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Keshavarz S, Alavi CE, Aghayan H, Jafari-Shakib R, Vojoudi E. Advancements in Degenerative Disc Disease Treatment: A Regenerative Medicine Approach. Stem Cell Rev Rep 2025:10.1007/s12015-025-10882-z. [PMID: 40232618 DOI: 10.1007/s12015-025-10882-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2025] [Indexed: 04/16/2025]
Abstract
Regenerative medicine represents a transformative approach to treating nucleus pulposus degeneration and offers hope for patients suffering from chronic low back pain due to disc degeneration. By focusing on restoring the natural structure and function of the nucleus pulposus rather than merely alleviating symptoms, these innovative therapies hold the potential to significantly improve patient outcomes. As research continues to advance in this field, we may soon witness a paradigm shift in how we approach spinal health and degenerative disc disease. The main purpose of this review is to provide an overview of the various regenerative approaches that target the restoration of the nucleus pulposus, a primary site for initiation of intervertebral disc degeneration.
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Affiliation(s)
- Samaneh Keshavarz
- School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Cyrus Emir Alavi
- Department of Anesthesiology, Neuroscience Research Center, Avicenna University Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Hamidreza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Jafari-Shakib
- Department of Immunology, School of Medicine, Guilan University of Medical Sciences, P.O.Box 41635 - 3363, Rasht, Iran.
| | - Elham Vojoudi
- Regenerative Medicine, Organ Procurement and Transplantation Multidisciplinary Center, School of Medicine, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran.
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Allouh MZ, Rizvi SFA, Alamri A, Jimoh Y, Aouda S, Ouda ZH, Hamad MIK, Perez-Cruet M, Chaudhry GR. Mesenchymal stromal/stem cells from perinatal sources: biological facts, molecular biomarkers, and therapeutic promises. Stem Cell Res Ther 2025; 16:127. [PMID: 40055783 PMCID: PMC11889844 DOI: 10.1186/s13287-025-04254-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 02/25/2025] [Indexed: 05/13/2025] Open
Abstract
The use of mesenchymal stem cells (MSCs) from perinatal tissue sources has gained attention due to their availability and lack of significant ethical or moral concerns. These cells have a higher proliferative capability than adult MSCs and less immunogenic or tumorigenesis risk than fetal and embryonic stem cells. Additionally, they do not require invasive isolation methods like fetal and adult MSCs. We reviewed the main biological and therapeutic aspects of perinatal MSCs in a three-part article. In the first part, we revised the main biological features and characteristics of MSCs and the advantages of perinatal MSCs over other types of SCs. In the second part, we provided a detailed molecular background for the main biomarkers that can be used to identify MSCs. In the final part, we appraised the therapeutic application of perinatal MSCs in four major degenerative disorders: degenerative disc disease, retinal degenerative diseases, ischemic heart disease, and neurodegenerative diseases. In conclusion, there is no single specific molecular marker to identify MSCs. We recommend using at least two positive markers of stemness (CD29, CD73, CD90, or CD105) and two negative markers (CD34, CD45, or CD14) to exclude the hematopoietic origin. Moreover, utilizing perinatal MSCs for managing degenerative diseases presents a promising therapeutic approach. This review emphasizes the significance of employing more specialized progenitor cells that originated from the perinatal MSCs. The review provides scientific evidence from the literature that applying these progenitor cells in therapeutic procedures provides a greater regenerative capacity than the original primitive MSCs. Finally, this review provides a valuable reference for researchers exploring perinatal MSCs and their therapeutic applications.
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Affiliation(s)
- Mohammed Z Allouh
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P. O. Box: 15551, Al Ain, UAE.
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA.
| | - Syed Faizan Ali Rizvi
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA
| | - Ali Alamri
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA
| | - Yusuf Jimoh
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA
| | - Salma Aouda
- College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE
| | - Zakaria H Ouda
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P. O. Box: 15551, Al Ain, UAE
| | - Mohammad I K Hamad
- Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P. O. Box: 15551, Al Ain, UAE
| | - Mick Perez-Cruet
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA
- Department of Neurosurgery, Corewell Health, Royal Oak, MI, USA
| | - G Rasul Chaudhry
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, 48309, USA.
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA.
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Chen X, Li H, Huang B, Ruan J, Li X, Li Q. High impact works on stem cell transplantation in intervertebral disc degeneration. BMC Musculoskelet Disord 2024; 25:1029. [PMID: 39702055 DOI: 10.1186/s12891-024-08131-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/29/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND Low back pain is a major disorder that causes disability and is strongly associated with intervertebral disc degeneration (IDD). Because of the limitations of contemporary interventions, stem cell transplantation (SCT) has been increasingly used to regenerate degenerative discs. Nevertheless, analyses of high-impact papers in this field are rare. This study aimed to determine and analyze the 100 highest-cited documents on SCT in IDD. METHODS The 100 highest-cited documents were retrieved from the Web of Science (WoS) database. Descriptive statistics were calculated and correlation analysis was conducted to determine the relationship between WoS citations, the Altmetric Attention Score (AAS), and Dimensions citations. RESULTS The citation counts of the top 100 most cited papers ranged from 13 to 372. These studies were conducted in 17 countries and were published in 48 journals between 2003 and 2021. The top three contributing countries were the China (31), United States (22), and Japan (14). Bone marrow-derived stem cells were the most common type of stem cells (70.00%), followed by adipose-derived stem cells (13.75%), and nucleus pulposus-derived stem cells (7.50). Rabbit was the most studied species (41.25%), followed by rat (21.25%), human (13.75%), sheep (8.75%), dog (8.75%), and pig (6.25%). Tokai University School of Medicine (11) had the largest number of documents, followed by The University of Hong Kong (8), and Southeast University (4). Sakai D (10) was the most fruitful author, followed by Cheung KMC (6), Melrose J (3), Pettine K (3), Lotz JC (3), and Murphy MB (3). We observed a very high correlation between the WoS and Dimensions citations (p < 0.001, r = 0.994). CONCLUSIONS This study highlights the highest impact works on SCT in IDD, thereby providing a deeper understanding of the historical works related to SCT in IDD, as well as benefits for future studies in this field.
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Affiliation(s)
- Xiaofeng Chen
- Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, China
| | - Hao Li
- Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, China
| | - Baoci Huang
- Department of Ultrasound, Guangdong Second Provincial General Hospital Guangzhou City, Guangzhou, China
| | - Jiajian Ruan
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xi Li
- Department of Dermatology, Panyu Hospital of Chinese Medicine, Guangzhou, China.
| | - Qian Li
- Guangzhou University of Chinese Medicine, Guangzhou, China.
- Department of Dermatology, Panyu Hospital of Chinese Medicine, Guangzhou, China.
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Ramzan F, Salim A, Hussain A, Khan I. Unleashing the Healing Power of Mesenchymal Stem Cells for Osteochondral Abnormalities. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2024. [DOI: 10.1007/s40883-024-00356-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/25/2024] [Accepted: 08/31/2024] [Indexed: 01/11/2025]
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Huang H, Liu X, Wang J, Suo M, Zhang J, Sun T, Zhang W, Li Z. Umbilical cord mesenchymal stem cells for regenerative treatment of intervertebral disc degeneration. Front Cell Dev Biol 2023; 11:1215698. [PMID: 37601097 PMCID: PMC10439242 DOI: 10.3389/fcell.2023.1215698] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/27/2023] [Indexed: 08/22/2023] Open
Abstract
Intervertebral disc degeneration is thought to be a major contributor to low back pain, the etiology of which is complex and not yet fully understood. To compensate for the lack of drug and surgical treatment, mesenchymal stem cells have been proposed for regenerative treatment of intervertebral discs in recent years, and encouraging results have been achieved in related trials. Mesenchymal stem cells can be derived from different parts of the body, among which mesenchymal stem cells isolated from the fetal umbilical cord have excellent performance in terms of difficulty of acquisition, differentiation potential, immunogenicity and ethical risk. This makes it possible for umbilical cord derived mesenchymal stem cells to replace the most widely used bone marrow-derived and adipose tissue derived mesenchymal stem cells as the first choice for regenerating intervertebral discs. However, the survival of umbilical cord mesenchymal stem cells within the intervertebral disc is a major factor affecting their regenerative capacity. In recent years biomaterial scaffolds in tissue engineering have aided the survival of umbilical cord mesenchymal stem cells by mimicking the natural extracellular matrix. This seems to provide a new idea for the application of umbilical cord mesenchymal stem cells. This article reviews the structure of the intervertebral disc, disc degeneration, and the strengths and weaknesses of common treatment methods. We focus on the cell source, cell characteristics, mechanism of action and related experiments to summarize the umbilical cord mesenchymal stem cells and explore the feasibility of tissue engineering technology of umbilical cord mesenchymal stem cells. Hoping to provide new ideas for the treatment of disc degeneration.
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Affiliation(s)
- Huagui Huang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xin Liu
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jinzuo Wang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Moran Suo
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jing Zhang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Tianze Sun
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Wentao Zhang
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zhonghai Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic Diseases, Dalian, Liaoning, China
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He S, Wu H, Huang J, Li Q, Huang Z, Wen H, Li Z. 3-D tissue-engineered epidermis against human primary keratinocytes apoptosis via relieving mitochondrial oxidative stress in wound healing. J Tissue Eng 2023; 14:20417314231163168. [PMID: 37025157 PMCID: PMC10071207 DOI: 10.1177/20417314231163168] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 02/24/2023] [Indexed: 04/03/2023] Open
Abstract
The tissue-engineered epidermal (TEE), composed of biocompatible vectors and autogenous functional cells, is a novel strategy to solve the problem of shortage of donor skin sources. The human primary keratinocyte (HPK), the major skin components, are self-evident vital in wound healing and was considered as one of the preferred seed cells for TEEs. Since the process of separating HPKs from the skin triggers a stress state of the cells, achieving its rapid adhesion and proliferation on biomaterials remains challenging. The key to the clinical application is to ensure the normal function of cells while improving the proliferation ability in vitro, and to complete the complex mesenchymal epithelialization to achieve tissue remodeling after vivo implantation. Herein, in order to aid HPKs adhesion and proliferation in vitro and promoting wound healing, we developed a three dimensional collagen scaffold with Y-27632 sustainedly released from the nanoplatform, hollow mesoporous organosilica nanoparticles (HMON). The results showed that the porous structure within the TEE supports the implanted HPKs expanding in a three-dimensional mode to jointly construct the tissue-engineered epidermis in vitro and inhibited the mitochondria-mediated cell apoptosis. It was confirmed that the TEEs with suitable degradation rate could maintain drug release after implantation and could accelerate vascularization of wound base and further revealed the involvement of mesenchymal transformation of transplanted HPKs during skin regeneration in a nude mouse model with full-thickness skin resection. In conclusion, our study highlights the great potential of constructing TEE using a nanoparticle platform for the treatment of large-area skin defects.
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Affiliation(s)
- Shan He
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Han Wu
- Medical Research Center of Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junqun Huang
- Department of Anaesthesia, The Seventh Affiliated Hospital, Southern Medical University, Foshan, China
| | - Qingyan Li
- Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zijie Huang
- Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Huangding Wen
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhiqing Li
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Razzaq SS, Khan I, Naeem N, Salim A, Begum S, Haneef K. Overexpression of GATA binding protein 4 and myocyte enhancer factor 2C induces differentiation of mesenchymal stem cells into cardiac-like cells. World J Stem Cells 2022; 14:700-713. [PMID: 36188117 PMCID: PMC9516467 DOI: 10.4252/wjsc.v14.i9.700] [Citation(s) in RCA: 6] [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: 03/28/2022] [Revised: 06/20/2022] [Accepted: 08/30/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Heart diseases are the primary cause of death all over the world. Following myocardial infarction, billions of cells die, resulting in a huge loss of cardiac function. Stem cell-based therapies have appeared as a new area to support heart regeneration. The transcription factors GATA binding protein 4 (GATA-4) and myocyte enhancer factor 2C (MEF2C) are considered prominent factors in the development of the cardiovascular system. AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry, and by their potential to differentiate into osteocytes and adipocytes. hUC-MSCs were transfected with GATA-4, MEF2C, and their combination to direct the differentiation. Cardiac differentiation was confirmed by semiquantitative real-time polymerase chain reaction and immunocytochemistry. RESULTS hUC-MSCs expressed specific cell surface markers CD105, CD90, CD44, and vimentin but lack the expression of CD45. The transcription factors GATA-4 and MEF2C, and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e., GATA-4, MEF2C, NK2 homeobox 5 (NKX2.5), MHC, and connexin-43, and cardiac proteins GATA-4, NKX2.5, cardiac troponin T, and connexin-43. CONCLUSION Transfection with GATA-4, MEF2C, and their combination effectively induces cardiac differentiation in hUC-MSCs. These genetically modified MSCs could be a promising treatment option for heart diseases in the future.
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Affiliation(s)
- Syeda Saima Razzaq
- Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi 75270, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Nadia Naeem
- Dow Research Institute of Biotechnology & Biomedical Sciences (DRIBBS), Dow University of Health Sciences (DUHS), Ojha Campus, Karachi 75200, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Sumreen Begum
- Stem Cells Research Laboratory (SCRL), Sindh Institute of Urology and Transplantation (SIUT), Karachi 74200, Pakistan
| | - Kanwal Haneef
- Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi 75270, Pakistan.
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Bai B, Hou M, Hao J, Liu Y, Ji G, Zhou G. Research progress in seed cells for cartilage tissue engineering. Regen Med 2022; 17:659-675. [PMID: 35703020 DOI: 10.2217/rme-2022-0023] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Cartilage defects trouble millions of patients worldwide and their repair via conventional treatment is difficult. Excitingly, tissue engineering technology provides a promising strategy for efficient cartilage regeneration with structural regeneration and functional reconstruction. Seed cells, as biological prerequisites for cartilage regeneration, determine the quality of regenerated cartilage. The proliferation, differentiation and chondrogenesis of seed cells are greatly affected by their type, origin and generation. Thus, a systematic description of the characteristics of seed cells is necessary. This article reviews in detail the cellular characteristics, research progress, clinical translation challenges and future research directions of seed cells while providing guidelines for selecting appropriate seed cells for cartilage regeneration.
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Affiliation(s)
- Baoshuai Bai
- Research Institute of Plastic Surgery, Wei Fang Medical University, Wei Fang, Shandong, 261053, China.,Shanghai Key Laboratory of Tissue Engineering, Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China.,National Tissue Engineering Center of China, Shanghai, 200240, China
| | - Mengjie Hou
- Shanghai Key Laboratory of Tissue Engineering, Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China.,National Tissue Engineering Center of China, Shanghai, 200240, China
| | - Junxiang Hao
- Research Institute of Plastic Surgery, Wei Fang Medical University, Wei Fang, Shandong, 261053, China.,Shanghai Key Laboratory of Tissue Engineering, Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China.,National Tissue Engineering Center of China, Shanghai, 200240, China
| | - Yanhan Liu
- Shanghai JiaoTong University School of Medicine, Shanghai, 200240, China
| | - Guangyu Ji
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200240, China
| | - Guangdong Zhou
- Research Institute of Plastic Surgery, Wei Fang Medical University, Wei Fang, Shandong, 261053, China.,Shanghai Key Laboratory of Tissue Engineering, Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China.,National Tissue Engineering Center of China, Shanghai, 200240, China
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Perera D, Soysa P, Wijeratne S. A Comparison of Mesenchymal Stem Cell-derived Hepatocyte-like Cells and HepG2 Cells for Use in Drug-Induced Liver Injury Studies. Altern Lab Anim 2022; 50:146-155. [DOI: 10.1177/02611929221091269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Liver cell lines obtained from hepatomas, for example, HepG2 cells, are commonly used in drug toxicity studies. However, functional hepatocyte-like cells derived from mesenchymal stem cells (MSCs) could be a better option for use in the study of drug metabolism and toxicity. Overdose of acetaminophen (APAP) and excess alcohol consumption are common causes of liver damage. The objective of the present study was to investigate the use of MSC-derived hepatocyte-like cells (MSCdH) in the assessment of drug-induced liver injury (by using APAP and ethanol), and to compare the toxic effects observed in the MSCdH with those exhibited by HepG2 cells. MSCs were isolated from umbilical cord and their functionality confirmed by their ability to differentiate into adipocytes, osteocytes and hepatocyte-like cells. It was shown that the MSCs successfully differentiated into hepatocyte-like cells, and these cells were further characterised by using various enzyme assays and by assessing albumin secretion and urea synthesis. Cytotoxicity was evaluated in the HepG2 and MSCdH after exposure to ethanol and APAP, with cell viability being determined by using the MTT assay. After exposure to ethanol and to APAP, cell viability decreased in a concentration-dependent manner for both types of hepatocytes. The respective EC50 values of ethanol-induced toxicity for HepG2 and MSCdH cells were 2.5% and 1.3% v/v ( p < 0.001); for APAP-induced toxicity they were 19.1 mM and 12.6 mM ( p < 0.001). These findings show that there is a distinct difference between the two types of hepatocytes in terms of APAP-induced and ethanol-induced liver injury.
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Affiliation(s)
- Dananjaya Perera
- Department of Biochemistry and Molecular Biology, University of Colombo, Faculty of Medicine, Colombo, Sri Lanka
| | - Preethi Soysa
- Department of Biochemistry and Molecular Biology, University of Colombo, Faculty of Medicine, Colombo, Sri Lanka
| | - Sumedha Wijeratne
- Department of Obstetrics & Gynaecology, University of Colombo, Faculty of Medicine, Colombo, Sri Lanka
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Khalid S, Ekram S, Salim A, Chaudhry GR, Khan I. Transcription regulators differentiate mesenchymal stem cells into chondroprogenitors, and their in vivo implantation regenerated the intervertebral disc degeneration. World J Stem Cells 2022; 14:163-182. [PMID: 35432734 PMCID: PMC8963382 DOI: 10.4252/wjsc.v14.i2.163] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/02/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intervertebral disc degeneration (IVDD) is the leading cause of lower back pain. Disc degeneration is characterized by reduced cellularity and decreased production of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been envisioned as a promising treatment for degenerative illnesses. Cell-based therapy using ECM-producing chondrogenic derivatives of MSCs has the potential to restore the functionality of the intervertebral disc (IVD). AIM To investigate the potential of chondrogenic transcription factors to promote differentiation of human umbilical cord MSCs into chondrocytes, and to assess their therapeutic potential in IVD regeneration. METHODS MSCs were isolated and characterized morphologically and immunologically by the expression of specific markers. MSCs were then transfected with Sox-9 and Six-1 transcription factors to direct differentiation and were assessed for chondrogenic lineage based on the expression of specific markers. These differentiated MSCs were implanted in the rat model of IVDD. The regenerative potential of transplanted cells was investigated using histochemical and molecular analyses of IVDs. RESULTS Isolated cells showed fibroblast-like morphology and expressed CD105, CD90, CD73, CD29, and Vimentin but not CD45 antigens. Overexpression of Sox-9 and Six-1 greatly enhanced the gene expression of transforming growth factor beta-1 gene, BMP, Sox-9, Six-1, and Aggrecan, and protein expression of Sox-9 and Six-1. The implanted cells integrated, survived, and homed in the degenerated intervertebral disc. Histological grading showed that the transfected MSCs regenerated the IVD and restored normal architecture. CONCLUSION Genetically modified MSCs accelerate cartilage regeneration, providing a unique opportunity and impetus for stem cell-based therapeutic approach for degenerative disc diseases.
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Affiliation(s)
- Shumaila Khalid
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Sobia Ekram
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI 48309, United States
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan.
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11
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Application of stem cells in the repair of intervertebral disc degeneration. Stem Cell Res Ther 2022; 13:70. [PMID: 35148808 PMCID: PMC8832693 DOI: 10.1186/s13287-022-02745-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/25/2022] [Indexed: 12/16/2022] Open
Abstract
Intervertebral disc degeneration (IDD) is a common disease that increases with age, and its occurrence is stressful both psychologically and financially. Stem cell therapy for IDD is emerging. For this therapy, stem cells from different sources have been proven in vitro, in vivo, and in clinical trials to relieve pain and symptoms, reverse the degeneration cascade, delay the aging process, maintain the spine shape, and retain mechanical function. However, further research is needed to explain how stem cells play these roles and what effects they produce in IDD treatment. This review aims to summarize and objectively analyse the current evidence on stem cell therapy for IDD.
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12
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Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications. Stem Cells Int 2022; 2022:2454168. [PMID: 35035489 PMCID: PMC8758292 DOI: 10.1155/2022/2454168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/13/2021] [Accepted: 11/23/2021] [Indexed: 11/30/2022] Open
Abstract
Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.
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Williams RJ, Tryfonidou MA, Snuggs JW, Le Maitre CL. Cell sources proposed for nucleus pulposus regeneration. JOR Spine 2021; 4:e1175. [PMID: 35005441 PMCID: PMC8717099 DOI: 10.1002/jsp2.1175] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/01/2021] [Accepted: 10/20/2021] [Indexed: 12/13/2022] Open
Abstract
Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adipose-derived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.
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Affiliation(s)
- Rebecca J. Williams
- Biomedical Research Centre, BiosciencesSheffield Hallam UniversitySheffieldUK
| | - Marianna A. Tryfonidou
- Department of Clinical Sciences, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
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14
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Brown C, McKee C, Halassy S, Kojan S, Feinstein DL, Chaudhry GR. Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Stem Cell Res Ther 2021; 12:499. [PMID: 34503569 PMCID: PMC8427882 DOI: 10.1186/s13287-021-02563-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. There is no cure for MS. We used a novel approach to investigate the therapeutic potential of neural stem cells (NSCs) derived from human primitive mesenchymal stem cells (MSCs) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods MSCs were differentiated into NSCs, labeled with PKH26, and injected into the tail vein of EAE mice. Neurobehavioral changes in the mice assessed the effect of transplanted cells on the disease process. The animals were sacrificed two weeks following cell transplantation to collect blood, lymphatic, and CNS tissues for analysis. Transplanted cells were tracked in various tissues by flow cytometry. Immune infiltrates were determined and characterized by H&E and immunohistochemical staining, respectively. Levels of immune regulatory cells, Treg and Th17, were analyzed by flow cytometry. Myelination was determined by Luxol fast blue staining and immunostaining. In vivo fate of transplanted cells and expression of inflammation, astrogliosis, myelination, neural, neuroprotection, and neurogenesis markers were investigated by using immunohistochemical and qRT-PCR analysis.
Results MSC-derived NSCs expressed specific neural markers, NESTIN, TUJ1, VIMENTIN, and PAX6. NSCs improved EAE symptoms more than MSCs when transplanted in EAE mice. Post-transplantation analyses also showed homing of MSCs and NSCs into the CNS with concomitant induction of an anti-inflammatory response, resulting in reducing immune infiltrates. NSCs also modulated Treg and Th17 cell levels in EAE mice comparable to healthy controls. Luxol fast blue staining showed significant improvement in myelination in treated mice. Further analysis showed that NSCs upregulated genes involved in myelination and neuroprotection but downregulated inflammatory and astrogliosis genes more significantly than MSCs. Importantly, NSCs differentiated into neural derivatives and promoted neurogenesis, possibly by modulating BDNF and FGF signaling pathways. Conclusions NSC transplantation reversed the disease process by inducing an anti-inflammatory response and promoting myelination, neuroprotection, and neurogenesis in EAE disease animals. These promising results provide a basis for clinical studies to treat MS using NSCs derived from primitive MSCs. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02563-8.
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Affiliation(s)
- Christina Brown
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA.,OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, MI, 48309, USA
| | - Christina McKee
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA.,OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, MI, 48309, USA
| | - Sophia Halassy
- Ascension Providence Hospital, Southfield, MI, 48075, USA
| | - Suleiman Kojan
- Department of Neuroscience, OUWB School of Medicine, Oakland University, Rochester, MI, 48309, USA
| | - Doug L Feinstein
- Department of Anesthesiology, The University of Illinois at Chicago, Chicago, IL, 60607, USA.,Department of Veterans Affairs, Jesse Brown VA Medical Center, Chicago, IL, 60612, USA
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA. .,OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, MI, 48309, USA.
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15
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Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther 2020; 11:492. [PMID: 33225992 PMCID: PMC7681994 DOI: 10.1186/s13287-020-02001-1] [Citation(s) in RCA: 157] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/27/2020] [Indexed: 12/15/2022] Open
Abstract
Skeletal disorders are among the leading debilitating factors affecting millions of people worldwide. The use of stem cells for tissue repair has raised many promises in various medical fields, including skeletal disorders. Mesenchymal stem cells (MSCs) are multipotent stromal cells with mesodermal and neural crest origin. These cells are one of the most attractive candidates in regenerative medicine, and their use could be helpful in repairing and regeneration of skeletal disorders through several mechanisms including homing, angiogenesis, differentiation, and response to inflammatory condition. The most widely studied sources of MSCs are bone marrow (BM), adipose tissue, muscle, umbilical cord (UC), umbilical cord blood (UCB), placenta (PL), Wharton's jelly (WJ), and amniotic fluid. These cells are capable of differentiating into osteoblasts, chondrocytes, adipocytes, and myocytes in vitro. MSCs obtained from various sources have diverse capabilities of secreting many different cytokines, growth factors, and chemokines. It is believed that the salutary effects of MSCs from different sources are not alike in terms of repairing or reformation of injured skeletal tissues. Accordingly, differential identification of MSCs' secretome enables us to make optimal choices in skeletal disorders considering various sources. This review discusses and compares the therapeutic abilities of MSCs from different sources for bone and cartilage diseases.
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Affiliation(s)
- Parisa Kangari
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tahereh Talaei-Khozani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Tissue Engineering Laboratory, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mahboobeh Razmkhah
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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16
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Ramallo M, Carreras-Sánchez I, López-Fernández A, Vélez R, Aguirre M, Feldman S, Vives J. Advances in translational orthopaedic research with species-specific multipotent mesenchymal stromal cells derived from the umbilical cord. Histol Histopathol 2020; 36:19-30. [PMID: 32914860 DOI: 10.14670/hh-18-249] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Compliance with current regulations for the development of innovative medicines require the testing of candidate therapies in relevant translational animal models prior to human use. This poses a great challenge when the drug is composed of cells, not only because of the living nature of the active ingredient but also due to its human origin, which can subsequently lead to a xenogeneic response in the animals. Although immunosuppression is a plausible solution, this is not suitable for large animals and may also influence the results of the study by altering mechanisms of action that are, in fact, poorly understood. For this reason, a number of procedures have been developed to isolate homologous species-specific cell types to address preclinical pharmacodynamics, pharmacokinetics and toxicology. In this work, we present and discuss advances in the methodologies for derivation of multipotent Mesenchymal Stromal Cells derived from the umbilical cord, in general, and Wharton's jelly, in particular, from medium to large animals of interest in orthopaedics research, as well as current and potential applications in studies addressing proof of concept and preclinical regulatory aspects.
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Affiliation(s)
- Melina Ramallo
- School of Medicine, LABOATEM, - Osteoarticular Biology, Tissue Engineering and Emerging Therapies Laboratory, Biological Chemistry Cat., School of Medicine, National Rosario University, Rosario, Argentina
| | | | - Alba López-Fernández
- Servei de Teràpia Cellular, Banc de Sang i Teixits, Barcelona, Spain.,Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Roberto Vélez
- Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.,Orthopedic Surgery Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
| | - Màrius Aguirre
- Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.,Orthopedic Surgery Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
| | - Sara Feldman
- School of Medicine, LABOATEM, - Osteoarticular Biology, Tissue Engineering and Emerging Therapies Laboratory, Biological Chemistry Cat., School of Medicine, National Rosario University, Argentina.,Researh Council of the Rosario National University, (CIUNR) and CONICET, Rosario, Argentina.
| | - Joaquim Vives
- Servei de Teràpia Cellular, Banc de Sang i Teixits, Barcelona, Spain.,Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.,Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
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17
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Ali SR, Ahmad W, Naeem N, Salim A, Khan I. Small molecule 2'-deoxycytidine differentiates human umbilical cord-derived MSCs into cardiac progenitors in vitro and their in vivo xeno-transplantation improves cardiac function. Mol Cell Biochem 2020; 470:99-113. [PMID: 32415417 DOI: 10.1007/s11010-020-03750-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 05/08/2020] [Indexed: 12/11/2022]
Abstract
Small molecules are widely used to induce stem cell differentiation. 2'-deoxycytidine (2-DC) belongs to the cytidine family. It stimulates the expression of cardiac-specific genes and proteins, and directs mesenchymal stem cells towards cardiomyogenic differentiation. We aim to investigate the role of 2-DC-treated human umbilical cord mesenchymal stem cells (UC-MSCs) into myogenic lineage and explore their application in regeneration of infarcted myocardium. UC-MSCs were treated with 5, 10, 20, and 40 µM 2-DC following optimization by cytotoxicity analysis. Rat model of myocardial infarction (MI) was induced by ligating left anterior descending coronary artery. Normal, and 2-DC treated UC-MSCs were transplanted in the left ventricular wall immediately after ligation. Echocardiographic measurements were performed to assess cardiac function. Tissue architecture of the myocardium was examined by histological analysis to determine fate of the transplanted cells. MSCs were successfully isolated from human umbilical cord tissue. 2-DC treatment did not produce any significant cytotoxic effect in UC-MSCs at all concentrations. qPCR analysis of treated UC-MSCs showed induction of myogenic differentiation, which is more pronounced at 20 μM concentration. Fluorescently labeled 2-DC-treated UC-MSCs showed significant (**P < 0.01) homing in the infarcted myocardium as compared to normal UC-MSCs. Hearts transplanted with 2-DC-treated UC-MSCs significantly (***P < 0.001) improved the cardiac systolic and diastolic functions and pumping ability as compared to normal UC-MSCs and MI groups. Fibrotic area and left ventricular wall thickness were significantly improved (***P < 0.001) in 2-DC-treated group as compared to normal UC-MSCs. Immunohistochemical staining showed co-localization of fluorescently labeled cells and patches of differentiated myocytes which were stained for cardiac proteins in the infarct zone implying that the treated UC-MSCs regenerated cardiomyocytes. We report for the first time that 2-DC induces cardiac differentiation in UC-MSCs. Transplanted cells differentiated into functional cardiomyocytes and significantly improved cardiac performance. These pre-differentiated cardiac progenitors showed better survival, homing, and distribution in the infarcted zone. 2-DC treated cells not only improved cardiac function, but also restored tissue homeostasis, suggesting a better therapeutic option for the regeneration of cardiac tissue in the clinical setup.
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Affiliation(s)
- Syeda Roohina Ali
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Waqas Ahmad
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Nadia Naeem
- Dow University of Health Sciences, Ojha Campus, Gulzar-e-Hijri, Suparco Road, KDA Scheme-33, Karachi, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
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18
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Brown C, McKee C, Bakshi S, Walker K, Hakman E, Halassy S, Svinarich D, Dodds R, Govind CK, Chaudhry GR. Mesenchymal stem cells: Cell therapy and regeneration potential. J Tissue Eng Regen Med 2019; 13:1738-1755. [PMID: 31216380 DOI: 10.1002/term.2914] [Citation(s) in RCA: 372] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/15/2019] [Accepted: 06/07/2019] [Indexed: 12/12/2022]
Abstract
Rapid advances in the isolation of multipotent progenitor cells, routinely called mesenchymal stromal/stem cells (MSCs), from various human tissues and organs have provided impetus to the field of cell therapy and regenerative medicine. The most widely studied sources of MSCs include bone marrow, adipose, muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid. According to the standard definition of MSCs, these clonal cells adhere to plastic, express cluster of differentiation (CD) markers such as CD73, CD90, and CD105 markers, and can differentiate into adipogenic, chondrogenic, and osteogenic lineages in vitro. However, isolated MSCs have been reported to vary in their potency and self-renewal potential. As a result, the MSCs used for clinical applications often lead to variable or even conflicting results. The lack of uniform characterization methods both in vitro and in vivo also contributes to this confusion. Therefore, the name "MSCs" itself has been increasingly questioned lately. As the use of MSCs is expanding rapidly, there is an increasing need to understand the potential sources and specific potencies of MSCs. This review discusses and compares the characteristics of MSCs and suggests that the variations in their distinctive features are dependent on the source and method of isolation as well as epigenetic changes during maintenance and growth. We also discuss the potential opportunities and challenges of MSC research with the hope to stimulate their use for therapeutic and regenerative medicine.
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Affiliation(s)
- Christina Brown
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Christina McKee
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Shreeya Bakshi
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Keegan Walker
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Eryk Hakman
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - Sophia Halassy
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - David Svinarich
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
- Ascension Providence Hospital, Southfield, MI, USA
| | - Robert Dodds
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - Chhabi K Govind
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
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19
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Perez-Cruet M, Beeravolu N, McKee C, Brougham J, Khan I, Bakshi S, Chaudhry GR. Potential of Human Nucleus Pulposus-Like Cells Derived From Umbilical Cord to Treat Degenerative Disc Disease. Neurosurgery 2019; 84:272-283. [PMID: 29490072 PMCID: PMC6292795 DOI: 10.1093/neuros/nyy012] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 01/09/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Degenerative disc disease (DDD) is a common spinal disorder that manifests with neck and lower back pain caused by the degeneration of intervertebral discs (IVDs). Currently, there is no treatment to cure this debilitating ailment. OBJECTIVE To investigate the potential of nucleus pulposus (NP)-like cells (NPCs) derived from human umbilical cord mesenchymal stem cells (MSCs) to restore degenerated IVDs using a rabbit DDD model. METHODS NPCs differentiated from MSCs were characterized using quantitative real-time reverse transcription polymerase chain reaction and immunocytochemical analysis. MSCs and NPCs were labeled with fluorescent dye, PKH26, and transplanted into degenerated IVDs of a rabbit model of DDD (n = 9 each). Magnetic resonance imaging of the IVDs was performed before and after IVD degeneration, and following cell transplantation. IVDs were extracted 8 wk post-transplantation and analyzed by various biochemical, immunohistological, and molecular techniques. RESULTS NPC derivatives of MSCs expressed known NP-specific genes, SOX9, ACAN, COL2, FOXF1, and KRT19. Transplanted cells survived, dispersed, and integrated into the degenerated IVDs. IVDs augmented with NPCs showed significant improvement in the histology, cellularity, sulfated glycosaminoglycan and water contents of the NP. In addition, expression of human genes, SOX9, ACAN, COL2, FOXF1, KRT19, PAX6, CA12, and COMP, as well as proteins, SOX9, ACAN, COL2, and FOXF1, suggest NP biosynthesis due to transplantation of NPCs. Based on these results, a molecular mechanism for NP regeneration was proposed. CONCLUSION The findings of this study demonstrating feasibility and efficacy of NPCs to regenerate NP should spur interest for clinical studies to treat DDD using cell therapy.
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Affiliation(s)
- Mick Perez-Cruet
- Department of Neurosurgery, Beaumont Health System, Royal Oak, Michigan
- OUWB School of Medicine, Oakland University, Rochester, Michigan
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Michigan Head and Spine Institute, Southfield, Michigan
| | - Naimisha Beeravolu
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Department of Biological Sciences, Oakland University, Rochester, Michigan
| | - Christina McKee
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Department of Biological Sciences, Oakland University, Rochester, Michigan
| | - Jared Brougham
- OUWB School of Medicine, Oakland University, Rochester, Michigan
| | - Irfan Khan
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Department of Biological Sciences, Oakland University, Rochester, Michigan
- Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Shreeya Bakshi
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Department of Biological Sciences, Oakland University, Rochester, Michigan
| | - G Rasul Chaudhry
- OU-WB Institute for Stem Cell and Regenerative Medicine, Rochester, Michigan
- Department of Biological Sciences, Oakland University, Rochester, Michigan
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20
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Clinical trials of intervertebral disc regeneration: current status and future developments. INTERNATIONAL ORTHOPAEDICS 2018; 43:1003-1010. [DOI: 10.1007/s00264-018-4245-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 12/20/2022]
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21
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Shaw KA, Parada SA, Gloystein DM, Devine JG. The Science and Clinical Applications of Placental Tissues in Spine Surgery. Global Spine J 2018; 8:629-637. [PMID: 30202718 PMCID: PMC6125928 DOI: 10.1177/2192568217747573] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
STUDY DESIGN Narrative literature review. OBJECTIVES Placental tissue, amniotic/chorionic membrane, and umbilical cord have seen a recent expansion in their clinical application in various fields of surgery. It is important for practicing surgeons to know the underlying science, especially as it relates to spine surgery, to understand the rationale and clinical indication, if any, for their usage. METHODS A literature search was performed using PubMed and MEDLINE databases to identify studies reporting the application of placental tissues as it relates to the practicing spine surgeon. Four areas of interest were identified and a comprehensive review was performed of available literature. RESULTS Clinical application of placental tissue holds promise with regard to treatment of intervertebral disc pathology, preventing epidural fibrosis, spinal dysraphism closure, and spinal cord injury; however, there is an overall paucity of high-quality evidence. As such, evidence-based guidelines for its clinical application are currently unavailable. CONCLUSIONS There is no high-level clinical evidence to support the application of placental tissue for spinal surgery, although it does hold promise for several areas of interest for the practicing spine surgeon. High-quality research is needed to define the clinical effectiveness and indications of placental tissue as it relates to spine surgery.
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Affiliation(s)
- K. Aaron Shaw
- Dwight D. Eisenhower Army Medical Center, Fort Gordon, GA, USA,K. Aaron Shaw, Department of Orthopaedic Surgery, Dwight D. Eisenhower Army Medical Center, 300 East Hospital Road, Fort Gordon, GA 30905, USA.
| | | | | | - John G. Devine
- Medical College of Georgia, Augusta University, Augusta, GA, USA
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