladesh
| | | | - Noor Hayaty Abu Kasim
- Faculty of Dentistry, University of Malaya, Kuala Lumpur, 50603, Malaysia
- Faculty of Dentistry, University Kebangsaan Malaysia, Kuala Lumpur, 50300, Malaysia
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Kasturi M, Mathur V, Gadre M, Srinivasan V, Vasanthan KS. Three Dimensional Bioprinting for Hepatic Tissue Engineering: From In Vitro Models to Clinical Applications. Tissue Eng Regen Med 2024; 21:21-52. [PMID: 37882981 PMCID: PMC10764711 DOI: 10.1007/s13770-023-00576-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/07/2023] [Accepted: 07/11/2023] [Indexed: 10/27/2023] Open
Abstract
Fabrication of functional organs is the holy grail of tissue engineering and the possibilities of repairing a partial or complete liver to treat chronic liver disorders are discussed in this review. Liver is the largest gland in the human body and plays a responsible role in majority of metabolic function and processes. Chronic liver disease is one of the leading causes of death globally and the current treatment strategy of organ transplantation holds its own demerits. Hence there is a need to develop an in vitro liver model that mimics the native microenvironment. The developed model should be a reliable to understand the pathogenesis, screen drugs and assist to repair and replace the damaged liver. The three-dimensional bioprinting is a promising technology that recreates in vivo alike in vitro model for transplantation, which is the goal of tissue engineers. The technology has great potential due to its precise control and its ability to homogeneously distribute cells on all layers in a complex structure. This review gives an overview of liver tissue engineering with a special focus on 3D bioprinting and bioinks for liver disease modelling and drug screening.
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Affiliation(s)
- Meghana Kasturi
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vidhi Mathur
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Mrunmayi Gadre
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Varadharajan Srinivasan
- Department of Civil Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Kirthanashri S Vasanthan
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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Placental mesenchymal stem cells restore glucose and energy homeostasis in obesogenic adipocytes. Cell Tissue Res 2023; 391:127-144. [PMID: 36227376 DOI: 10.1007/s00441-022-03693-y] [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: 12/08/2021] [Accepted: 09/14/2022] [Indexed: 01/18/2023]
Abstract
Obesity (Ob) depicts a state of energy imbalance(s) being characterized by the accumulation of excessive fat and which predisposes to several metabolic diseases. Mesenchymal stem cells (MSCs) represent a promising option for addressing obesity and its associated metabolic co-morbidities. The present study aims at assessing the beneficial effects of human placental MSCs (P-MSCs) in mitigating Ob-associated insulin resistance (IR) and mitochondrial dysfunction both in vivo and in vitro. Under obesogenic milieu, adipocytes showed a significant reduction in glucose uptake, and impaired insulin signaling with decreased expression of UCP1 and PGC1α, suggestive of dysregulated non-shivering thermogenesis vis-a-vis mitochondrial biogenesis respectively. Furthermore, obesogenic adipocytes demonstrated impaired mitochondrial respiration and energy homeostasis evidenced by reduced oxygen consumption rate (OCR) and blunted ATP/NAD+/NADP+ production respectively. Interestingly, co-culturing adipocytes with P-MSCs activated PI3K-Akt signaling, improved glucose uptake, diminished ROS production, enhanced mitochondrial OCR, improved ATP/NAD+/NADP+ production, and promoted beiging of adipocytes evidenced by upregulated expression of PRDM16, UCP1, and PGC1α expression. In vivo, P-MSCs administration increased the peripheral blood glucose uptake and clearance, and improved insulin sensitivity and lipid profile with a coordinated increase in the ratio of ATP/ADP and NAD+ and NADP+ in the white adipose tissue (WAT), exemplified in WNIN/GR-Ob obese mutant rats. In line with in vitro findings, there was a significant reduction in adipocyte hypertrophy, increased mitochondrial staining, and thermogenesis. Our findings advocate for a therapeutic application of P-MSCs for improving glucose and energy homeostasis, i.e., probably restoring non-shivering thermogenesis towards obesity management.
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Kharat A, Sanap A, Kheur S, Shekatkar M, Bhonde R. Insulin-producing cell clusters derived from human gingival mesenchymal stem cells as a model for diabetes research. Mol Biol Rep 2022; 49:11973-11982. [PMID: 36271309 DOI: 10.1007/s11033-022-08008-6] [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: 06/20/2022] [Accepted: 10/04/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND The human gingiva-derived mesenchymal stem cells (hGMSCs) possess a great potential to develop the cell-based therapy for diabetes due to its unscarred healing capacity and reparative potential. In this current study, we isolated, cultured and characterised the GMSCs and explored their potential to differentiate into Insulin Producing Cell Clusters (IPCCs). METHODS The cells derived from gingival tissues exhibited fibroblast-like morphology. The flow cytometric analysis revealed positive expression of CD73(97.43%), CD90(95.05%), and CD105(93.17%) and negative expression of CD34(0.05%), CD45(0.09%), and HLA-DR (0.025) surface markers. We then converted this adherent fibroblast-like GMSCs into floating IPCCs using a sequential three-step protocol containing a different combination of differentiating agents. Initially, the presence of insulin in IPCCs was confirmed by dithizone staining. Glucose-stimulated insulin secretion (GSIS) assay confirmed that IPCCs secrete insulin in response to glucose. RESULTS Generated IPCCs express pancreatic markers such as insulin, pdx1, glucagon, GLUT4 and GLUT2 as evidenced by RT-PCR analysis. Our results unequivocally showed that IPCCs can be generated from gingiva which is a potential source of postnatal MSCs. Our results offer the IPCCs generated from hGMSCs a platform for screening anti-diabetic drugs and a new autologous source of tissue for islet transplantation for the treatment of diabetes. CONCLUSIONS Our results unequivocally demonstrate for the first time that hGMSCs can be used as an attractive non-invasive tissue source for generating IPCCs, which can be employed in diabetes research for screening antidiabetic agents and also for transplantation in type 1 diabetic patients as autologous source without the need of immunosuppression.
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Affiliation(s)
- Avinash Kharat
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Avinash Sanap
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Supriya Kheur
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Madhura Shekatkar
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India
| | - Ramesh Bhonde
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, India.
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Shamsuddin SA, Chan AML, Ng MH, Yazid MD, Law JX, Hj Idrus RB, Fauzi MB, Mohd Yunus MH, Lokanathan Y. Stem cells as a potential therapy in managing various disorders of metabolic syndrome: a systematic review. Am J Transl Res 2021; 13:12217-12227. [PMID: 34956448 PMCID: PMC8661211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 10/12/2021] [Indexed: 06/14/2023]
Abstract
Recent explorations on mesenchymal stem/stromal cells (MSC) have reported a promising future for cell-based therapies. MSCs are widely sourced from various tissues and express unique properties of regenerative potential and immunomodulation. Currently, there is a growing interest in utilizing MSC for treatment of chronic diseases to overcome the drawbacks of chemical drugs. Metabolic Syndrome (MetS) is described as a cluster of metabolic abnormalities categorized as abdominal obesity, dyslipidaemia, hypertension, hypertriglyceridemia, and hyperglycaemia. Patients diagnosed with MetS have a high predisposition for developing cardiovascular complications, diabetes, non-alcoholic fatty liver diseases, bone loss, cancer, and mortality. Hence, research on MSC as therapy for MetS and related diseases, is greatly valued and are advantaged by the low immunogenicity with high regenerative capacity. However, there are many obstacles to be addressed such as the safety, efficacy, and consistency of different MSC sources. Additionally, factors such as effective dose level and delivery method are equally important to achieve uniform therapeutic outcomes. This systematic review discusses the potential roles of MSC in managing the multiple clusters of MetS. Research articles during the past 20 years were systematically searched and filtered to update the progress in the field of MSC therapy in managing various components of MetS. The different sources of MSC, dosage, method of delivery and outcome measures for the stem cell therapies were compiled from the systematically selected research articles. It can be concluded from the review of the selected articles that MSCs can improve the various disorders of MetS such as abdominal obesity, hyperglycaemia, hypertriglyceridemia and hypertension, and represent a promising alternative to conventional therapy of the MetS cluster.
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Affiliation(s)
- Sharen Aini Shamsuddin
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Alvin Man Lung Chan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Min Hwei Ng
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Muhammad Dain Yazid
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Jia Xian Law
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Ruszymah Binti Hj Idrus
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Mh Busra Fauzi
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Mohd Heikal Mohd Yunus
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
| | - Yogeswaran Lokanathan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan MalaysiaCheras 56000, Kuala Lumpur, Malaysia
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Zhang S, Wang Q, Ji H, Lu H, Yang Q, Yin J, Guan W. Porcine pancreas mesenchymal cell characterization and functional differentiation into insulin‑producing cells in vitro. Mol Med Rep 2021; 24:737. [PMID: 34414446 PMCID: PMC8404098 DOI: 10.3892/mmr.2021.12377] [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: 06/23/2020] [Accepted: 01/05/2021] [Indexed: 12/13/2022] Open
Abstract
Cell therapy is a promising treatment strategy for patients with type 1 diabetes. Porcine pancreas-derived mesenchymal stromal cells (PMSCs) have emerged as one of the most widely used cell resources owing to their high proliferative capacity and multi-lineage differentiation potential. Although the induction efficiency and insulin production of induced insulin-producing cells (IPCs) derived from PMSCs have been estimated, these have primarily focused on the function of induced cells and alterations in related gene expression levels. However, morphological analyses and biological characterization of PMSCs and induced IPCs have not been conducted. Therefore, the present study aimed to optimize an induction protocol, resulting in a 78.92% induction rate. The present study investigated the biological characteristics of PMSCs and optimized a simple but functional three-step protocol to transform PMSCs into IPCs. PMSCs were isolated from 2–3-month-old Bama miniature pig embryos, which were then subcultured to passage 16. The surface markers pancreatic and duodenal homeobox 1, NK6 homeobox 1, Vimentin, Nestin, CD73, CD90, neurogenin 3, CD45 and CD34 were detected by immunofluorescence staining or flow cytometry. Proliferative capacity was evaluated by constructing growth curves of cells at three different passages. Functional differentiation was assessed by morphological observation, dithizone staining, and immunofluorescence staining of C-peptide, insulin, NK6 homeobox 1 and glucagon. The production of insulin by differentiated cells was also analyzed by performing ELISAs. The results demonstrated that differentiated cells were distributed with an islet-like structure, expressed specific markers C-peptide and insulin, and displayed glucose responsiveness. The results of the present study demonstrated that PMSCs were functionally induced into IPCs with the optimized three-step protocol, which may serve as a potential cell therapy strategy to widen the availability and promote the clinical application of cell therapy.
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Affiliation(s)
- Shang Zhang
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Qi Wang
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Hongbing Ji
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Huidi Lu
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Qin Yang
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Jiahui Yin
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
| | - Weijun Guan
- Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China
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Kotikalapudi N, Sampath SJP, Sukesh Narayan S, R B, Nemani H, Mungamuri SK, Venkatesan V. The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems. Sci Rep 2021; 11:16983. [PMID: 34417511 PMCID: PMC8379204 DOI: 10.1038/s41598-021-96121-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 08/04/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in pre-clinical/Ob-T2D management.
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Affiliation(s)
- Nagasuryaprasad Kotikalapudi
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Samuel Joshua Pragasam Sampath
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Sinha Sukesh Narayan
- Division of Food Safety, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Bhonde R
- Department of Regenerative Medicine, Manipal Institute of Regenerative Medicine, GKVK Post, Bellary Road, Allalasandra, Yelahanka, Bangalore, 560065, India
- Dr. D. Y. Patil Vidyapeeth, Pune, 411018, India
| | - Harishankar Nemani
- Division of Animal Facility, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Sathish Kumar Mungamuri
- Division of Food Safety, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Vijayalakshmi Venkatesan
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India.
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12
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Gorodetsky R, Aicher WK. Allogenic Use of Human Placenta-Derived Stromal Cells as a Highly Active Subtype of Mesenchymal Stromal Cells for Cell-Based Therapies. Int J Mol Sci 2021; 22:5302. [PMID: 34069909 PMCID: PMC8157571 DOI: 10.3390/ijms22105302] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/14/2021] [Accepted: 05/14/2021] [Indexed: 12/13/2022] Open
Abstract
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.
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Affiliation(s)
- Raphael Gorodetsky
- Biotechnology and Radiobiology Laboratory, Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
| | - Wilhelm K. Aicher
- Center of Medical Research, Department of Urology at UKT, Eberhard-Karls-University, 72076 Tuebingen, Germany
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Sampath SJP, Kotikalapudi N, Venkatesan V. A novel therapeutic combination of mesenchymal stem cells and stigmasterol to attenuate osteoarthritis in rodent model system-a proof of concept study. Stem Cell Investig 2021; 8:5. [PMID: 33829057 DOI: 10.21037/sci-2020-048] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 03/10/2021] [Indexed: 01/15/2023]
Abstract
Mesenchymal stem cells (MSCs) have gained wide therapeutic acceptance in regenerative medicine due to their potential in repair process in restoring the damaged tissues and controlling inflammation. In the present study, we report for the first time the beneficial effects of combining placental-derived MSCs (hPMSCs) with stigmasterol-a plant-derived sterol to accelerate cartilage repair and regeneration in a monosodium-iodoacetate (MIA) induced osteoarthritis (OA) rat model. Control animals (Group I) received no treatment. Experimental animals (Group II) received a single intra-articular injection of MIA (2 mg) in the right knee joints. The Group II animals developed OA-like lesions within a week of MIA injection. They were subdivided further as: (II-A): OA, (II-B): OA+hPMSCs (2×106 cells, single-dose/intra-articular injection), (II-C): OA+stigmasterol (20 µg/mL, single-dose/intra-articular injection) and (II-D): OA+hPMSCs+stigmasterol. The animals were monitored for four more weeks after which they were sacrificed, the right limbs dissected out and assessed for cartilage repair and regeneration using micro-computed tomography (micro-CT) and histology. Results showed that the combined administration of hPMSCs with stigmasterol (II-D) was the most effective in correcting the OA lesions, with concomitant repair and regeneration. However, hPMSCs (II-B) or stigmasterol (II-C) per se treated groups showed only marginal beneficial effects and were not significant. Thus the present study provides valuable insights in situ using a combination of hPMSCs and stigmasterol towards cartilage repair and regeneration. We advocate the participation of populating cells or residual chondrocytes in addition to its anti-inflammatory functions.
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Affiliation(s)
- Samuel Joshua Pragasam Sampath
- Stem Cell Research Laboratory, Department of Biochemistry/Cell and Molecular Biology, National Institute of Nutrition (Indian Council of Medical Research), Tarnaka, Hyderabad, Telangana, India
| | - Nagasuryaprasad Kotikalapudi
- Stem Cell Research Laboratory, Department of Biochemistry/Cell and Molecular Biology, National Institute of Nutrition (Indian Council of Medical Research), Tarnaka, Hyderabad, Telangana, India
| | - Vijayalakshmi Venkatesan
- Stem Cell Research Laboratory, Department of Biochemistry/Cell and Molecular Biology, National Institute of Nutrition (Indian Council of Medical Research), Tarnaka, Hyderabad, Telangana, India
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Kim KS, Choi YK, Kim MJ, Hwang JW, Min K, Jung SY, Kim SK, Choi YS, Cho YW. Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell. Diabetes Metab J 2021; 45:260-269. [PMID: 32662257 PMCID: PMC8024157 DOI: 10.4093/dmj.2019.0191] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 03/08/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. METHODS Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. RESULTS Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. CONCLUSION UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.
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Affiliation(s)
- Kyung-Soo Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Yeon Kyung Choi
- Department of Biotechnology, CHA University, Seongnam, Korea
| | - Mi Jin Kim
- Department of Biotechnology, CHA University, Seongnam, Korea
| | - Jung Wook Hwang
- Department of Biotechnology, CHA University, Seongnam, Korea
| | - Kyunghoon Min
- Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Sang Youn Jung
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Soo-Kyung Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Yong-Soo Choi
- Department of Biotechnology, CHA University, Seongnam, Korea
| | - Yong-Wook Cho
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
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15
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Peng SY, Wu TH, Lin TY, Hii LY, Chan KS, Fu TY, Chang SC, Shen PC, Liu KY, Shaw SW. Application of cattle placental stem cells for treating ovarian follicular cyst. World J Stem Cells 2020; 12:1366-1376. [PMID: 33312404 PMCID: PMC7705470 DOI: 10.4252/wjsc.v12.i11.1366] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 07/02/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND High humidity and temperature in Taiwan have significant effects on the reproductivity of Holstein cattle, resulting in the occurrence of bovine ovarian follicular cyst (OFC). Because of economic loss from OFC, manual rupture and hormone injection have been advocated for the management of OFC. However, these incomplete treatments increase hormone resistance in cattle. Mesenchymal stem cells (MSCs) derived from placental stem cells (PSCs) demonstrate potential properties for the treatment of several diseases via promoting angiogenesis and immune modulation. AIM To establish the possibility of cattle placental stem cells (CPSCs) as a treatment modality for OFC of cows in Taiwan. METHODS The cows with OFC were divided into three groups: control (BC1 and BC2), hormone (H1 and H2), and CPSC (PS1 and PS2) treatment groups. In the hormone treatment group, the cows were given gonadotrophin-releasing hormone (GnRH)-prostaglandin-GnRH intramuscular injection with or without drainage of follicular fluid. In the CPSC treatment group, CPSCs were isolated from the placenta after labor. With the identification of surface antigen on stem cells, the cows were administered ovarian injection of 1 × 106 or 6 × 106 CPSCs with drainage. In all groups, OFC was scanned by ultrasound once a week for a total of seven times. The concentrations of estradiol and progesterone in serum were tested in the same period. The estrus cycle was analyzed by food intake and activity. If estrus was detected, artificial insemination was conducted. Then the cow was monitored by ultrasound for confirmation of pregnancy. RESULTS After 7 d of culture, CPSCs were successfully isolated from placental pieces. CPSCs significantly proliferated every 24 h and had high expression of MSC markers such as cluster of differentiation 44, as determined by flow cytometry. Ultrasound showed lower numbers of OFCs with drainage of follicular fluid. We achieved recovery rates of 0%, 50%, 50%, 75%, 75% and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. Higher concentrations of progesterone were detected in the CPSC treatment groups. However, both hormone and CPSC treatment groups had no significant difference in the concentration of estradiol. The estrus rate was 0%, 100%, 25%, 75%, 75% and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. The two fetuses were born in H2 and PS1. In brief, cows with CPSC injection achieved higher recovery, estrus, and inseminated conception rates. CONCLUSION CPSCs have efficacy in treating cows with OFC, and thus, may serve as an alternative treatment for reproductive disorders.
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Affiliation(s)
- Shao-Yu Peng
- Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
| | - Tsung-Hsin Wu
- Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
| | - Tzu-Yi Lin
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ling-Yien Hii
- Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Kok-Seong Chan
- Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Tzu-Yen Fu
- Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
| | - Shen-Chang Chang
- Kaohsiung Animal Propagation Station, Livestock Research Institute, Council of Agriculture, Executive Yuan, Pingtung 912, Taiwan
| | - Perng-Chih Shen
- Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
| | - Kang-You Liu
- Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
| | - Steven W. Shaw
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan
- Prenatal Cell and Gene Therapy Group, Institute for Women's Health, University College London, London WC1E 6HU, United Kingdom.
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16
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Kuncorojakti S, Rodprasert W, Yodmuang S, Osathanon T, Pavasant P, Srisuwatanasagul S, Sawangmake C. Alginate/Pluronic F127-based encapsulation supports viability and functionality of human dental pulp stem cell-derived insulin-producing cells. J Biol Eng 2020; 14:23. [PMID: 32855655 PMCID: PMC7446208 DOI: 10.1186/s13036-020-00246-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 08/13/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Current approach for diabetes treatment remained several adverse events varied from gastrointestinal to life-threatening symptoms. Regenerative therapy regarding Edmonton protocol has been facing serious limitations involving protocol efficiency and safety. This led to the study for alternative insulin-producing cell (IPC) resource and transplantation platform. In this study, evaluation of encapsulated human dental pulp-derived stem cell (hDPSC)-derived IPCs by alginate (ALG) and pluronic F127-coated alginate (ALGPA) was performed. RESULTS The results showed that ALG and ALGPA preserved hDPSC viability and allowed glucose and insulin diffusion in and out. ALG and ALGPA-encapsulated hDPSC-derived IPCs maintained viability for at least 336 h and sustained pancreatic endoderm marker (NGN3), pancreatic islet markers (NKX6.1, MAF-A, ISL-1, GLUT-2 and INSULIN), and intracellular pro-insulin and insulin expressions for at least 14 days. Functional analysis revealed a glucose-responsive C-peptide secretion of ALG- and ALGPA-encapsulated hDPSC-derived IPCs at 14 days post-encapsulation. CONCLUSION ALG and ALGPA encapsulations efficiently preserved the viability and functionality of hDPSC-derived IPCs in vitro and could be the potential transplantation platform for further clinical application.
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Affiliation(s)
- Suryo Kuncorojakti
- International Graduate Course in Veterinary Science and Technology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Watchareewan Rodprasert
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Supansa Yodmuang
- Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330 Thailand
- Excellence Center for Advanced Therapy Medicinal Products, King Chulalongkorn Memorial Hospital, Bangkok, 10330 Thailand
| | - Thanaphum Osathanon
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330 Thailand
- Center of Excellence in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Prasit Pavasant
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330 Thailand
- Center of Excellence in Regenerative Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Sayamon Srisuwatanasagul
- Department of Veterinary Anatomy, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
| | - Chenphop Sawangmake
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
- Veterinary Clinical Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
- Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand
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17
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Mirdamadi ES, Kalhori D, Zakeri N, Azarpira N, Solati-Hashjin M. Liver Tissue Engineering as an Emerging Alternative for Liver Disease Treatment. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:145-163. [PMID: 31797731 DOI: 10.1089/ten.teb.2019.0233] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic liver diseases affect thousands of lives throughout the world every year. The shortage of liver donors for transplantation has been the main driving force to employ alternative methods such as liver tissue engineering (LTE) in fabricating a three-dimensional transplantable liver tissue or enhancing cell delivery techniques alleviating the need for liver donors. LTE consists of three components, cells, ECM (extracellular matrix), and signaling molecules, which we discuss the first and second. The three most common cell sources used in LTE are human and animal primary hepatocytes, and stem cells for different applications. Two major categories of ECM are used to mimic the microenvironment of these cells, named scaffolds and microbeads. Scaffolds have been made by numerous methods with a wide range of synthetic and natural biomaterials. Cell encapsulation has also been utilized by many polymeric biomaterials. To investigate their functions, many properties have been discussed in the literature, such as biochemical, geometrical, and mechanical properties, in both of these categories. Overall, LTE shows excellent potential in assisting hepatic disorders. However, some challenges exist that prevent the practical use of it clinically, making LTE an ongoing research subject in the scientific society.
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Affiliation(s)
- Elnaz Sadat Mirdamadi
- BioFabrication Lab (BFL), Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Dianoosh Kalhori
- BioFabrication Lab (BFL), Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Nima Zakeri
- BioFabrication Lab (BFL), Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehran Solati-Hashjin
- BioFabrication Lab (BFL), Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
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18
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Chen L, Forsyth NR, Wu P. Chorionic and amniotic placental membrane-derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities. J Tissue Eng Regen Med 2019; 14:243-256. [PMID: 31701635 DOI: 10.1002/term.2988] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 10/04/2019] [Accepted: 10/17/2019] [Indexed: 12/11/2022]
Abstract
Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.
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Affiliation(s)
- Liyun Chen
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.,Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | - Nicholas R Forsyth
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K
| | - Pensee Wu
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.,Academic Unit of Obstetrics and Gynaecology, University Hospital of North Midlands Stoke-on-Trent, U.K.,Keele Cardiovascular Research Group, Institute for Applied Clinical Sciences and Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University Stoke-on-Trent, U.K
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19
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Pavathuparambil Abdul Manaph N, Sivanathan KN, Nitschke J, Zhou XF, Coates PT, Drogemuller CJ. An overview on small molecule-induced differentiation of mesenchymal stem cells into beta cells for diabetic therapy. Stem Cell Res Ther 2019; 10:293. [PMID: 31547868 PMCID: PMC6757413 DOI: 10.1186/s13287-019-1396-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 07/23/2019] [Accepted: 08/26/2019] [Indexed: 12/17/2022] Open
Abstract
The field of regenerative medicine provides enormous opportunities for generating beta cells from different stem cell sources for cellular therapy. Even though insulin-secreting cells can be generated from a variety of stem cell types like pluripotent stem cells and embryonic stem cells, the ideal functional cells should be generated from patients' own cells and expanded to considerable levels by non-integrative culture techniques. In terms of the ease of isolation, plasticity, and clinical translation to generate autologous cells, mesenchymal stem cell stands superior. Furthermore, small molecules offer a great advantage in terms of generating functional beta cells from stem cells. Research suggests that most of the mesenchymal stem cell-based protocols to generate pancreatic beta cells have small molecules in their cocktail. However, most of the protocols generate cells that mimic the characteristics of human beta cells, thereby generating "beta cell-like cells" as opposed to mature beta cells. Diabetic therapy becomes feasible only when there are robust, functional, and safe cells for replacing the damaged or lost beta cells. In this review, we discuss the current protocols used to generate beta cells from mesenchymal cells, with emphasis on small molecule-mediated conversion into insulin-producing beta cell-like cells. Our data and the data presented from the references within this review would suggest that although mesenchymal stem cells are an attractive cell type for cell therapy they are not readily converted into functional mature beta cells.
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Affiliation(s)
- Nimshitha Pavathuparambil Abdul Manaph
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia. .,School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, South Australia, 5000, Australia. .,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia. .,Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
| | - Kisha N Sivanathan
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.,School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, South Australia, 5000, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia.,Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
| | - Jodie Nitschke
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia
| | - Xin-Fu Zhou
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia
| | - Patrick T Coates
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia
| | - Christopher John Drogemuller
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, 5000, Australia
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20
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Lim R. Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog? Stem Cells Transl Med 2019; 6:1767-1776. [PMID: 28834402 PMCID: PMC5689753 DOI: 10.1002/sctm.16-0447] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 06/16/2017] [Indexed: 12/11/2022] Open
Abstract
The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem-like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro-angiogenic and immunomodulatory properties of the stem and stem-like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose-derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem-like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767-1776.
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Affiliation(s)
- Rebecca Lim
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.,Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
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21
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Kumar SA, Delgado M, Mendez VE, Joddar B. Applications of stem cells and bioprinting for potential treatment of diabetes. World J Stem Cells 2019; 11:13-32. [PMID: 30705712 PMCID: PMC6354103 DOI: 10.4252/wjsc.v11.i1.13] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 12/26/2018] [Accepted: 01/05/2019] [Indexed: 02/06/2023] Open
Abstract
Currently, there does not exist a strategy that can reduce diabetes and scientists are working towards a cure and innovative approaches by employing stem cell-based therapies. On the other hand, bioprinting technology is a novel therapeutic approach that aims to replace the diseased or lost β-cells, insulin-secreting cells in the pancreas, which can potentially regenerate damaged organs such as the pancreas. Stem cells have the ability to differentiate into various cell lines including insulin-producing cells. However, there are still barriers that hamper the successful differentiation of stem cells into β-cells. In this review, we focus on the potential applications of stem cell research and bioprinting that may be targeted towards replacing the β-cells in the pancreas and may offer approaches towards treatment of diabetes. This review emphasizes on the applicability of employing both stem cells and other cells in 3D bioprinting to generate substitutes for diseased β-cells and recover lost pancreatic functions. The article then proceeds to discuss the overall research done in the field of stem cell-based bioprinting and provides future directions for improving the same for potential applications in diabetic research.
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Affiliation(s)
- Shweta Anil Kumar
- Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory, Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, United States
| | - Monica Delgado
- Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory, Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, United States
| | - Victor E Mendez
- Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory, Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, United States
| | - Binata Joddar
- Inspired Materials and Stem-Cell Based Tissue Engineering Laboratory, Department of Metallurgical, Materials and Biomedical Engineering, University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, United States
- Border Biomedical Research Center, University of Texas at El Paso, 500 W University Avenue, El Paso, TX 79968, United States.
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22
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Kim HJ, Li Q, Song WJ, Yang HM, Kim SY, Park SC, Ahn JO, Youn HY. Fibroblast growth factor-1 as a mediator of paracrine effects of canine adipose tissue-derived mesenchymal stem cells on in vitro-induced insulin resistance models. BMC Vet Res 2018; 14:351. [PMID: 30445954 PMCID: PMC6240186 DOI: 10.1186/s12917-018-1671-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Accepted: 10/25/2018] [Indexed: 12/13/2022] Open
Abstract
Background In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon. Results Gene expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4) were used as indicators of insulin resistance. Relative protein expression levels of IRS-1 and GLUT4 were augmented in the cAT-MSC CM treatment group compared to insulin resistance models, indicating beneficial effects of cAT-MSC to DM, probably by actions of secreting factors. With reference to previous studies on fibroblast growth factor-1 (FGF1), we proposed FGF1 as a key contributing factor to the mechanism of action. We added anti-FGF1 neutralizing antibody to the CM-treated insulin resistance models. As a result, significantly diminished protein levels of IRS-1 and GLUT4 were observed, supporting our assumption. Similar results were observed in glucose uptake assay. Conclusions Accordingly, this study advocated the potential of FGF-1 from cAT-MSC CM as an alternative insulin sensitizer and discovered a signalling factor associated with the paracrine effects of cAT-MSC. Electronic supplementary material The online version of this article (10.1186/s12917-018-1671-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hyeon-Jin Kim
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Qiang Li
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Woo-Jin Song
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Hye-Mi Yang
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Su-Yeon Kim
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Sang-Chul Park
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea
| | - Jin-Ok Ahn
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.,Current Address: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kangwon National University, Chuncheon, 24341, Gangwondo, Republic of Korea
| | - Hwa-Young Youn
- Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea.
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Kharat A, Chandravanshi B, Gadre S, Patil V, Bhonde R, Dubhashi A. IGF-1 and somatocrinin trigger islet differentiation in human amniotic membrane derived mesenchymal stem cells. Life Sci 2018; 216:287-294. [PMID: 30444986 DOI: 10.1016/j.lfs.2018.11.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 11/05/2018] [Accepted: 11/12/2018] [Indexed: 12/13/2022]
Abstract
AIM To induce differentiation of human amniotic membrane derived mesenchymal stem cells (hAMMSCs) into insulin producing cells (IPCs) by treating with somatocrinin or growth hormone releasing hormone (GHRH) and Insulin-like growth factor-1 (IGF-1). MAIN METHOD In this investigation, we cultivated and characterized hAMMSCs and then treated with IGF-1 and somatocrinin to find out whether this combination gives better yield of insulin producing cells. We showed that hAMMSCs can give rise to IPCs on exposure to serum-free defined media containing specific growth factors and differentiating agents in presence of IGF-1 and somatocrinin. KEY FINDING A combination of IGF-1 and somatocrinin lead to differentiation of large number of IPCs from hAMMSCs. These IPCs were found to be positive for dithizone indicating their insulin secretory mechanism. Moreover these cells were also found to be positive for C-peptide. IPCs released insulin in response to glucose challenge. Gene expression analysis exhibited significant up-regulation of pancreatic transcription factor GLUT2 and Insulin. SIGNIFICANCE Our data thus demonstrates for the first time that somatocrinin and IGF-1 synergistically enhance the differentiation of hAMMSCs into IPCs.
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Affiliation(s)
- Avinash Kharat
- Department of Bio-anylatical Sciences, Guru Nanak Khalsa College of Arts, Science & Commerce, Nathalal Parekh Marg, Matunga East, Mumbai 400019, Maharashtra, India; Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra 411018, India
| | - Bhawna Chandravanshi
- School of Regenerative Medicine, Manipal University, MAHE, GKVK Post, Bellary Road Allalasandra, Near Royal Orchid Yelahanka, Bangalore 560065, India
| | - Shashikant Gadre
- Department of Bio-anylatical Sciences, Guru Nanak Khalsa College of Arts, Science & Commerce, Nathalal Parekh Marg, Matunga East, Mumbai 400019, Maharashtra, India
| | - Vikrant Patil
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra 411018, India
| | - Ramesh Bhonde
- Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra 411018, India.
| | - Aparna Dubhashi
- Department of Bio-anylatical Sciences, Guru Nanak Khalsa College of Arts, Science & Commerce, Nathalal Parekh Marg, Matunga East, Mumbai 400019, Maharashtra, India.
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24
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The Effect of Chronic Inflammation and Oxidative and Endoplasmic Reticulum Stress in the Course of Metabolic Syndrome and Its Therapy. Stem Cells Int 2018; 2018:4274361. [PMID: 30425746 PMCID: PMC6217741 DOI: 10.1155/2018/4274361] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 09/26/2018] [Accepted: 10/03/2018] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MetS) is highly associated with a modern lifestyle. The prevalence of MetS has reached epidemic proportion and is still rising. The main cause of MetS and finally type 2 diabetes occurrence is excessive nutrient intake, lack of physical activity, and inflammatory cytokines secretion. These factors lead to redistribution of body fat and oxidative and endoplasmic reticulum (ER) stress occurrence, resulting in insulin resistance, increase adipocyte differentiation, and much elevated levels of proinflammatory cytokines. Cellular therapies, especially mesenchymal stem cell (MSC) transplantation, seem to be promising in the MetS and type 2 diabetes treatments, due to their immunomodulatory effect and multipotent capacity; adipose-derived stem cells (ASCs) play a crucial role in MSC-based cellular therapies. In this review, we focused on etiopathology of MetS, especially on the crosstalk between chronic inflammation, oxidative stress, and ER stress and their effect on MetS-related disease occurrence, as well as future perspectives of cellular therapies. We also provide an overview of therapeutic approaches that target endoplasmic reticulum and oxidative stress.
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25
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Current Status of Stem Cell Treatment for Type I Diabetes Mellitus. Tissue Eng Regen Med 2018; 15:699-709. [PMID: 30603589 DOI: 10.1007/s13770-018-0143-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/02/2018] [Accepted: 07/04/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans. METHODS Current treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into β islet cells. RESULTS These stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms. CONCLUSION Stem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.
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Yagi Mendoza H, Yokoyama T, Tanaka T, Ii H, Yaegaki K. Regeneration of insulin-producing islets from dental pulp stem cells using a 3D culture system. Regen Med 2018; 13:673-687. [PMID: 30028236 DOI: 10.2217/rme-2018-0074] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
AIM In this study, we aimed to establish the differentiation protocol of dental pulp stem cells (DPSCs) into pancreatic islets using a 3D structure. MATERIALS & METHODS DPSCs were differentiated in a 3D culture system using a stepwise protocol. Expression of β-cell markers, glucose-stimulated insulin secretion, and PI3K/AKT and WNT pathways were compared between monolayer-cultured pancreatic cells and islets. RESULTS Islet formation increased insulin and C-peptide production, and enhanced the expression of pancreatic markers. Glucose-dependent secretion of insulin was increased by islets. Pancreatic endocrine markers, transcriptional factors, and the PI3K/AKT and WNT pathways were also upregulated. CONCLUSION Pancreatic islets were generated from DPSCs in a 3D culture system. This system could provide novel strategies for controlling diabetes through regenerative medicine.
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Affiliation(s)
- Hiromi Yagi Mendoza
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Tomomi Yokoyama
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Tomoko Tanaka
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Hisataka Ii
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
| | - Ken Yaegaki
- Department of Oral Health, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi, Chiyoda ku, 102-8159 Tokyo, Japan
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27
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Abbaspanah B, Momeni M, Ebrahimi M, Mousavi SH. Advances in perinatal stem cells research: a precious cell source for clinical applications. Regen Med 2018; 13:595-610. [PMID: 30129876 DOI: 10.2217/rme-2018-0019] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 06/08/2018] [Indexed: 12/16/2022] Open
Abstract
Perinatal tissues possess numerous types of stem (stromal) cells, which are considered effective candidates for cell therapy. These tissues possess common characteristics of both embryonic and adult stem cells, and cell therapists have begun to use perinatal stem cells to treat several diseases. Despite their benefits, these cells are considered biological waste and usually discarded after delivery. This review highlights the characteristics and potential clinical applications in regenerative medicine of perinatal stem cell sources - cord blood hematopoietic stem cells, umbilical cord mesenchymal stem cells, amniotic membrane stem cells, amniotic fluid stem cells, amniotic epithelial cells and chorionic mesenchymal stem cells.
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Affiliation(s)
| | - Maryam Momeni
- Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
| | - Marzieh Ebrahimi
- Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
- Department of Stem Cells & Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
| | - Seyed Hadi Mousavi
- Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
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28
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Cho JS, Lee J, Jeong DU, Kim HW, Chang WS, Moon J, Chang JW. Effect of Placenta-Derived Mesenchymal Stem Cells in a Dementia Rat Model via Microglial Mediation: a Comparison between Stem Cell Transplant Methods. Yonsei Med J 2018; 59:406-415. [PMID: 29611403 PMCID: PMC5889993 DOI: 10.3349/ymj.2018.59.3.406] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 01/12/2018] [Accepted: 01/12/2018] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.
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Affiliation(s)
- Jae Sung Cho
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jihyeon Lee
- Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Da Un Jeong
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
| | - Han Wool Kim
- General Research Institute, Gangnam CHA General Hospital, Seoul, Korea
| | - Won Seok Chang
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jisook Moon
- General Research Institute, Gangnam CHA General Hospital, Seoul, Korea
- Department of Bioengineering, College of Life Science, CHA University, Seoul, Korea
| | - Jin Woo Chang
- Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
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29
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Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects. Stem Cells Int 2018. [PMID: 29535770 PMCID: PMC5822788 DOI: 10.1155/2018/4837930] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine.
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30
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Luo Y, Xu Y, Wang ZY, Li X, Xing WB, Zhang TC. The Synergy of Two Factors on Insulin Expression. Cell Reprogram 2018; 20:49-54. [PMID: 29303357 DOI: 10.1089/cell.2017.0026] [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: 11/13/2022] Open
Abstract
As a potential cure for diabetes, more and more attentions have been paid to organ transplants to replace insulin therapy. As a result, many researchers have explored out many programs to get insulin-producing cells (IPCs) to replace the defective β cells. Currently, more and more new induction methods are being proposed, and at the same time, more and more possible induction molecular mechanisms are being revealed. The purpose of this study was to explore whether and how the two factors pdx-1 and myocardin affected the differentiation of rat mesenchymal stem cells (rMSCs) into IPCs. In this study, we investigated the process of transfecting myocardin and/or pdx-1 in rMSCs in vitro. The results showed that rMSCs were able to secrete insulin after cotransfected with myocardin and pdx-1. At the same time, we explored the possible mechanism that myocardin and pdx-1 coinduced rMSCs into IPCs by forming a complex to promote the transcriptional activity of insulin. Our results may provide a theoretical basis to the study of islet transplantation in the future.
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Affiliation(s)
- Ying Luo
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China
| | - Yao Xu
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China
| | - Zhen-Yu Wang
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China
| | - Xi Li
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China
| | - Wei-Bing Xing
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China
| | - Tong-Cun Zhang
- 1 Institute of Biology and Medicine, Wuhan University of Science and Technology , Wuhan, China .,2 Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology , Tianjin, China
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31
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Pursani V, Kapoor S, Metkari SM, Nair P, Bhartiya D. Evaluating KIND1 human embryonic stem cell-derived pancreatic progenitors to ameliorate streptozotocin-induced diabetes in mice. Indian J Med Res 2017; 146:244-254. [PMID: 29265026 PMCID: PMC5761035 DOI: 10.4103/ijmr.ijmr_210_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background & objectives: Diabetes is a global disease burden. Various stem cell types are being explored to serve as an alternative source of islets. This study was conducted to evaluate the ability of in-house developed human embryonic stem (hES) cells-derived pancreatic progenitors to ameliorate diabetic symptoms in mice. Methods: Pancreatic progenitors were packed in macro-capsules and transplanted into six male Swiss mice and four mice were taken as controls. Thirty days post-transplantation, diabetes was induced by streptozotocin treatment. Mice were then followed up for >100 days and body weight and blood glucose levels were regularly monitored. Results: Control mice lost weight, maintained high glucose levels and did not survive beyond 40 days, whereas transplanted group maintained body weight and four of the six mice had lowered blood glucose levels. About five-fold increase was observed in human C-peptide levels in the recipients of progenitor transplants as compared to diabetic control. Interpretation & conclusions: The beneficial effect of transplanted cells was not long-lasting. Further studies are required to critically evaluate and compare the potential of endogenous pluripotent stem cells and hES cells-derived progenitors before moving from bench to the bedside.
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Affiliation(s)
- Varsha Pursani
- Department of Stem Cell Biology, ICMR-National Institute for Research in Reproductive Health, Mumbai, India
| | - Sona Kapoor
- Department of Stem Cell Biology, ICMR-National Institute for Research in Reproductive Health, Mumbai, India
| | - S M Metkari
- Department of Experimental Animal Facility, ICMR-National Institute for Research in Reproductive Health, Mumbai, India
| | - Prabha Nair
- Division of Tissue Engineering and Regeneration Technologies, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Deepa Bhartiya
- Department of Stem Cell Biology, ICMR-National Institute for Research in Reproductive Health, Mumbai, India
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32
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Lin W, Hsuan YCY, Su YC, Lin CH, Lin MT, Chen ZH, Chang CP, Lin KC. CD34 - human placenta-derived mesenchymal stem cells protect against heat stroke mortality in rats. Oncotarget 2017; 9:1992-2001. [PMID: 29416747 PMCID: PMC5788615 DOI: 10.18632/oncotarget.23324] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/09/2017] [Indexed: 01/01/2023] Open
Abstract
CD34 is a transmembrane phosphoglycoprotein used to selectively enrich bone marrow in hematopoietic stem cells for transplantation. Treating rats with CD34+ cells derived from human umbilical cord blood before or after heat stroke has been shown to promote survival. We investigated whether CD34– human placenta-derived stem cells (PDMSCs) could improve survival following heat stroke in rats. Rats were subjected to heat stress (42°C for 98 min) to induce heat stroke. Intravenous administration of PDMSCs 1 day before or immediately after the onset of heat stroke improved survival by 60% and 20%, respectively. Pre-treatment with CD34− PDMSCs protected against heat stroke injury more effectively than that treatment after injury. PDMSCs treatment attenuated cerebrovascular dysfunction, the inflammatory response, and lipid peroxidation. These data suggest human PDMSCs protect against heat stroke injury in rats. Moreover, these effects do not require the presence of CD34+ cells.
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Affiliation(s)
- Willie Lin
- Meridigen Biotech Co., Ltd., Taipei, Taiwan
| | | | - Yu-Chin Su
- Meridigen Biotech Co., Ltd., Taipei, Taiwan
| | | | - Mao-Tsun Lin
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Zi-Hao Chen
- Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Ching-Ping Chang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.,Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, Taiwan
| | - Kao-Chang Lin
- Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan
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Sanap A, Chandravanshi B, Shah T, Tillu G, Dhanushkodi A, Bhonde R, Joshi K. Herbal pre-conditioning induces proliferation and delays senescence in Wharton's Jelly Mesenchymal Stem Cells. Biomed Pharmacother 2017; 93:772-778. [PMID: 28724259 DOI: 10.1016/j.biopha.2017.06.107] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 06/15/2017] [Accepted: 06/29/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Mesenchymal Stem Cells (MSCs) are multipotent stem cells which are being explored for various clinical applications. Isolation and in-vitro expansion of MSCs remain important in achieving desired cell number for the therapy. However, in-vitro proliferation of MSCs is often associated with senescence and early onset of apoptosis which limits its therapeutic ability and long term clinical use. Tinospora cordifolia and Withania somnifera are used widely in Ayurveda: the traditional Indian system of medicine and are reported to have rejuvenating and anti-aging potential. In the present study, we investigated the effect of Tinospora cordifolia and Withania somnifera on proliferation and senescence of wharton's jelly MSCs (WJMSCs) in-vitro. METHODS WJMSCs were treated in culture medium with Tinospora cordifolia leaf and Withania somnifera root extracts to examine their effect on proliferation and senescence properties of WJMSCs. Proliferation of WJMSCs was assayed by cell count, MTT, BrdU incorporation assay, cell cycle analysis and Ki67 mRNA expression. Senescence was demonstrated using β-galactosidase senescence assay and associated mRNA markers. RESULTS Culture medium supplemented with Tinospora cordifolia leaf and Withania somnifera root extracts exhibited significant increase in proliferation of WJMSCs as evidenced by cell count and MTT assay. Cell cycle analysis using propidium iodide showed increase in G2/M phase and decrease in apoptotic cells. BrdU incorporation and upregulation of proliferation marker ki67 by RT PCR showed increased DNA synthesis/proliferation in Tinospora cordifolia and Withania somnifera extract treated MSCs. Delayed senescence was confirmed by β-galactosidase senescence assay and down regulation of senescence marker p21. CONCLUSION Our results demonstrate for the first time that Tinospora cordifolia and Withania somnifera extracts support proliferation and inhibit senescence in WJMSCs making them suitable candidates as supplements for in-vitro expansion without affecting the cell viability indicating its non-toxic nature.
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Affiliation(s)
- Avinash Sanap
- Department of Biotechnology, Sinhgad College of Engineering, Affiliated to Savitribai Phule Pune University, Pune 411041, India
| | | | - Tejas Shah
- Department of Biotechnology, Sinhgad College of Engineering, Affiliated to Savitribai Phule Pune University, Pune 411041, India
| | - Girish Tillu
- Interdisciplinary School of Health Sciences, Savitribai Phule Pune University, Pune 411007, India
| | - Anand Dhanushkodi
- School of Regenerative Medicine, Manipal University, Bangalore 560065, India
| | - Ramesh Bhonde
- School of Regenerative Medicine, Manipal University, Bangalore 560065, India
| | - Kalpana Joshi
- Department of Biotechnology, Sinhgad College of Engineering, Affiliated to Savitribai Phule Pune University, Pune 411041, India.
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34
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Balaji S, Zhou Y, Opara EC, Soker S. Combinations of Activin A or Nicotinamide with the Pancreatic Transcription Factor PDX1 Support Differentiation of Human Amnion Epithelial Cells Toward a Pancreatic Lineage. Cell Reprogram 2017. [PMID: 28632450 DOI: 10.1089/cell.2016.0043] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The differentiation of multipotent stem cells toward a pancreatic lineage provides us with an alternative cell-based therapeutic approach to type 1 diabetes and enables us to study pancreas development. The current study aims to study the effect of growth factors such as activin A or nicotinamide, alone and in combinations with the transcription factor, PDX1 (pancreatic and duodenal homeobox-1), on human amnion epithelial cells (hAECs) toward a pancreatic lineage. Ectopic expression of Pdx1 followed by treatment of hAECs with nicotinamide for 4 days resulted in strong induction of pancreatic endoderm and pancreatic progenitor genes, including NKX6.1 and NEUROD1. Pancreatic lineage cells expressing PDX1, SOX17, and RFX6 are derived from Pdx1-transduced hAECs treated with activin A or nicotinamide, but not cells treated with activin A or nicotinamide alone. Our study provides a novel culture protocol for generating pancreas-committed cells from hAECs and reveals an interplay between Pdx1 and activin A/nicotinamide signaling in early pancreatic fate determination.
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Affiliation(s)
- Shruti Balaji
- 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina.,2 Department of Biological Sciences, Birla Institute of Technology and Science , Goa, India
| | - Yu Zhou
- 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina
| | - Emmanuel C Opara
- 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina.,3 Virginia Tech-Wake Forest University School of Biomedical Engineering & Sciences , Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Shay Soker
- 1 Wake Forest Institute for Regenerative Medicine , Winston-Salem, North Carolina.,3 Virginia Tech-Wake Forest University School of Biomedical Engineering & Sciences , Wake Forest School of Medicine, Winston-Salem, North Carolina
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Mathew SA, Chandravanshi B, Bhonde R. Hypoxia primed placental mesenchymal stem cells for wound healing. Life Sci 2017. [PMID: 28625360 DOI: 10.1016/j.lfs.2017.06.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
AIMS To investigate how Placental Mesenchymal Stem Cells (P-MSCs) would adapt themselves and survive under hypoxic conditions which are prevalent in most injury sites. MAIN METHODS P-MSCs were isolated from term placenta and characterised under normoxia and hypoxia (2-2.5% O2). Cells were examined for morphology and surface marker variations by flow cytometry analysis. Glucose stimulated insulin secretion was assayed by Insulin ELISA Kit. Gene expression levels were estimated using Real Time PCR for hypoxia inducible factor1 alpha, Insulin (INS), Glucose transporters (GLUT-1, GLUT-2 and GLUT-3), Adhesion Proteins- Integrins, Fibronectin1 (FN1), E-Cadherin (CDH1), and N-Cadherin (CDH2) and angiogenesis marker VEGFA. Immunofluorescence assay was done to confirm the presence of C-Peptide, GLUT 2, E-Cadherin and ITGB3. Adhesion was confirmed assessed on fibronectin binding. KEY FINDINGS We show that insulin secretion is not hampered under hypoxia. We found an upregulation of glucose transporters under hypoxia indicating enhanced glucose uptake needed to cater to metabolic demands of proliferating cells. Up regulation of adhesion molecules was seen under hypoxia indicative of a favoured environment for retention of cells at the injury site. We also found increased level of angiogenesis of P-MSCs under hypoxia. SIGNIFICANCE Our present study thus demonstrates for the first time that P-MSCs modulate themselves under hypoxic conditions by secreting insulin, up regulating glucose transporters and adhesion molecules and eventually exhibiting an increased angiogenic potential. We thus infer that priming P-MSCs under hypoxia, could make them more suitable for wound healing applications.
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Affiliation(s)
- Suja Ann Mathew
- School of Regenerative Medicine, Manipal University, MAHE, GKVK Post, Bellary Road, Allalasandra, Near Royal Orchid, Yelahanka, Bangalore 560 065, India
| | - Bhawna Chandravanshi
- School of Regenerative Medicine, Manipal University, MAHE, GKVK Post, Bellary Road, Allalasandra, Near Royal Orchid, Yelahanka, Bangalore 560 065, India
| | - Ramesh Bhonde
- Dr D Y Patil University, Sant Tukaram Nagar, Maharashtra, Pune 411018, India.
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Pancreatic Islet Transplantation Technologies: State of the Art of Micro- and Macro-Encapsulation. CURRENT TRANSPLANTATION REPORTS 2017. [DOI: 10.1007/s40472-017-0154-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Potential clinical applications of placental stem cells for use in fetal therapy of birth defects. Placenta 2017; 59:107-112. [PMID: 28651900 DOI: 10.1016/j.placenta.2017.05.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 04/22/2017] [Accepted: 05/16/2017] [Indexed: 12/12/2022]
Abstract
Placental stem cells are of growing interest for a variety of clinical applications due to their multipotency and ready availability from otherwise frequently discarded biomaterial. Stem cells derived from the placenta have been investigated in a number of disease processes, including wound healing, ischemic heart disease, autoimmune disorders, and chronic lung or liver injury. Fetal intervention for structural congenital defects, such as spina bifida, has rapidly progressed as a field due to advances in maternal-fetal medicine and improving surgical techniques. In utero treatment of structural, as well as non-structural, congenital disorders with cell-based therapies is of particular interest given the immunologic immaturity and immunotolerant environment of the developing fetus. A comprehensive literature review was performed to assess the potential utilization of placenta-derived stem cells for in utero treatment of congenital disorders. Most studies are still in the preclinical phase, utilizing animal models of common congenital disorders. Future research endeavors may include autologous transplantation, gene transfers, induced pluripotent stem cells, or cell-free therapies derived from the stem cell secretome. Though much work still needs to be done, placental stem cells are a promising therapeutic agent for fetal intervention for congenital disease.
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Zang L, Hao H, Liu J, Li Y, Han W, Mu Y. Mesenchymal stem cell therapy in type 2 diabetes mellitus. Diabetol Metab Syndr 2017; 9:36. [PMID: 28515792 PMCID: PMC5433043 DOI: 10.1186/s13098-017-0233-1] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 05/05/2017] [Indexed: 02/06/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), which is characterized by the combination of relative insulin deficiency and insulin resistance, cannot be reversed with existing therapeutic strategies. Transplantation of insulin-producing cells (IPCs) was once thought to be the most promising strategy for treating diabetes, but the pace from the laboratory to clinical application has been obstructed due to its drawbacks. Mesenchymal stem cells (MSCs) harbor differentiation potential, immunosuppressive properties, and anti-inflammatory effects, and they are considered an ideal candidate cell type for treatment of DM. MSC-related research has demonstrated exciting therapeutic effects in glycemic control both in vivo and in vitro, and these results now have been translated into clinical practice. However, some critical potential problems have emerged from current clinical trials. Multi-center, large-scale, double-blind, and placebo-controlled studies with strict supervision are required before MSC transplantation can become a routine therapeutic approach for T2DM. We briefly review the molecular mechanism of MSC treatment for T2DM as well as the merits and drawbacks identified in current clinical trials.
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Affiliation(s)
- Li Zang
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853 China
| | - Haojie Hao
- Department of Molecular Biology, Institute of Basic Medicine, College of Life Science, Chinese PLA General Hospital, Beijing, 100853 China
| | - Jiejie Liu
- Department of Molecular Biology, Institute of Basic Medicine, College of Life Science, Chinese PLA General Hospital, Beijing, 100853 China
| | - Yijun Li
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853 China
| | - Weidong Han
- Department of Molecular Biology, Institute of Basic Medicine, College of Life Science, Chinese PLA General Hospital, Beijing, 100853 China
| | - Yiming Mu
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853 China
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Al Madhoun A, Ali H, AlKandari S, Atizado VL, Akhter N, Al-Mulla F, Atari M. Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton's jelly mesenchymal stem cells. Stem Cell Res Ther 2016; 7:165. [PMID: 27852316 PMCID: PMC5111269 DOI: 10.1186/s13287-016-0426-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Accepted: 10/18/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are gaining increasing interest as an alternative source of stem cells for regenerative medicine applications. Definitive endoderm (DE) specification is a prerequisite for the development of vital organs such as liver and pancreas. Hence, efficient induction of the DE lineage from stem cells is crucial for subsequent generation of clinically relevant cell types. Here we present a defined 3D differentiation protocol of WJ-MSCs into DE cells. METHODS WJ-MSCs were cultured in suspension to generate spheroids, about 1500 cells each, for 7 days. The serum-free differentiation media contained specific growth factors, cytokines, and small molecules that specifically regulate signaling pathways including sonic hedgehog, bone morphogenetic protein, Activin/Wnt, and Notch. RESULTS We obtained more than 85 % DE cells as shown with FACS analysis using antibodies directed against the DE marker CXCR4. In addition, biochemical and molecular analysis of bona-fide DE markers revealed a time-course induction of Sox17, CXCR4, and FoxA2. Focused PCR-based array also indicated a specific induction into the DE lineage. CONCLUSIONS In this study, we report an efficient serum-free protocol to differentiate WJ-MSCs into DE cells utilizing 3D spheroid formation. Our approach might aid in the development of new protocols to obtain DE-derivative lineages including liver-like and pancreatic insulin-producing cells.
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Affiliation(s)
| | - Hamad Ali
- Research Division, Dasman Diabetes Institute, 1180 Dasman, Kuwait
- Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Health Sciences Center, Kuwait University, Al-Jabriya, Kuwait
| | - Sarah AlKandari
- Research Division, Dasman Diabetes Institute, 1180 Dasman, Kuwait
| | | | - Nadeem Akhter
- Research Division, Dasman Diabetes Institute, 1180 Dasman, Kuwait
| | - Fahd Al-Mulla
- Department of Pathology, Molecular Pathology Unit, Faculty of Medicine, Health Sciences Center, Kuwait University, Al-Jabriya, Kuwait
| | - Maher Atari
- UIC Regenerative Medicine Research Institute, International University of Catalonia, Barcelona, Spain
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Selim AO, Selim SA, Shalaby SM, Mosaad H, Saber T. Neuroprotective effects of placenta-derived mesenchymal stromal cells in a rat model of experimental autoimmune encephalomyelitis. Cytotherapy 2016; 18:1100-13. [DOI: 10.1016/j.jcyt.2016.06.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 05/27/2016] [Accepted: 06/01/2016] [Indexed: 01/08/2023]
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Sarang S, Viswanathan C. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy. Int J Stem Cells 2016; 9:60-9. [PMID: 27426087 PMCID: PMC4961105 DOI: 10.15283/ijsc.2016.9.1.60] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2016] [Indexed: 01/04/2023] Open
Abstract
Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes.
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Affiliation(s)
- Shabari Sarang
- Reliance Life Sciences Pvt Ltd., Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, India
| | - Chandra Viswanathan
- Reliance Life Sciences Pvt Ltd., Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, India
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Advances in the Treatment of Ischemic Diseases by Mesenchymal Stem Cells. Stem Cells Int 2016; 2016:5896061. [PMID: 27293445 PMCID: PMC4886089 DOI: 10.1155/2016/5896061] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Accepted: 04/12/2016] [Indexed: 12/13/2022] Open
Abstract
Ischemic diseases are a group of diseases, including ischemic cerebrovascular disease, ischemic cardiomyopathy (ICM), and diabetic foot as well as other diseases which are becoming a leading cause of morbidity and mortality in the whole world. Mesenchymal stem cells (MSCs) have been used to treat a variety of ischemic diseases in animal models and clinical trials. Lots of recent publications demonstrated that MSCs therapy was safe and relieved symptoms in patients of ischemic disease. However, many factors could influence therapeutic efficacy including route of delivery, MSCs' survival and residential rate in vivo, timing of transplantation, particular microenvironment, and patient's clinical condition. In this review, the current status, therapeutic potential, and the detailed factors of MSCs-based therapeutics for ischemic cerebrovascular disease, ICM, and diabetic foot are presented and discussed. We think that MSCs transplantation would constitute an ideal option for patients with ischemic diseases.
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Current View on Osteogenic Differentiation Potential of Mesenchymal Stromal Cells Derived from Placental Tissues. Stem Cell Rev Rep 2016; 11:570-85. [PMID: 25381565 PMCID: PMC4493719 DOI: 10.1007/s12015-014-9569-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Mesenchymal stromal cells (MSC) isolated from human term placental tissues possess unique characteristics, including their peculiar immunomodulatory properties and their multilineage differentiation potential. The osteogenic differentiation capacity of placental MSC has been widely disputed, and continues to be an issue of debate. This review will briefly discuss the different MSC populations which can be obtained from different regions of human term placenta, along with their unique properties, focusing specifically on their osteogenic differentiation potential. We will present the strategies used to enhance osteogenic differentiation potential in vitro, such as through the selection of subpopulations more prone to differentiate, the modification of the components of osteo-inductive medium, and even mechanical stimulation. Accordingly, the applications of three-dimensional environments in vitro and in vivo, such as non-synthetic, polymer-based, and ceramic scaffolds, will also be discussed, along with results obtained from pre-clinical studies of placental MSC for the regeneration of bone defects and treatment of bone-related diseases.
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Balaji S, Zhou Y, Ganguly A, Opara EC, Soker S. The combined effect of PDX1, epidermal growth factor and poly-L-ornithine on human amnion epithelial cells' differentiation. BMC DEVELOPMENTAL BIOLOGY 2016; 16:8. [PMID: 27068127 PMCID: PMC4828805 DOI: 10.1186/s12861-016-0108-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 04/01/2016] [Indexed: 12/22/2022]
Abstract
Background It has been suggested that the ectopic expression of PDX1, a dominant pancreatic transcription factor, plays a critical role in the developmental programming of the pancreas even from cells of unrelated tissues such as keratinocytes and amniotic fluid stem cells. In this study we have chosen to drive pancreatic development in human amnion epithelial cells by inducing endogenous PDX1 expression. Further, we have investigated the role of Epidermal Growth Factor (EGF) and Poly-L-Ornithine (PLO) on this differentiation process. Results Human amnion epithelial cells expressed high levels of endogenous PDX1 upon transduction with an adenoviral vector expressing murine Pdx1. Other markers of various stages of pancreatic differentiation such as NKX6.1, SOX17, RFX6, FOXA2, CFTR, NEUROD1, PAX4 and PPY were also expressed upon Pdx1 transduction. Although initial expression of pancreatic progenitor markers was higher in culture conditions lacking EGF, for a sustained and increased expression EGF was required. Culture on PLO further increased the positive impact of EGF. Conclusion Pancreatic marker expression subsequent to mPdx1 transduction suggests that this approach may facilitate the in vitro differentiation of hAECs into cells of the endocrine pancreas. This result may have important implications in diabetes therapy. Electronic supplementary material The online version of this article (doi:10.1186/s12861-016-0108-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shruti Balaji
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, 27101, USA.,Birla Institute of Technology & Science, Pilani K K Birla Goa campus, Zuari Nagar, 403726, Goa, India
| | - Yu Zhou
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, 27101, USA
| | - Anasuya Ganguly
- Birla Institute of Technology & Science, Pilani K K Birla Goa campus, Zuari Nagar, 403726, Goa, India.
| | - Emmanuel C Opara
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, 27101, USA.,Virginia Tech-Wake Forest University School of Biomedical Engineering & Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
| | - Shay Soker
- Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, 27101, USA.,Virginia Tech-Wake Forest University School of Biomedical Engineering & Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA
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Abd-Allah SH, El-Shal AS, Shalaby SM, Abd-Elbary E, Mazen NF, Abdel Kader RR. The role of placenta-derived mesenchymal stem cells in healing of induced full-thickness skin wound in a mouse model. IUBMB Life 2015; 67:701-9. [PMID: 26315141 DOI: 10.1002/iub.1427] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 08/05/2015] [Accepted: 08/14/2015] [Indexed: 12/24/2022]
Abstract
We examined the effect of placenta-derived MSCs (PDMSCs) injection intraregionally and intraperitoneally on healing of induced full thickness mice skin wounds; moreover, the mechanisms by which MSCs exert their effects were also studied. Sixty female mice were divided into three groups after induction of full thickness skin wound; untreated group, wounded mice were injected with MSCs derived from human placenta intraperitoneally or intraregionally. Skin biopsies were obtained 7 and 12 days after wound incision for histological examinations, detection of vascular endothelial growth factor (VEGF) by ELISA, and estimation of expression of mouse ICAM-1, Integrin β1, Integrin β3 genes and human albumin and GAPDH genes by reverse transcription polymerase chain reaction. Human placenta derived-MSCs treated groups showed accelerated wound healing than non-treated group. VEGF, Integrin β1, and Integrin β3 levels were significantly increased in the intraregionally and intraperitoneally treated mice as compared to non-treated group at day 7 after wound induction. ICAM-1 showed significant decrease in its expression in treated groups compared with non-treated group. Interestingly, the intraperitoneal MSCs injections showed better results than intraregional one. PDMSCs accelerate full thickness skin wound healing and the intraperitoneal MSCs injections are more effective than intraregional one. MSCs promote wound healing through release of proangiogenic factors as VEGF, increase healing promoting factors as integrin β1 and β3, and decrease proinflammatory cytokines as ICAM-1.
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Affiliation(s)
- Somia H Abd-Allah
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Amal S El-Shal
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Sally M Shalaby
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Eman Abd-Elbary
- Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Nehad F Mazen
- Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Rania R Abdel Kader
- Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century. Stem Cells Int 2015; 2015:734731. [PMID: 26300923 PMCID: PMC4537770 DOI: 10.1155/2015/734731] [Citation(s) in RCA: 111] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 04/22/2015] [Accepted: 05/24/2015] [Indexed: 02/07/2023] Open
Abstract
Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ's reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC.
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Nekoei SM, Azarpira N, Sadeghi L, Kamalifar S. In vitro differentiation of human umbilical cord Wharton’s jelly mesenchymal stromal cells to insulin producing clusters. World J Clin Cases 2015; 3:640-649. [PMID: 26244156 PMCID: PMC4517339 DOI: 10.12998/wjcc.v3.i7.640] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Revised: 04/23/2015] [Accepted: 05/18/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the differentiation of human Wharton’s jelly derived mesenchymal stromal cells (WJ-MSCs) to insulin producing clusters (IPC) this study was conducted.
METHODS: The umbilical cords samples were collected from full term caesarian section mothers and the WJ-MSCS were cultured from tissue explants in High glucose-Dulbecco’s Modified Eagle Medium (H-DMEM); H-DMEM supplemented with 10% fetal bovine serum (FBS) and antibiotics. The expression of CD90, CD44, CD105, CD34 and CD133 as well as osteogenic and adipogenic differentiation of cells in appropriate medium were also evaluated. The cells were differentiated toward IPC with changing the culture medium and adding the small molecules such as nicotinic acid, epidermal growth factor, and exendin-4 during 3 wk period. The gene expression of PDX1, NGN3, Glut2, insulin was monitored by reveres transcription polymerase chain reaction method. The differentiated clusters were stained with Dithizone (DTZ) which confirms the presence of insulin granules. The insulin challenge test (low and high glucose concentration in Krebs-Ringer HEPES buffer) was also used to evaluate the functional properties of differentiated clusters.
RESULTS: WJ-MSCS were positive for mesenchymal surface markers (CD90, CD44, CD105), and negative for CD34 and CD133. The accumulation of lipid vacuoles and deposition of calcium mineral in cells were considered as adipogenic and osteogenic potential of WJ-MSCS. The cells also expressed the transcriptional factors such as Nanog and OCT4. During this three step differentiation, the WJ-MSCS morphology was gradually changed from spindle shaped cells in to epithelioid cells and eventually to three dimensional clusters. The clusters expressed PDX1, NGN3, Glut2, and insulin. The cells became bright red color when stained with DTZ and the insulin secretion was also confirmed. In glucose challenge test a significant increase in insulin secretion from 0.91 ± 0.04 μIu/mL (2.8 mmol/L glucose) to to 8.34 ± 0.45 μIu/mL (16.7 mmol/L glucose) was recorded (P < 0.05). The insulin secretion of undifferentiated WJ-MSCS was not changed in this challenge test.
CONCLUSION: WJ-MSCs have the ability to differentiate in to islet-like cells in vitro. However, this process needs further optimization in order to generate efficient and functional IPCs.
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Venugopal C, Chandanala S, Prasad HC, Nayeem D, Bhonde RR, Dhanushkodi A. Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies. J Tissue Eng Regen Med 2015; 11:321-333. [PMID: 26118731 DOI: 10.1002/term.2052] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 04/08/2015] [Accepted: 04/29/2015] [Indexed: 12/30/2022]
Abstract
Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by-products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.
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Affiliation(s)
- Chaitra Venugopal
- School of Regenerative Medicine, Manipal University, Bangalore, India
| | | | | | - Danish Nayeem
- School of Regenerative Medicine, Manipal University, Bangalore, India
| | - Ramesh R Bhonde
- School of Regenerative Medicine, Manipal University, Bangalore, India
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Oliveira MS, Barreto-Filho JB. Placental-derived stem cells: Culture, differentiation and challenges. World J Stem Cells 2015; 7:769-775. [PMID: 26029347 PMCID: PMC4444616 DOI: 10.4252/wjsc.v7.i4.769] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 12/17/2014] [Accepted: 04/14/2015] [Indexed: 02/06/2023] Open
Abstract
Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues (bone marrow, adipose tissue, and placenta) are potentially sources of stem cells. Placenta-derived stem cells (p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture (mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations (after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice.
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Jian RL, Mao LB, Xu Y, Li XF, Wang FP, Luo XG, Zhou H, He HP, Wang N, Zhang TC. Generation of insulin-producing cells from C3H10T1/2 mesenchymal progenitor cells. Gene 2015; 562:107-116. [PMID: 25724395 DOI: 10.1016/j.gene.2015.02.061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 02/10/2015] [Accepted: 02/18/2015] [Indexed: 12/29/2022]
Abstract
Mesenchymal stem cells (MSCs) have been reported to be an attractive source for the generation of transplantable surrogate β cells. A murine embryonic mesenchymal progenitor cell line C3H10T1/2 has been recognized as a model for MSCs, because of its multi-lineage differentiation potential. The purpose of this study was to explore whether C3H/10T1/2 cells have the potential to differentiate into insulin-producing cells (IPCs). Here, we investigated and compared the in vitro differentiation of rat MSCs and C3H10T1/2 cells into IPCs. After the cells underwent IPC differentiation, the expression of differentiation markers were detected by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR (qRT-PCR) and Western blotting. The insulin secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Furthermore, these differentiated cells were transplanted into streptozotocin-induced diabetic mice and their biological functions were tested in vivo. This study reports a 2-stage method to generate IPCs from C3H10T1/2 cells. Under specific induction conditions for 7-8 days, C3H10T1/2 cells formed three-dimensional spheroid bodies (SBs) and secreted insulin, while generation of IPCs derived from rat MSCs required a long time (more than 2 weeks). Furthermore, these IPCs derived from C3H10T1/2 cells were injected into diabetic mice and improves basal glucose, body weight and exhibited normal glucose tolerance test. The present study provided a simple and faithful in vitro model for further investigating the mechanism underlying IPC differentiation of MSCs and cell replacement therapy for diabetes.
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Affiliation(s)
- Ruo-Lei Jian
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Li-Bin Mao
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Yao Xu
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Xiao-Fan Li
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Feng-Po Wang
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Xue-Gang Luo
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Hao Zhou
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Hong-Peng He
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China
| | - Nan Wang
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
| | - Tong-Cun Zhang
- Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China; Department of Biochemistry, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China.
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