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1
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Xing WB, Wu ST, Wang XX, Li FY, Wang RX, He JH, Fu J, He Y. Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications. World J Stem Cells 2023; 15:960-978. [PMID: 37970238 PMCID: PMC10631371 DOI: 10.4252/wjsc.v15.i10.960] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 10/26/2023] Open
Abstract
Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
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Affiliation(s)
- Wen-Bo Xing
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Shu-Ting Wu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Xin-Xin Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Fen-Yao Li
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ruo-Xuan Wang
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ji-Hui He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Jiao Fu
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Yan He
- Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- First Clinical College, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Stomatology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430000, Hubei Province, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, Hubei Province, China.
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Hörner SJ, Couturier N, Gueiber DC, Hafner M, Rudolf R. Development and In Vitro Differentiation of Schwann Cells. Cells 2022; 11:3753. [PMID: 36497014 PMCID: PMC9739763 DOI: 10.3390/cells11233753] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/16/2022] [Accepted: 11/22/2022] [Indexed: 11/25/2022] Open
Abstract
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human Schwann cells are challenging to obtain in large quantities, in vitro differentiation from other cell types presents an alternative. Here, we first review the current knowledge on the developmental signaling mechanisms that determine neural crest and Schwann cell differentiation in vivo. Next, an overview of studies on the in vitro differentiation of Schwann cells from multipotent stem cell sources is provided. The molecules frequently used in those protocols and their involvement in the relevant signaling pathways are put into context and discussed. Focusing on hiPSC- and hESC-based studies, different protocols are described and compared, regarding cell sources, differentiation methods, characterization of cells, and protocol efficiency. A brief insight into developments regarding the culture and differentiation of Schwann cells in 3D is given. In summary, this contribution provides an overview of the current resources and methods for the differentiation of Schwann cells, it supports the comparison and refinement of protocols and aids the choice of suitable methods for specific applications.
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Affiliation(s)
- Sarah Janice Hörner
- Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany
- Center for Mass Spectrometry and Optical Spectroscopy, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
| | - Nathalie Couturier
- Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany
- Center for Mass Spectrometry and Optical Spectroscopy, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
| | - Daniele Caroline Gueiber
- Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany
- Center for Mass Spectrometry and Optical Spectroscopy, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Department of Electronics Engineering, Federal University of Technology Paraná, Ponta Grossa 84017-220, Brazil
| | - Mathias Hafner
- Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Institute of Medical Technology, Heidelberg University and Mannheim University of Applied Sciences, 69117 Heidelberg, Germany
| | - Rüdiger Rudolf
- Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Interdisciplinary Center for Neurosciences, Heidelberg University, 69120 Heidelberg, Germany
- Center for Mass Spectrometry and Optical Spectroscopy, Mannheim University of Applied Sciences, 68163 Mannheim, Germany
- Institute of Medical Technology, Heidelberg University and Mannheim University of Applied Sciences, 69117 Heidelberg, Germany
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3
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Yang L, Shen XM, Wang ZF, Li K, Wang W. The Notch signalling pathway and miRNA regulation play important roles in the differentiation of Schwann cells from adipose-derived stem cells. J Transl Med 2022; 102:320-328. [PMID: 34795395 DOI: 10.1038/s41374-021-00687-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 11/08/2022] Open
Abstract
An exploration of the underlying mechanisms is necessary to improve nerve myelin-forming cell Schwann cell (SC) differentiation from adipose-derived stem cells (ADSCs). Primary rat ADSCs were isolated and characterised for cell surface markers using flow cytometry analysis. After treatment with a mixture of glial growth factors, ADSCs were induced to differentiate and subsequently identified by immunofluorescence staining and western blotting. A miRNA microarray analysis was performed to explore the genes and signalling pathways regulating ADSC differentiation into SCs. ELISAs were conducted to measure the expression of neurotrophic factors and changes in the level of nerve cell adhesion factor. Dual luciferase reporter assays and RIP assays were performed to explore the potential mechanism of miR-21-5p in ADSC differentiation. The isolated ADSCs were positive for CD29 and CD44 but negative for CD49. After induction with specific cytokines, the differentiated ADSCs presented a spindle-like morphology similar to SCs and expressed S100. RNA-sequencing analyses revealed that 9821 mRNAs of protein-coding genes and 175 miRNAs were differentially expressed in differentiated SC-like cells compared to primary cultures of ADSCs. KEGG and Gene Ontology analyses revealed that the involvement of the Notch signalling pathway and miRNA negative regulation may be associated with the differentiation of ADSCs into SCs. Treatment with a Notch inhibitor promoted the differentiation of ADSCs. Furthermore, mechanistic studies showed that Jag1 bound to miR-21-5p and upregulated its target gene Jag1, thus affecting ADSC differentiation. These results revealed the mechanism underlying the important roles of miRNAs and the Notch signalling pathway in the differentiation of SCs from ADSCs, enabling potential therapeutic applications of ADSCs in peripheral nerve regeneration in the future.
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Affiliation(s)
- Liang Yang
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, Changsha, 410078, P.R. China
| | - Xiang-Min Shen
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011, P.R. China
| | - Zhi-Fei Wang
- Department of Neurosurgery, The Third Xiangya Hospital of Central South University, Changsha, 410078, P.R. China
| | - Ke Li
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011, P.R. China
| | - Wei Wang
- Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011, P.R. China.
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Mouse Neural Stem Cell Differentiation and Human Adipose Mesenchymal Stem Cell Transdifferentiation Into Neuron- and Oligodendrocyte-like Cells With Myelination Potential. Stem Cell Rev Rep 2021; 18:732-751. [PMID: 34780018 DOI: 10.1007/s12015-021-10218-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2021] [Indexed: 01/09/2023]
Abstract
Stem cell therapy is an interesting approach for neural repair, once it can improve and increase processes, like angiogenesis, neurogenesis, and synaptic plasticity. In this regard, adult neural stem cells (NSC) are studied for their mechanisms of proliferation, differentiation and functionality in neural repair. Here, we describe novel neural differentiation methods. NSC from adult mouse brains and human adipose-derived stem cells (hADSC) were isolated and characterized regarding their neural differentiation potential based on neural marker expression profiles. For both cell types, their capabilities of differentiating into neuron-, astrocyte- and oligodendrocytes-like cells (NLC, ALC and OLC, respectively) were analyzed. Our methodologies were capable of producing NLC, ALC and OLC from adult murine and human transdifferentiated NSC. NSC showed augmented gene expression of NES, TUJ1, GFAP and PDGFRA/Cnp. Following differentiation induction into NLC, OLC or ALC, specific neural phenotypes were obtained expressing MAP2, GalC/O4 or GFAP with compatible morphologies, respectively. Accordingly, immunostaining for nestin+ in NSC, GFAP+ in astrocytes and GalC/O4+ in oligodendrocytes was detected. Co-cultured NLC and OLC showed excitability in 81.3% of cells and 23.5% of neuron/oligodendrocyte marker expression overlap indicating occurrence of in vitro myelination. We show here that hADSC can be transdifferentiated into NSC and distinct neural phenotypes with the occurrence of neuron myelination in vitro, providing novel strategies for CNS regeneration therapy. Superior Part: Schematic organization of obtaining and generating hNSC from hADSC and differentiation processes and phenotypic expression of neuron, astrocyte and oligodendrocyte markers (MAP2, GFAP and O4, respectively) and stem cell marker (NES) of differentiating hNSC 14 days after induction. The nuclear staining in blue corresponds to DAPI. bar = 100 μm. Inferior part: Neural phenotype fates in diverse differentiation media. NES: nestin; GFAP: Glial fibrillary acidic protein. MAP2: Microtubule-associated protein 2. TUJ1: β-III tubulin. PDGFRA: PDGF receptor alpha. Two-way ANOVA with Bonferroni post-test with n = 3. * p < 0.05 and ** p < 0.01: (NSCiM1 NSC induction medium 1) vs differentiation media.
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Huang Z, Powell R, Phillips JB, Haastert-Talini K. Perspective on Schwann Cells Derived from Induced Pluripotent Stem Cells in Peripheral Nerve Tissue Engineering. Cells 2020; 9:E2497. [PMID: 33213068 PMCID: PMC7698557 DOI: 10.3390/cells9112497] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 11/13/2020] [Accepted: 11/16/2020] [Indexed: 02/06/2023] Open
Abstract
Schwann cells play a crucial role in successful peripheral nerve repair and regeneration by supporting both axonal growth and myelination. Schwann cells are therefore a feasible option for cell therapy treatment of peripheral nerve injury. However, sourcing human Schwann cells at quantities required for development beyond research is challenging. Due to their availability, rapid in vitro expansion, survival, and integration within the host tissue, stem cells have attracted considerable attention as candidate cell therapies. Among them, induced pluripotent stem cells (iPSCs) with the associated prospects for personalized treatment are a promising therapy to take the leap from bench to bedside. In this critical review, we firstly focus on the current knowledge of the Schwann cell phenotype in regard to peripheral nerve injury, including crosstalk with the immune system during peripheral nerve regeneration. Then, we review iPSC to Schwann cell derivation protocols and the results from recent in vitro and in vivo studies. We finally conclude with some prospects for the use of iPSCs in clinical settings.
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Affiliation(s)
- Zhong Huang
- Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30623 Hannover, Germany;
- Center for Systems Neuroscience (ZSN) Hannover, 30559 Hannover, Germany
| | - Rebecca Powell
- Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK;
- UCL Centre for Nerve Engineering, University College London, London WC1E 6BT, UK
| | - James B. Phillips
- Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK;
- UCL Centre for Nerve Engineering, University College London, London WC1E 6BT, UK
| | - Kirsten Haastert-Talini
- Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30623 Hannover, Germany;
- Center for Systems Neuroscience (ZSN) Hannover, 30559 Hannover, Germany
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6
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Pisciotta A, Bertoni L, Vallarola A, Bertani G, Mecugni D, Carnevale G. Neural crest derived stem cells from dental pulp and tooth-associated stem cells for peripheral nerve regeneration. Neural Regen Res 2020; 15:373-381. [PMID: 31571644 PMCID: PMC6921350 DOI: 10.4103/1673-5374.266043] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 05/11/2019] [Indexed: 12/15/2022] Open
Abstract
The peripheral nerve injuries, representing some of the most common types of traumatic lesions affecting the nervous system, are highly invalidating for the patients besides being a huge social burden. Although peripheral nervous system owns a higher regenerative capacity than does central nervous system, mostly depending on Schwann cells intervention in injury repair, several factors determine the extent of functional outcome after healing. Based on the injury type, different therapeutic approaches have been investigated so far. Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries, however these approaches own limitations, such as scarce donor nerve availability and donor site morbidity. Cell based therapies might provide a suitable tool for peripheral nerve regeneration, in fact, the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade. Dental pulp is a promising cell source for regenerative medicine, because of the ease of isolation procedures, stem cell proliferation and multipotency abilities, which are due to the embryological origin from neural crest. In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models, highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.
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Affiliation(s)
- Alessandra Pisciotta
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Laura Bertoni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Antonio Vallarola
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Bertani
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniela Mecugni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
- Azienda USL - Institute and Health Care (IRCCS) di Reggio Emilia, Reggio Emilia, Italy
| | - Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
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7
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George S, Hamblin MR, Abrahamse H. Differentiation of Mesenchymal Stem Cells to Neuroglia: in the Context of Cell Signalling. Stem Cell Rev Rep 2019; 15:814-826. [PMID: 31515658 PMCID: PMC6925073 DOI: 10.1007/s12015-019-09917-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The promise of engineering specific cell types from stem cells and rebuilding damaged or diseased tissues has fascinated stem cell researchers and clinicians over last few decades. Mesenchymal Stem Cells (MSCs) have the potential to differentiate into non-mesodermal cells, particularly neural-lineage, consisting of neurons and glia. These multipotent adult stem cells can be used for implementing clinical trials in neural repair. Ongoing research identifies several molecular mechanisms involved in the speciation of neuroglia, which are tightly regulated and interconnected by various components of cell signalling machinery. Growing MSCs with multiple inducers in culture media will initiate changes on intricately interlinked cell signalling pathways and processes. Net result of these signal flow on cellular architecture is also dependent on the type of ligands and stem cells investigated in vitro. However, our understanding about this dynamic signalling machinery is limited and confounding, especially with spheroid structures, neurospheres and organoids. Therefore, the results for differentiating neurons and glia in vitro have been inconclusive, so far. Added to this complication, we have no convincing evidence about the electrical conductivity and functionality status generated in differentiating neurons and glia. This review has taken a step forward to tailor the information on differentiating neuroglia with the common methodologies, in practice.
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Affiliation(s)
- Sajan George
- Laser Research Centre, University of Johannesburg, P.O. Box 17011, Doornfontein, 2028, South Africa
| | - Michael R Hamblin
- Laser Research Centre, University of Johannesburg, P.O. Box 17011, Doornfontein, 2028, South Africa
- Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA
- Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA
| | - Heidi Abrahamse
- Laser Research Centre, University of Johannesburg, P.O. Box 17011, Doornfontein, 2028, South Africa.
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Ramli K, Aminath Gasim I, Ahmad AA, Hassan S, Law ZK, Tan GC, Baharuddin A, Naicker AS, Htwe O, Mohammed Haflah NH, B H Idrus R, Abdullah S, Ng MH. Human bone marrow-derived MSCs spontaneously express specific Schwann cell markers. Cell Biol Int 2019; 43:233-252. [PMID: 30362196 DOI: 10.1002/cbin.11067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 10/07/2018] [Indexed: 12/15/2022]
Abstract
In peripheral nerve injuries, Schwann cells (SC) play pivotal roles in regenerating damaged nerve. However, the use of SC in clinical cell-based therapy is hampered due to its limited availability. In this study, we aim to evaluate the effectiveness of using an established induction protocol for human bone marrow derived-MSC (hBM-MSCs) transdifferentiation into a SC lineage. A relatively homogenous culture of hBM-MSCs was first established after serial passaging (P3), with profiles conforming to the minimal criteria set by International Society for Cellular Therapy (ISCT). The cultures (n = 3) were then subjected to a series of induction media containing β-mercaptoethanol, retinoic acid, and growth factors. Quantitative RT-PCR, flow cytometry, and immunocytochemistry analyses were performed to quantify the expression of specific SC markers, that is, S100, GFAP, MPZ and p75 NGFR, in both undifferentiated and transdifferentiated hBM-MSCs. Based on these analyses, all markers were expressed in undifferentiated hBM-MSCs and MPZ expression (mRNA transcripts) was consistently detected before and after transdifferentiation across all samples. There was upregulation at the transcript level of more than twofolds for NGF, MPB, GDNF, p75 NGFR post-transdifferentiation. This study highlights the existence of spontaneous expression of specific SC markers in cultured hBM-MSCs, inter-donor variability and that MSC transdifferentiation is a heterogenous process. These findings strongly oppose the use of a single marker to indicate SC fate. The heterogenous nature of MSC may influence the efficiency of SC transdifferentiation protocols. Therefore, there is an urgent need to re-define the MSC subpopulations and revise the minimal criteria for MSC identification.
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Affiliation(s)
- Khairunnisa Ramli
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Ifasha Aminath Gasim
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Amir Adham Ahmad
- Department of Orthopaedics, School of Medicine, International Medical University, Negeri Sembilan, Malaysia
| | - Shariful Hassan
- Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Zhe Kang Law
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Geok Chin Tan
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Azmi Baharuddin
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Amaramalar Selvi Naicker
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ohnmar Htwe
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nor Hazla Mohammed Haflah
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ruszymah B H Idrus
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Shalimar Abdullah
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Min Hwei Ng
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
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Luo L, Hu DH, Yin JQ, Xu RX. Molecular Mechanisms of Transdifferentiation of Adipose-Derived Stem Cells into Neural Cells: Current Status and Perspectives. Stem Cells Int 2018; 2018:5630802. [PMID: 30302094 PMCID: PMC6158979 DOI: 10.1155/2018/5630802] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 07/12/2018] [Accepted: 07/19/2018] [Indexed: 12/19/2022] Open
Abstract
Neurological diseases can severely compromise both physical and psychological health. Recently, adult mesenchymal stem cell- (MSC-) based cell transplantation has become a potential therapeutic strategy. However, most studies related to the transdifferentiation of MSCs into neural cells have had disappointing outcomes. Better understanding of the mechanisms underlying MSC transdifferentiation is necessary to make adult stem cells more applicable to treating neurological diseases. Several studies have focused on adipose-derived stromal/stem cell (ADSC) transdifferentiation. The purpose of this review is to outline the molecular characterization of ADSCs, to describe the methods for inducing ADSC transdifferentiation, and to examine factors influencing transdifferentiation, including transcription factors, epigenetics, and signaling pathways. Exploring and understanding the mechanisms are a precondition for developing and applying novel cell therapies.
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Affiliation(s)
- Liang Luo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi 710032, China
- Stem Cell Research Center, Neurosurgery Institute of PLA Army, Beijing 100700, China
- Bayi Brain Hospital, General Hospital of PLA Army, Beijing 100700, China
| | - Da-Hai Hu
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi 710032, China
| | - James Q. Yin
- Stem Cell Research Center, Neurosurgery Institute of PLA Army, Beijing 100700, China
- Bayi Brain Hospital, General Hospital of PLA Army, Beijing 100700, China
| | - Ru-Xiang Xu
- Stem Cell Research Center, Neurosurgery Institute of PLA Army, Beijing 100700, China
- Bayi Brain Hospital, General Hospital of PLA Army, Beijing 100700, China
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10
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George S, Hamblin MR, Abrahamse H. Current and Future Trends in Adipose Stem Cell Differentiation into Neuroglia. Photomed Laser Surg 2018; 36:230-240. [PMID: 29570423 DOI: 10.1089/pho.2017.4411] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Neurological diseases and disorders pose a challenge for treatment and rehabilitation due to the limited capacity of the nervous system to repair itself. Adipose stem cells (ASCs) are more pliable than any adult stem cells and are capable of differentiating into non-mesodermal tissues, including neurons. Transdifferentiating ASCs to specific neuronal lineage cells enables us to deliver the right type of cells required for a replacement therapy into the nervous system. METHODS Several methodologies are being explored and tested to differentiate ASCs to functional neurons and glia with cellular factors and chemical compounds. However, none of these processes and prototypes has been wholly successful in changing the cellular structure and functional status of ASCs to become identical to neuroglial cells. In addition, successful integration and functional competence of these cells for use in clinical applications remain problematic. Photobiomodulation or low-level laser irradiation has been successfully applied to not only improve ASC viability and proliferation but has also shown promise as a possible enhancer of ASC differentiation. CONCLUSIONS Studies have shown that photobiomodulation improves the use of stem cell transplantation for neurological applications. This review investigates current neuro-differentiation inducers and suitable methodologies, including photobiomodulation, utilizing ASCs for induction of differentiation into neuronal lineages.
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Affiliation(s)
- Sajan George
- 1 Laser Research Centre, Faculty of Health Sciences, University of Johannesburg , Doornfontein, South Africa
| | - Michael R Hamblin
- 2 Wellman Centre for Photomedicine, Massachusetts General Hospital , Boston, Massachusetts.,3 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.,4 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts
| | - Heidi Abrahamse
- 1 Laser Research Centre, Faculty of Health Sciences, University of Johannesburg , Doornfontein, South Africa
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11
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Ghasemi N. Transdifferentiation of human adipose-derived mesenchymal stem cells into oligodendrocyte progenitor cells. IRANIAN JOURNAL OF NEUROLOGY 2018; 17:24-30. [PMID: 30186556 PMCID: PMC6121205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Background: Stem cell-based therapy is a new method for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Human adipose-derived stem cells (hADSCs) are a kind of adult stem cells which have a higher frequency in the fat tissue and have the ability to differentiate into other cell types outside their lineage. Due to some serious adverse events of cell-based therapy such as tumorigenic potential, the aim of this study was to evaluate of hADSCs differentiation into oligodendrocytes as a valuable way for future cell transplantation. Methods: hADSC were isolated from lipoaspirate samples of human abdominal fat. After hADSC characterization via flow cytometry, the cells were induced to oligodendrocytes using a special differentiation medium. Finally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), immunocytochemistry, and real-time polymerase chain reaction (RT-PCR) techniques were used for the evaluation of differentiated cells. Results: Flow cytometry indicated that hADSCs were CD105- and CD49-positive, but were negative for CD31 and CD45 markers. In addition, immunocytochemistry analysis revealed that a high percent of differentiated cells expressed oligodendrocyte progenitor cells markers [A2B5 and oligodendrocyte transcription factor (Olig2)] which were significantly higher than myelin basic protein (MBP) which is mature oligodendrocytes marker. Moreover, a very low percentage of differentiated cells expressed glial fibrillary acidic protein (GFAP) marker. Finally, real-time reverse transcription PCR analysis confirmed the results of immunocytochemistry. Conclusion: Since hADSCs have the potential to differentiate into multi-lineage cells and due to their additional characteristics such as immunomodulatory and neuroprotective properties, it seems that these cells may be an ideal cell source for oligodendrocytes differentiation.
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12
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Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/ β-Catenin Signaling Pathway. BIOMED RESEARCH INTERNATIONAL 2017; 2017:4210867. [PMID: 29085837 PMCID: PMC5632471 DOI: 10.1155/2017/4210867] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 06/05/2017] [Accepted: 08/06/2017] [Indexed: 12/17/2022]
Abstract
Adipose tissue-derived stromal cells (ADSCs) are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract) on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9). Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.
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Bierlein De la Rosa M, Sharma AD, Mallapragada SK, Sakaguchi DS. Transdifferentiation of brain-derived neurotrophic factor (BDNF)-secreting mesenchymal stem cells significantly enhance BDNF secretion and Schwann cell marker proteins. J Biosci Bioeng 2017; 124:572-582. [PMID: 28694020 DOI: 10.1016/j.jbiosc.2017.05.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 05/09/2017] [Accepted: 05/23/2017] [Indexed: 01/03/2023]
Abstract
The use of genetically modified mesenchymal stem cells (MSCs) is a rapidly growing area of research targeting delivery of therapeutic factors for neuro-repair. Cells can be programmed to hypersecrete various growth/trophic factors such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) to promote regenerative neurite outgrowth. In addition to genetic modifications, MSCs can be subjected to transdifferentiation protocols to generate neural cell types to physically and biologically support nerve regeneration. In this study, we have taken a novel approach by combining these two unique strategies and evaluated the impact of transdifferentiating genetically modified MSCs into a Schwann cell-like phenotype. After 8 days in transdifferentiation media, approximately 30-50% of transdifferentiated BDNF-secreting cells immunolabeled for Schwann cell markers such as S100β, S100, and p75NTR. An enhancement was observed 20 days after inducing transdifferentiation with minimal decreases in expression levels. BDNF production was quantified by ELISA, and its biological activity tested via the PC12-TrkB cell assay. Importantly, the bioactivity of secreted BDNF was verified by the increased neurite outgrowth of PC12-TrkB cells. These findings demonstrate that not only is BDNF actively secreted by the transdifferentiated BDNF-MSCs, but also that it has the capacity to promote neurite sprouting and regeneration. Given the fact that BDNF production remained stable for over 20 days, we believe that these cells have the capacity to produce sustainable, effective, BDNF concentrations over prolonged time periods and should be tested within an in vivo system for future experiments.
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Affiliation(s)
- Metzere Bierlein De la Rosa
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
| | - Anup D Sharma
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA
| | - Surya K Mallapragada
- Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA
| | - Donald S Sakaguchi
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA; Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA; Neuroscience Program, Iowa State University, Ames, IA 50011, USA.
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14
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Salehi H, Amirpour N, Niapour A, Razavi S. An Overview of Neural Differentiation Potential of Human Adipose Derived Stem Cells. Stem Cell Rev Rep 2016; 12:26-41. [PMID: 26490462 DOI: 10.1007/s12015-015-9631-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
There is wide interest in application of adult stem cells due to easy to obtain with a minimal patient discomfort, capable of producing cell numbers in large quantities and their immunocompatible properties without restriction by ethical concerns. Among these stem cells, multipotent mesenchymal stem cells (MSCs) from human adipose tissue are considered as an ideal source for various regenerative medicine. In spite of mesodermal origin of human adipose-derived stem cells (hADSCs), these cells have differentiation potential toward mesodermal and non-mesodermal lineages. Up to now, several studies have shown that hADSCs can undergo transdifferentiation and produce cells outside of their lineage, especially into neural cells when they are transferred to a specific cell environment. The purpose of this literature review is to provide an overview of the existing state of knowledge of the differentiation potential of hADSCs, specifically their ability to give rise to neuronal cells. The following review discusses different protocols considered for differentiation of hADSCs to neural cells, the neural markers that are used in each procedure and possible mechanisms that are involved in this differentiation.
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15
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Shahbazi-Gahrouei D, Hashemi-Beni B, Ahmadi Z. Effects of RF-EMF Exposure from GSM Mobile Phones on Proliferation Rate of Human Adipose-derived Stem Cells: An In-vitro Study. J Biomed Phys Eng 2016; 6:243-252. [PMID: 28144594 PMCID: PMC5219575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Accepted: 07/12/2015] [Indexed: 06/06/2023]
Abstract
BACKGROUND As the use of mobile phones is increasing, public concern about the harmful effects of radiation emitted by these devices is also growing. In addition, protection questions and biological effects are among growing concerns which have remained largely unanswered. Stem cells are useful models to assess the effects of radiofrequency electromagnetic fields (RF-EMF) on other cell lines. Stem cells are undifferentiated biological cells that can differentiate into specialized cells. Adipose tissue represents an abundant and accessible source of adult stem cells. The aim of this study is to investigate the effects of GSM 900 MHz on growth and proliferation of mesenchymal stem cells derived from adipose tissue within the specific distance and intensity. MATERIALS AND METHODS ADSCs were exposed to GSM mobile phones 900 MHz with intensity of 354.6 µW/cm2 square waves (217 Hz pulse frequency, 50% duty cycle), during different exposure times ranging from 6 to 21 min/day for 5 days at 20 cm distance from the antenna. MTT assay was used to determine the growth and metabolism of cells and trypan blue test was also done for cell viability. Statistical analyses were carried out using analysis of one way ANOVA. P<0.05 was considered to be statistically significant. RESULTS The proliferation rates of human ADSCs in all exposure groups were significantly lower than control groups (P<0.05) except in the group of 6 minutes/day which did not show any significant difference with control groups. CONCLUSION The results show that 900 MHz RF signal radiation from antenna can reduce cell viability and proliferation rates of human ADSCs regarding the duration of exposure.
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Affiliation(s)
- D Shahbazi-Gahrouei
- Professor of Medical Physics, Dept. of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - B Hashemi-Beni
- Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Z Ahmadi
- MSc of Medical Physics, Dept. of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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16
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Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration. Int J Mol Sci 2016; 17:ijms17111867. [PMID: 27834852 PMCID: PMC5133867 DOI: 10.3390/ijms17111867] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 11/02/2016] [Accepted: 11/04/2016] [Indexed: 12/30/2022] Open
Abstract
Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.
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17
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Effect of Laminin on Neurotrophic Factors Expression in Schwann-Like Cells Induced from Human Adipose-Derived Stem Cells In Vitro. J Mol Neurosci 2016; 60:465-473. [PMID: 27501706 DOI: 10.1007/s12031-016-0808-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 07/28/2016] [Indexed: 12/30/2022]
Abstract
The Schwann-like cells can be considered as promising in stem cell therapies, at least in experimental models. Human adipose-derived stem cells (ADSCs) are induced into Schwann-like cells (SC-like cells) and are cultured on either a plastic surface or laminin-coated plates. The findings here reveal that laminin is a critical component in extracellular matrix (ECM) of SC-like cells at in vitro. The survival rate of SC-like cells on a laminin matrix are measured through MTT assay and it is found that this rate is significantly higher than that of the cells grown on a plastic surface (P < 0.05). Schwann cell markers and the myelinogenic ability of SC-like cells at the presence versus absence of laminin are assessed through immunocytochemistry. The analysis of GFAP/S100β and S100β/MBP markers indicate that laminin can increase the differentiated rate and myelinogenic potential of SC-like cells. The expression levels of SCs markers, myelin basic proteins (MBP), and neurotrophic factors in two conditions are analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The findings here demonstrated that gene expression of SCs markers, MBP, and brain-derived neurotrophic factors (BDNF) increase significantly on laminin compared to plastic surface (P < 0.01). In contrast, the nerve growth factor (NGF) expression is downregulated significantly on laminin-coated plates (P < 0.05). The obtained data suggest that production of neurotrophic factors in SC-like cell in presence of laminin can induce appropriate microenvironment for nerve repair in neurodegenerative diseases.
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18
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Liu Y, Zhang Z, Zhang C, Deng W, Lv Q, Chen X, Huang T, Pan L. Adipose-derived stem cells undergo spontaneous osteogenic differentiation in vitro when passaged serially or seeded at low density. Biotech Histochem 2016; 91:369-76. [PMID: 27149413 DOI: 10.1080/10520295.2016.1175026] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Adipose-derived stem cells (ADSCs) are a convenient source of cells for regenerating tissue. Widespread application of ADSCs requires that they propagate efficiently and differentiate in vitro. We investigated the differentiation potential of ADSCs during long-term expansion in vitro and when the cells were seeded at low density. ADSCs were isolated from the inguinal fat pads of 3-week-old male rats, then cultured serially for 12 passages; some ADSCs at passage 3 were seeded at low density. The differentiation potential of ADSCs from passage 3 to passage 12 was assessed by their capacity for adipogenesis and osteogenesis while cultured in specific induction media. Spontaneous osteogenesis of ADSCs at passage 12 and of ADSCs that were seeded at low density was detected by western blotting, alizarin red S staining and measurement of alkaline phosphatase (ALP) activity. We found that with increasing passage number, the adipogenic potential of ADSCs decreased and osteogenic differentiation increased. Alizarin red S staining, bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (Runx2) expressions, and ALP activity demonstrated that both ADSCs at passage 12 and those that were seeded at low density differentiated into osteoblasts without additional induction factors.
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Affiliation(s)
- Y Liu
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - Z Zhang
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - C Zhang
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - W Deng
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - Q Lv
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - X Chen
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - T Huang
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
| | - L Pan
- a College of Animal Science and Technology, Henan University of Science and Technology , Luoyang , P. R. China
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Ribeiro TB, Duarte ASS, Longhini ALF, Pradella F, Farias AS, Luzo ACM, Oliveira ALR, Olalla Saad ST. Neuroprotection and immunomodulation by xenografted human mesenchymal stem cells following spinal cord ventral root avulsion. Sci Rep 2015; 5:16167. [PMID: 26548646 PMCID: PMC4637826 DOI: 10.1038/srep16167] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 10/07/2015] [Indexed: 12/21/2022] Open
Abstract
The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM-MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 × 10(5) AT-MSCs via the lateral funiculus. Two weeks after cell administration, the animals were sacrificed and the moto neurons, T lymphocytes and cell defense nervous system were analyzed. An increased neuronal survival and partial preservation of synaptophysin-positive nerve terminals, related to GDNF and BDNF expression of AT-MSCs, and reduction of pro-inflammatory reaction were observed. In conclusion, AT-MSCs prevent second phase neuronal injury, since they suppressed lymphocyte, astroglia and microglia effects, which finally contributed to rat motor-neuron survival and synaptic stability of the lesioned motor-neuron. Moreover, the survival of the injected AT- MSCs lasted for at least 14 days. These results indicate that neuronal survival after lesion, followed by mesenchymal stem cell (MSC) administration, might occur through cytokine release and immunomodulation, thus suggesting that AT-MSCs are promising cells for the therapy of neuronal lesions.
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Affiliation(s)
- Thiago B. Ribeiro
- Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil
| | - Adriana S. S. Duarte
- Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil
| | - Ana Leda F. Longhini
- Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil
- Neuroimmunomodulation Group, Dept. Genetics, Evolution and Bioagents, University of Campinas, Campinas, Brazil
| | - Fernando Pradella
- Neuroimmunomodulation Group, Dept. Genetics, Evolution and Bioagents, University of Campinas, Campinas, Brazil
| | - Alessandro S. Farias
- Neuroimmunomodulation Group, Dept. Genetics, Evolution and Bioagents, University of Campinas, Campinas, Brazil
| | - Angela C. M. Luzo
- Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil
| | - Alexandre L. R. Oliveira
- Dept. of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Sara Teresinha Olalla Saad
- Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil
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20
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Wakao S, Matsuse D, Dezawa M. Mesenchymal stem cells as a source of Schwann cells: their anticipated use in peripheral nerve regeneration. Cells Tissues Organs 2015; 200:31-41. [PMID: 25765009 DOI: 10.1159/000368188] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2014] [Indexed: 11/19/2022] Open
Abstract
Schwann cells form myelin, sustain axons and provide the microenvironment for nerve fibers, thereby playing a key role in the peripheral nervous system (PNS). Schwann cells also provide support for the damaged PNS by producing factors that strongly promote axonal regrowth and contribute to remyelination, which is crucial for the recovery of neural function. These advantages are not confined to the PNS and also apply to the central nervous system. Many diseases, including peripheral nerve injury, neuropathy, multiple sclerosis and spinal cord injury, are targets for Schwann cell therapy. The collection of Schwann cells, however, causes new damage to other peripheral nerve segments. Furthermore, the doubling time of Schwann cells is not very fast, and thus adequate amounts of Schwann cells for clinical use cannot be collected within a reasonable amount of time. Mesenchymal stem cells, which are highly proliferative, are easily accessible from various types of mesenchymal tissues, such as the bone marrow, umbilical cord and fat tissue. Because these cells have the ability to cross oligolineage boundaries between mesodermal to ectodermal lineages, they are capable of differentiating into Schwann cells with step-by-step cytokine stimulation. In this review, we summarize the properties of mesenchymal stem cell-derived Schwann cells, which are comparable to authentic Schwann cells, and discuss future perspectives.
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Affiliation(s)
- Shohei Wakao
- Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan
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21
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Generation of neurospheres from human adipose-derived stem cells. BIOMED RESEARCH INTERNATIONAL 2015; 2015:743714. [PMID: 25815334 PMCID: PMC4357140 DOI: 10.1155/2015/743714] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2014] [Revised: 01/24/2015] [Accepted: 02/10/2015] [Indexed: 01/29/2023]
Abstract
Transplantation of neural stem cells (NSCs) to treat neurodegenerative disease shows promise; however, the clinical application of NSCs is limited by the invasive procurement and ethical concerns. Adipose-derived stem cells (ADSCs) are a source of multipotent stem cells that can self-renew and differentiate into various kinds of cells; this study intends to generate neurospheres from human ADSCs by culturing ADSCs on uncoated culture flasks in serum-free neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF); the ADSCs-derived neurospheres were terminally differentiated after growth factor withdrawal. Expression of Nestin, NeuN, MAP2, and GFAP in ADSCs and terminally differentiated neurospheres was shown by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry; cell proliferation in neurospheres was evaluated by cell cycle analyses, immunostaining, and flow cytometry. These data strongly support the conclusion that human ADSCs can successfully differentiate into neurospheres efficiently on uncoated culture flasks, which present similar molecular marker pattern and proliferative ability with NSCs derived from embryonic and adult brain tissues. Therefore, human ADSCs may be an ideal alternative source of stem cells for the treatment of neurodegenerative diseases.
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22
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Razavi S, Zarkesh-Esfahani H, Morshed M, Vaezifar S, Karbasi S, Golozar MA. Nanobiocomposite of poly(lactide-co-glycolide)/chitosan electrospun scaffold can promote proliferation and transdifferentiation of Schwann-like cells from human adipose-derived stem cells. J Biomed Mater Res A 2015; 103:2628-34. [PMID: 25614290 DOI: 10.1002/jbm.a.35398] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2014] [Revised: 12/15/2014] [Accepted: 01/04/2015] [Indexed: 12/20/2022]
Abstract
The transdifferentiation of human adipose-derived stem cells (ADSCs) into Schwann-like cells on biocomposite scaffolds may be a critical issue in nerve regeneration medicine. In this study, tissue-engineered scaffold with chitosan (CS) nanopowders and poly(lactide-co-glycolide) (PLGA) was investigated for its potential Schwann cells (SCs) transdifferentiation. The differentiation of human ADSCs into S-like cells was induced with different CS content and direction of nanofibers on PLGA/CS scaffolds. Cell morphology and proliferation of differentiated cells were investigated by scanning electron microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay respectively. For assessment efficiency of transdifferentiation, the expression of SC markers (glial fibrillary acidic protein and S100), and myelinogenic marker (myelin basic protein) was investigated in different nanochitosan content and direction of nanofibers scaffolds, using immunocytochemistry technique. The nanochitosan can significantly promote cell proliferation of differentiated cells (p < 0.05). The mean percentage of S-like cells on greater CS content nanofibers scaffold was significantly higher than others (p < 0.05). In addition, the align orientation of nanofibers in scaffolds guided the differentiation of ADSCs toward myelinating S-like cells on the constructs. Overall, we found that high CS content and aligned-orientation of nanofibers in biocomposite scaffold (70/30A) can promote differentiation and myelinogenic capacity of S-like cells induced from human ADSCs.
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Affiliation(s)
- Shahnaz Razavi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81744-176, Iran
| | | | - Mohammad Morshed
- Department of Textile Engineering, Isfahan University of Technology, Isfahan, 84156-83111, Iran
| | - Sedigheh Vaezifar
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81744-176, Iran.,Department of Materials Engineering, Isfahan University of Technology, Isfahan, 84156-83111, Iran
| | - Saeed Karbasi
- Department of Medical Physics and Biomedical Engineering, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 15875-4413, Iran
| | - Mohammad Ali Golozar
- Department of Materials Engineering, Isfahan University of Technology, Isfahan, 84156-83111, Iran
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23
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Ghasemi N. Therapeutic effects of adipose derived mesenchymal stem cells on remyelination process in inflammatory demyelinating diseases. ACTA ACUST UNITED AC 2015. [DOI: 10.7243/2055-091x-2-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Faroni A, Smith RJ, Reid AJ. Adipose derived stem cells and nerve regeneration. Neural Regen Res 2014; 9:1341-6. [PMID: 25221589 PMCID: PMC4160863 DOI: 10.4103/1673-5374.137585] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2014] [Indexed: 12/25/2022] Open
Abstract
Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.
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Affiliation(s)
- Alessandro Faroni
- Blond McIndoe Laboratories, Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Richard Jp Smith
- Blond McIndoe Laboratories, Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Adam J Reid
- Blond McIndoe Laboratories, Institute of Inflammation and Repair, University of Manchester, Manchester, UK ; Department of Plastic Surgery & Burns, University Hospital of South Manchester, Manchester, UK
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Abbaszadeh HA, Tiraihi T, Delshad A, Saghedizadeh M, Taheri T, Kazemi H, Hassoun HK. Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine. Tissue Cell 2014; 46:462-9. [PMID: 25200619 DOI: 10.1016/j.tice.2014.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 07/22/2014] [Accepted: 08/11/2014] [Indexed: 12/31/2022]
Abstract
One of the approaches for treating demyelination diseases is cytotherapy, and adult stem cells are potential sources. In this investigation, we tried to increase the yield of oligodendrocyte-like cells (OLCs) by inducing neural stem cells generated from BMSCs-derived neurospheres, which were used for deriving the neural stem cells (NSCs). The latter were induced into OLCs by heregulin, PDGF-AA, bFGF and triiodothyronine (T3). The BMSCs, NS, NSCs and OLCs were characterized by using immunocytochemistry for fibronectin, CD44, CD90, CD45, Oct-4, O4, Olig2, O1 and MBP markers. PDGF receptor α (PDGFR-α), Olig2 and MOG expression were evaluated by RT-PCR. The BMSCs expressed CD44, CD90, CD106 and Oct-4; the NSCs were immunoreactive to nestin and neurofilament 68. Incubation of the NSCs for 4 days with heregulin, PDGF-AA and bFGF resulted in their induction into oligodendrocyte progenitor-like cells (OPLCs), which immunoreacted to O4, Olig2 and O1, while Olig2 and PDGFR-α were detected by RT-PCR. Replacing heregulin, PDGF-AA and bFGF with T3 for 6 days resulted in repression of O4, O1, Olig2 and PDGFR-α. The OLCs were co-cultured with motoneurons resulted in induction of MOG and MBP, which were expressed in functional OLCs. The latter can be generated from BMSCs-derive NS with high yield.
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Affiliation(s)
- Hojjat-Allah Abbaszadeh
- Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran
| | - Taki Tiraihi
- Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran; Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.
| | | | - Majid Saghedizadeh
- Department of genetics, School of Basic Sciences, Tarbiat Modares University, Tehran, Iran
| | - Taher Taheri
- Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran
| | - Hadi Kazemi
- Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran
| | - Hayder K Hassoun
- Middle Euphrates Neuroscience Center, Kufa University,College of Medicine, Annajaf Al-Ashraf, Iraq
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Transcriptional profiling predicts overwhelming homology of schwann cells, olfactory ensheathing cells, and schwann cell-like glia. Glia 2014; 62:1559-81. [DOI: 10.1002/glia.22700] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 05/15/2014] [Accepted: 05/16/2014] [Indexed: 01/26/2023]
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Stimpfel M, Cerkovnik P, Novakovic S, Maver A, Virant-Klun I. Putative mesenchymal stem cells isolated from adult human ovaries. J Assist Reprod Genet 2014; 31:959-74. [PMID: 24845159 DOI: 10.1007/s10815-014-0254-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 05/08/2014] [Indexed: 12/26/2022] Open
Abstract
PURPOSE The purpose of this study was to show that healthy adult human ovaries can be a source of cells showing typical MSCs characteristics under in vitro conditions. METHODS AND RESULTS The cells, which were isolated from ovarian cortex tissue and named putative ovarian mesenchymal stem cells (PO-MSCs), were compared to bone marrow-derived MSCs (BM-MSCs) and to adult human dermal fibroblasts (HDFs). The results of a gene expression analysis using the Human Mesenchymal Stem Cell RT² Profiler™ PCR Array revealed that PO-MSCs were different than fibroblasts. They expressed most of the analyzed genes as BM-MSCs, although some genes were differentially expressed. However, the heterogeneity of PO-MSCs samples was revealed. The PO-MSCs expressed the characteristic genes related to MSCs, such as CD105, CD44, CD90, M-CAM, CD73 and VCAM1. In addition, the expression of markers CD44, CD90, M-CAM and STRO-1 was confirmed in PO-MSCs using immunocytochemistry. The PO-MSCs showed multipotent character, since they were able to differentiate into the cells of adipogenic, osteogenic, neural and pancreatic lineage. CONCLUSIONS Healthy adult human ovaries can harbour an interesting population of cells showing typical MSCs characteristics under in vitro conditions and for this reason we named these cells putative MSCs. These cells express genes encoding main MSCs markers and have an interesting differential potential. Based on these results, we propose PO-MSCs as a novel type of MSCs which share some similarities with BM-MSCs. Nevertheless they show distinct and specific characteristics and are not fibroblasts.
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Affiliation(s)
- Martin Stimpfel
- Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slajmerjeva 3, 1000, Ljubljana, Slovenia
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Ghasemi N, Razavi S. Transdifferentiation potential of adipose-derived stem cells into neural lineage and their application. ACTA ACUST UNITED AC 2014. [DOI: 10.7243/2055-091x-1-12] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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29
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Zhao B, Sun X, Li X, Yang Q, Li Y, Zhang Y, Li B, Ma X. Improved preparation of acellular nerve scaffold and application of PKH26 fluorescent labeling combined with in vivo fluorescent imaging system in nerve tissue engineering. Neurosci Lett 2013; 556:52-7. [DOI: 10.1016/j.neulet.2013.10.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2013] [Revised: 10/11/2013] [Accepted: 10/11/2013] [Indexed: 11/16/2022]
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30
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Hou X, Liang Q, Wu Y. Transplantation of Schwann cells co-cultured with brain-derived neurotrophic factor for the treatment of experimental autoimmune neuritis. J Neuroimmunol 2013; 263:83-90. [DOI: 10.1016/j.jneuroim.2013.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 08/03/2013] [Accepted: 08/06/2013] [Indexed: 11/27/2022]
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31
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Faroni A, Rothwell SW, Grolla AA, Terenghi G, Magnaghi V, Verkhratsky A. Differentiation of adipose-derived stem cells into Schwann cell phenotype induces expression of P2X receptors that control cell death. Cell Death Dis 2013; 4:e743. [PMID: 23887634 PMCID: PMC3730438 DOI: 10.1038/cddis.2013.268] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Revised: 05/24/2013] [Accepted: 06/19/2013] [Indexed: 01/19/2023]
Abstract
Schwann cells (SCs) are fundamental for development, myelination and regeneration in the peripheral nervous system. Slow growth rate and difficulties in harvesting limit SC applications in regenerative medicine. Several molecules, including receptors for neurosteroids and neurotransmitters, have been suggested to be implicated in regulating physiology and regenerative potential of SCs. Adipose-derived stem cells (ASCs) can be differentiated into SC-like phenotype (dASC) sharing morphological and functional properties with SC, thus representing a valid SC alternative. We have previously shown that dASC express γ-aminobutyric-acid receptors, which modulate their proliferation and neurotrophic potential, although little is known about the role of other neurotransmitters in ASC. In this study, we investigated the expression of purinergic receptors in dASC. Using reverse transriptase (RT)-PCR, western blot analyses and immunocytochemistry, we have demonstrated that ASCs express P2X3, P2X4 and P2X7 purinoceptors. Differentiation of ASCs towards glial phenotype was accompanied by upregulation of P2X4 and P2X7 receptors. Using Ca(2+)-imaging techniques, we have shown that stimulation of purinoceptors with adenosine 5'-triphosphate (ATP) triggers intracellular Ca(2+) signals, indicating functional activity of these receptors. Whole-cell voltage clamp recordings showed that ATP and BzATP induced ion currents that can be fully inhibited with specific P2X7 antagonists. Finally, using cytotoxicity assays we have shown that the increase of intracellular Ca(2+) leads to dASC death, an effect that can be prevented using a specific P2X7 antagonist. Altogether, these results show, for the first time, the presence of functional P2X7 receptors in dASC and their link with critical physiological processes such as cell death and survival. The presence of these novel pharmacological targets in dASC might open new opportunities for the management of cell survival and neurotrophic potential in tissue engineering approaches using dASC for nerve repair.
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Affiliation(s)
- A Faroni
- Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK.
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Ou Y, Qu R, Dai J. Experimental biological research on stem cells in fascia tissue. J Acupunct Meridian Stud 2013; 6:129-33. [PMID: 23787281 DOI: 10.1016/j.jams.2013.03.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 03/11/2013] [Accepted: 03/12/2013] [Indexed: 11/18/2022] Open
Abstract
The fascia tissue, derived from the mesoderm, is distributed in all parts of the human body. It consists of connective tissues and stem cells. The fascia tissue is also believed to be a functional system, like the digestive system, in the human body, controlling self-inspection, self-maintenance, support, and storage. In addition, much of the research relevant to fascia tissue has focused on adipose-derived stem cells (ADSCs), which mainly exist in adipose tissues. The aim of this review is to summarize the current research on ADSCs, including a brief introduction of their biological characteristics, the isolation and expansion methods, a conclusion on their multidifferentiation potential, new clinical applications, and the therapeutic strategies for treating tumors.
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Affiliation(s)
- Yinghua Ou
- Department of Anatomy, Southern Medical University, Guangzhou, China
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Razavi S, Mardani M, Kazemi M, Esfandiari E, Narimani M, Esmaeili A, Ahmadi N. Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells. Cell Mol Neurobiol 2013; 33:283-9. [PMID: 23212292 PMCID: PMC11498022 DOI: 10.1007/s10571-012-9895-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Accepted: 11/16/2012] [Indexed: 12/21/2022]
Abstract
The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100β and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP(+)/S100β(+) revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries.
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Affiliation(s)
- Shahnaz Razavi
- Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
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Faroni A, Terenghi G, Reid AJ. Adipose-derived stem cells and nerve regeneration: promises and pitfalls. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2013; 108:121-36. [PMID: 24083433 DOI: 10.1016/b978-0-12-410499-0.00005-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
In order to improve the outcome of nerve regeneration following peripheral trauma injuries, the development of bioengineered nerve grafts has attracted great attention in the field of tissue engineering. Adult stem cells constitute the ideal alternative to Schwann cells (SCs) as transplantable cells in bioartificial nerve grafts. Among the various sources of stem cells with potential applications for regenerative medicine, the adipose tissue has been proven to be one of the most promising. Adipose-derived stem cells (ASCs) are easily obtained, rapidly expanded, show low immunogenicity, and can be differentiated into SCs in vitro. This chapter will focus on recent advances in the use of differentiated and undifferentiated ASCs for peripheral nerve regeneration, with a critical attention for the clinical exploitability of ASC in nerve repair strategies.
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Affiliation(s)
- Alessandro Faroni
- Faculty of Medical and Human Sciences, The University of Manchester, Blond McIndoe Laboratories, Regenerative Medicine, Institute of Inflammation and Repair, Manchester, United Kingdom.
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