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Gupta A, Singh S. Potential Role of Growth Factors Controlled Release in Achieving Enhanced Neuronal Trans-differentiation from Mesenchymal Stem Cells for Neural Tissue Repair and Regeneration. Mol Neurobiol 2021; 59:983-1001. [PMID: 34816381 DOI: 10.1007/s12035-021-02646-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 11/11/2021] [Indexed: 02/07/2023]
Abstract
With an increase in the incidence of neurodegenerative diseases, a need to replace incapable conventional methods has arisen. To overcome this burden, stem cells therapy has emerged as an efficient treatment option. Endeavours to accomplish this have paved the path to neural regeneration through efficient neuronal transdifferentiation. Despite their potential, the use of stem cells still entails several limitations, such as low differentiation efficiency and difficulties in guiding differentiation. The process of neural differentiation through the stem cells is achieved through the use of chemical inducers or growth factors and their direct introduction reduces their bioavailability in the system. To address these limitations, neural regeneration ventures require growth factors to be effectively implemented on stem cells in order to produce functional neuronal precursor cells. An efficient technique to achieve it is through the delivery of growth factors via microcarriers for their sustained release. It ensures the presence of commensurable concentration even at later stages of neuronal transdifferentiation. Nanofibers and nanoparticles, along with liposomes and such, have been used to implement this. The interaction between such carriers and the growth factors is mainly electrostatic. Such interaction enables them to form a stable assembly through immobilisation of the growth factor either onto their surfaces or within the core of their structures. The rate of sustained release depends upon the release kinetics associated with the polymeric structure employed and its interaction with the encapsulated growth factor. The sustained release ensures that the stem cells immerse under the effect of the growth factors for a prolonged period, ultimately aiding in the formation of cells showing ample characteristics of neuron precursors. This review analyses the various carriers that have been employed for the release of growth factors in an orderly fashion and their constituents, along with the advantages and the limitations they pose in delivering the growth factors for facilitating the process of neuronal transdifferentiation.
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Affiliation(s)
- Ayushi Gupta
- Applied Science Department, Indian Institute of Information Technology, Allahabad, UP, India
| | - Sangeeta Singh
- Applied Science Department, Indian Institute of Information Technology, Allahabad, UP, India.
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Brennan MÁ, Barilani M, Rusconi F, de Lima J, Vidal L, Lavazza C, Lazzari L, Giordano R, Layrolle P. Chondrogenic and BMP-4 primings confer osteogenesis potential to human cord blood mesenchymal stromal cells delivered with biphasic calcium phosphate ceramics. Sci Rep 2021; 11:6751. [PMID: 33762629 PMCID: PMC7991626 DOI: 10.1038/s41598-021-86147-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 02/24/2021] [Indexed: 12/15/2022] Open
Abstract
Bone marrow mesenchymal stem/stromal cells (BMSCs) show great promise for bone repair, however they are isolated by an invasive bone marrow harvest and their regenerative potential decreases with age. Conversely, cord blood can be collected non-invasively after birth and contains MSCs (CBMSCs) that can be stored for future use. However, whether CBMSCs can replace BMSCs targeting bone repair is unknown. This study evaluates the in vitro osteogenic potential of unprimed, osteogenically primed, or chondrogenically primed CBMSCs and BMSCs and their in vivo bone forming capacity following ectopic implantation on biphasic calcium phosphate ceramics in nude mice. In vitro, alkaline phosphatase (intracellular, extracellular, and gene expression), and secretion of osteogenic cytokines (osteoprotegerin and osteocalcin) was significantly higher in BMSCs compared with CBMSCs, while CBMSCs demonstrated superior chondrogenic differentiation and secretion of interleukins IL-6 and IL-8. BMSCs yielded significantly more cell engraftment and ectopic bone formation compared to CBMSCs. However, priming of CBMSCs with either chondrogenic or BMP-4 supplements led to bone formation by CBMSCs. This study is the first direct quantification of the bone forming abilities of BMSCs and CBMSCs in vivo and, while revealing the innate superiority of BMSCs for bone repair, it provides avenues to induce osteogenesis by CBMSCs.
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Affiliation(s)
- Meadhbh Á Brennan
- Inserm, UMR 1238, PHY-OS Laboratory, Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France
- National University of Ireland (NUIG), Galway, Ireland
| | - Mario Barilani
- Laboratory of Regenerative Medicine-Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco Rusconi
- Laboratory of Regenerative Medicine-Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Julien de Lima
- Inserm, UMR 1238, PHY-OS Laboratory, Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France
| | - Luciano Vidal
- Inserm, UMR 1238, PHY-OS Laboratory, Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France
- Rapid Manufacturing Platform, GEM Laboratory, Centrale Nantes, Nantes, France
| | - Cristiana Lavazza
- Laboratory of Regenerative Medicine-Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenza Lazzari
- Laboratory of Regenerative Medicine-Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rosaria Giordano
- Laboratory of Regenerative Medicine-Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pierre Layrolle
- Inserm, UMR 1238, PHY-OS Laboratory, Bone Sarcomas and Remodelling of Calcified Tissues, Faculty of Medicine, University of Nantes, Nantes, France.
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Mankuzhy PD, Ramesh ST, Thirupathi Y, Mohandas PS, Chandra V, Sharma TG. The preclinical and clinical implications of fetal adnexa derived mesenchymal stromal cells in wound healing therapy. Wound Repair Regen 2021; 29:347-369. [PMID: 33721373 DOI: 10.1111/wrr.12911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 12/06/2020] [Accepted: 03/01/2021] [Indexed: 11/28/2022]
Abstract
Mesenchymal stromal cells (MSCs) isolated from fetal adnexa namely amniotic membrane/epithelium, amniotic fluid and umbilical cord have hogged the limelight in recent times, as a proposed alternative to MSCs from conventional sources. These cells which are identified as being in a developmentally primitive state have many advantages, the most important being the non-invasive nature of their isolation procedures, absence of ethical concerns, proliferation potential, differentiation abilities and low immunogenicity. In the present review, we are focusing on the potential preclinical and clinical applications of different cell types of fetal adnexa, in wound healing therapy. We also discuss the isolation-culture methods, cell surface marker expression, multi-lineage differentiation abilities, immune-modulatory capabilities and their homing property. Different mechanisms involved in the wound healing process and the role of stromal cells in therapeutic wound healing are highlighted. Further, we summarize the findings of the cell delivery systems in skin lesion models and paracrine functions of their secretome in the wound healing process. Overall, this holistic review outlines the research findings of fetal adnexa derived MSCs, their usefulness in wound healing therapy in human as well as in veterinary medicine.
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Affiliation(s)
- Pratheesh D Mankuzhy
- Department of Physiology, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India
| | - Sreekumar T Ramesh
- Department of Physiology, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, India
| | - Yasotha Thirupathi
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
| | - Ponny S Mohandas
- Consultant Gynecologist, Department of Gynecology and Obstetrics, Meditrina Hospital, Ayathil, Kollam, Kerala, India
| | - Vikash Chandra
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
| | - Taru Guttula Sharma
- Physiology & Climatology Division, ICAR-Indian Veterinary Research Institute (Deemed University), Izatnagar, Uttar Pradesh, India
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Um S, Ha J, Choi SJ, Oh W, Jin HJ. Prospects for the therapeutic development of umbilical cord blood-derived mesenchymal stem cells. World J Stem Cells 2020; 12:1511-1528. [PMID: 33505598 PMCID: PMC7789129 DOI: 10.4252/wjsc.v12.i12.1511] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/23/2020] [Accepted: 11/12/2020] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord blood (UCB) is a primitive and abundant source of mesenchymal stem cells (MSCs). UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and disorders. Despite the high latent self-renewal and differentiation capacity of these cells, the safety, efficacy, and yield of MSCs expanded for ex vivo clinical applications remains a concern. However, immunomodulatory effects have emerged in various disease models, exhibiting specific mechanisms of action, such as cell migration and homing, angiogenesis, anti-apoptosis, proliferation, anti-cancer, anti-fibrosis, anti-inflammation and tissue regeneration. Herein, we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies, and discuss the concerns regarding the safety and mass production issues in future applications.
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Affiliation(s)
- Soyoun Um
- Research Team for Immune Cell Therapy, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Jueun Ha
- Research Team for Osteoarthritis, Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Soo Jin Choi
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Wonil Oh
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
| | - Hye Jin Jin
- Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, South Korea
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Kargozar S, Mozafari M, Hamzehlou S, Brouki Milan P, Kim HW, Baino F. Bone Tissue Engineering Using Human Cells: A Comprehensive Review on Recent Trends, Current Prospects, and Recommendations. APPLIED SCIENCES 2019; 9:174. [DOI: 10.3390/app9010174] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The use of proper cells for bone tissue engineering remains a major challenge worldwide. Cells play a pivotal role in the repair and regeneration of the bone tissue in vitro and in vivo. Currently, a large number of differentiated (somatic) and undifferentiated (stem) cells have been used for bone reconstruction alone or in combination with different biomaterials and constructs (e.g., scaffolds). Although the results of the cell transplantation without any supporting or adjuvant material have been very effective with regard to bone healing. Recent advances in bone scaffolding are now becoming new players affecting the osteogenic potential of cells. In the present study, we have critically reviewed all the currently used cell sources for bone reconstruction and discussed the new horizons that are opening up in the context of cell-based bone tissue engineering strategies.
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Affiliation(s)
- Saeid Kargozar
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad 917794-8564, Iran
| | - Masoud Mozafari
- Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran 14155-4777, Iran
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran 144961-4535, Iran
| | - Sepideh Hamzehlou
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran 14155-6447, Iran
- Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Peiman Brouki Milan
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran 144961-4535, Iran
| | - Hae-Won Kim
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Korea
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine Research Center, Dankook University, Cheonan 31116, Korea
| | - Francesco Baino
- Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
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Wang O, Ismail A, Fabian FM, Lin H, Li Q, Elowsky C, Carlson MA, Burgess W, Velander WH, Kidambi S, Lei Y. A totally recombinant fibrin matrix for mesenchymal stem cell culture and delivery. J Biomed Mater Res A 2018; 106:3135-3142. [PMID: 30152030 DOI: 10.1002/jbm.a.36508] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 06/15/2018] [Accepted: 07/12/2018] [Indexed: 01/14/2023]
Abstract
Mesenchymal stem cells (MSCs) have been widely studied for tissue engineering and treating diseases in laboratories, clinical trials, and clinics. Fibrin matrices are often used to culture MSCs or increase the retention of MSCs at the injection site. However, fibrins made with the human plasma derived fibrinogen have high cost and risk of human pathogen transmission. In this article, we studied if fibrin matrices made with recombinant human fibrinogen, recombinant human thrombin, and recombinant human factor XIII could be used to culture and deliver MSCs. We systematically investigated the relationships between the fibrin matrix formulation, its nanostructure, and the behaviors of the cells in the matrix including the cell morphology, viability, and growth. We found that the fibrinogen concentration significantly affected the matrix structure and cell behaviors. We then used an optimized fibrin matrix to deliver human MSCs into mice subcutaneously. We found that the matrix could significantly enhance the retention of MSCs at the injection site. To our best knowledge, this is the first study on using fibrin matrices made with entirely recombinant proteins for culturing and delivering MSCs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3135-3142, 2018.
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Affiliation(s)
- Ou Wang
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska.,Biomedical Engineering Program, University of Nebraska, Lincoln, Nebraska
| | - Ayman Ismail
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - Frank Marco Fabian
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - Haishuang Lin
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - Qiang Li
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - Christian Elowsky
- Department of Agronomy and Horticulture, University of Nebraska, Lincoln, Nebraska
| | - Mark A Carlson
- Department of Surgery, University of Nebraska Medical Center and the Omaha VA Medical Center, Omaha, Nebraska
| | - Wilson Burgess
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - William H Velander
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska
| | - Srivatsan Kidambi
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska.,Biomedical Engineering Program, University of Nebraska, Lincoln, Nebraska.,Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska.,Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska
| | - Yuguo Lei
- Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, Nebraska.,Biomedical Engineering Program, University of Nebraska, Lincoln, Nebraska.,Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska.,Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska
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7
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Gasparotto VPO, Landim-Alvarenga FC, Oliveira ALR, Simões GF, Lima-Neto JF, Barraviera B, Ferreira RS. A new fibrin sealant as a three-dimensional scaffold candidate for mesenchymal stem cells. Stem Cell Res Ther 2014; 5:78. [PMID: 24916098 PMCID: PMC4100340 DOI: 10.1186/scrt467] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 12/02/2013] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION The optimization of an organic scaffold for specific types of applications and cells is vital to successful tissue engineering. In this study, we investigated the effects of a new fibrin sealant derived from snake venom as a scaffold for mesenchymal stem cells, to demonstrate the ability of cells to affect and detect the biological microenvironment. METHODS The characterization of CD34, CD44 and CD90 expression on mesenchymal stem cells was performed by flow cytometry. In vitro growth and cell viability were evaluated by light and electron microscopy. Differentiation into osteogenic, adipogenic and chondrogenic lineages was induced. RESULTS The fibrin sealant did not affect cell adhesion, proliferation or differentiation and allowed the adherence and growth of mesenchymal stem cells on its surface. Hoechst 33342 and propidium iodide staining demonstrated the viability of mesenchymal stem cells in contact with the fibrin sealant and the ability of the biomaterial to maintain cell survival. CONCLUSIONS The new fibrin sealant is a three-dimensional scaffolding candidate that is capable of maintaining cell survival without interfering with differentiation, and might also be useful in drug delivery. Fibrin sealant has a low production cost, does not transmit infectious diseases from human blood and has properties of a suitable scaffold for stem cells because it permits the preparation of differentiated scaffolds that are suitable for every need.
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Jo CH, Yoon PW, Kim H, Kang KS, Yoon KS. Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model. Cell Tissue Res 2013; 353:41-52. [PMID: 23624634 DOI: 10.1007/s00441-013-1619-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Accepted: 03/13/2013] [Indexed: 11/27/2022]
Abstract
Mesenchymal stem cells (MSCs) can be obtained from various sources. MSCs from different origins appear to have different preferences for differentiation. In this study, we have compared the in vivo osteogenic potential of adult MSCs from adipose tissue (AT) and bone marrow (BM) with fetal MSCs from umbilical cord (UC) and umbilical cord blood (UCB) by using a rat critical-sized femoral defect model. We have also sought to determine whether pretreatment with an osteogenic medium promotes osteogenesis in MSCs. Study groups were divided as follows: (1) defect only, (2) scaffold only, (3) AT MSCs in scaffolds, (4) BM MSCs in scaffolds, (5) UC MSCs in scaffolds and (6) UCB MSCs in scaffolds. Groups with MSCs were further divided with respect to their pretreatment. At 12 weeks after surgery, in vivo osteogenesis was measured radiographically and by micro-computed tomography (CT). Based on quantitative assessment by micro-CT, no significant difference of the mean bone volume fraction value (BV/TV) was seen between adult MSCs (AT and BM MSCs) and fetal MSCs (UC and UCB MSCs). The mean BV/TVs were significantly higher in non-pretreated BM MSC (14.2±1.4%) and UCB MSC (14.0±1.2%) and pretreated UC MSC (14.8±2.0%) than in those with the scaffold only (11.3±1.3%; P<0.05). In addition, AT (from 10.4±1.2% to 13.1±2.2%) and UC (from 10.3±0.7% to 14.8±2.0%) MSCs from solid tissues showed a significant increase in the mean BV/TV with pretreatment (P<0.05). In contrast, BM MSC (from 14.2±1.4% to 10.9±1.2%) and UCB MSC (from 14.0±1.2% to 11.6±1.0%) from non-solid tissues showed a significant decrease with pretreatment (P<0.05).
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Affiliation(s)
- Chris Hyunchul Jo
- Department of Orthopedic Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 20 Boramae-Ro, 5-Gil, Dongjak-Gu, Seoul, 156-707, South Korea.
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Differentiation of Human Dermal Mesenchymal Stem Cells into Cardiomyocytes by Treatment with 5-Azacytidine: Concept for Regenerative Therapy in Myocardial Infarction. ACTA ACUST UNITED AC 2013. [DOI: 10.1155/2013/687282] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Myocardial infarction (MI) is the leading cause of death worldwide. Stem cells regenerative medicine offers a promising approach to cure such degenerative disorders. Mesenchymal stem cells are thought to be one of the important types of stem cells which can differentiate into various lineages such as neuron, hepatocytes, and cardiomyocytes. In the present study, human dermal mesenchymal stem cells (hDMSCs) have been developed from human scalp punch biopsy and characterized for their mesenchymal phenotype so that these cells can be useful for differentiating into cardiomyocytes. 5-Azacytidine induces cardiomyocyte differentiation in vitro and therefore it has been used to differentiate hDMSCs cells into cardiomyocytes. It was observed that hDMSCs differentiated into cardiomyocyte within a period of 4 days to 15 days after treatment with 10 μM and 20 μM of 5-azacytidine. The cardiomyocyte phenotype was confirmed by studying expression of α-cardiac actin, β-myosin heavy chain, and cardiac troponin T. Thus, this paper describes the differentiation of hDMSCs into cardiomyocytes which can be further be used for treatment of MI. This type of cell-based cardiac therapy will offer a new hope for millions of patients worldwide who are suffering from heart disease.
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Li J, Lepski G. Cell transplantation for spinal cord injury: a systematic review. BIOMED RESEARCH INTERNATIONAL 2013; 2013:786475. [PMID: 23484157 PMCID: PMC3581246 DOI: 10.1155/2013/786475] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/10/2012] [Revised: 11/16/2012] [Accepted: 12/11/2012] [Indexed: 02/07/2023]
Abstract
Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studied in vitro in detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a "bench to bedside" gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cells, axonal regeneration and remyelination, sensory and motor functional recovery, and electrophysiological improvements. Finally we also review the literature on the in vivo tracking techniques for transplanted cells.
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Affiliation(s)
- Jun Li
- Department of Neurosurgery, Eberhard Karls University, 72076 Tübingen, Germany
- Department of Spine Surgery, The Affiliated Hospital of Luzhou Medical College, 646000 Luzhou, China
| | - Guilherme Lepski
- Department of Neurosurgery, Eberhard Karls University, 72076 Tübingen, Germany
- Division of Neurosurgery, Department of Neurology, Faculdade de Medicina, Universidade de São Paulo, Avnida Dr. Enéas de Carvalho Aguiar 255, 05403-000 São Paulo, SP, Brazil
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Aly H, Mohsen L, Badrawi N, Gabr H, Ali Z, Akmal D. Viability and neural differentiation of mesenchymal stem cells derived from the umbilical cord following perinatal asphyxia. J Perinatol 2012; 32:671-6. [PMID: 22134676 DOI: 10.1038/jp.2011.174] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Hypoxia-ischemia is the leading cause of neurological handicaps in newborns worldwide. Mesenchymal stem cells (MSCs) collected from fresh cord blood of asphyxiated newborns have the potential to regenerate damaged neural tissues. The aim of this study was to examine the capacity for MSCs to differentiate into neural tissue that could subsequently be used for autologous transplantation. STUDY DESIGN We collected cord blood samples from full-term newborns with perinatal hypoxemia (n=27), healthy newborns (n=14) and non-hypoxic premature neonates (n=14). Mononuclear cells were separated, counted, and then analyzed by flow cytometry to assess various stem cell populations. MSCs were isolated by plastic adherence and characterized by morphology. Cells underwent immunophenotyping and trilineage differentiation potential. They were then cultured in conditions favoring neural differentiation. Neural lineage commitment was detected using immunohistochemical staining for glial fibrillary acidic protein, tubulin III and oligodendrocyte marker O4 antibodies. RESULT Mononuclear cell count and viability did not differ among the three groups of infants. Neural differentiation was best demonstrated in the cells derived from hypoxia-ischemia term neonates, of which 69% had complete and 31% had partial neural differentiation. Cells derived from preterm neonates had the least amount of neural differentiation, whereas partial differentiation was observed in only 12%. CONCLUSION These findings support the potential utilization of umbilical cord stem cells as a source for autologous transplant in asphyxiated neonates.
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Affiliation(s)
- H Aly
- Department of Newborn Services, George Washington University and Children's National Medical Center, Washington, DC 20037, USA.
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Eslaminejad MB, Taghiyar L. Study of the structure of canine mesenchymal stem cell osteogenic culture. Anat Histol Embryol 2012; 39:446-55. [PMID: 20594192 DOI: 10.1111/j.1439-0264.2010.01013.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
This study was designed to investigate the morphological features of osteogenic cultures that were established from canine marrow derived-mesenchymal stem cells (MSCs). Tripotent canine MSCs were plated in osteogenic conditions for 3 weeks, at the end of which the cultures were observed by light and transmission electron microscopy. Alkaline phosphatase (ALP) activity of the culture was determined during the differentiation period. To assess whether endochondral or intramembranous ossification was involved in MSC bone differentiation, the cultures were explored for cartilage-related gene expression. Multiple nodule-like cell aggregates appeared to form in the osteogenic cultures. These nodules were covered by a periosteum-like layer and osteocyte-like cells of varying morphology were located in lacuna-like cavities within the nodule mass. Furthermore, the bone nodules possessed an abundant matrix in which clearly striated collagen I fibres were arranged in perpendicular bundles. Matrix vesicles involving in matrix mineralization were evident in the nodules. This was in accordance with increased ALP activity in the culture. No expression of cartilage-related genes was observed, which suggested that osteogenesis might occur by intramembranous ossification. In conclusion, canine MSCs could be an appropriate model for studying in vitro bone development.
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Affiliation(s)
- M B Eslaminejad
- Department of Stem Cell and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
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13
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Fadel L, Viana BR, Feitosa MLT, Ercolin ACM, Roballo KCS, Casals JB, Pieri NCG, Meirelles FV, Martins DDS, Miglino MA, Ambrósio CE. Protocols for obtainment and isolation of two mesenchymal stem cell sources in sheep. Acta Cir Bras 2012; 26:267-73. [PMID: 21808838 DOI: 10.1590/s0102-86502011000400004] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Accepted: 03/18/2011] [Indexed: 12/25/2022] Open
Abstract
PURPOSE To evaluate different protocols to isolate stem cells from ovine umbilical cord blood and adipose tissue. METHODS There were used 5 samples of umbilical blood and 5 samples of perirenal adipose tissue from 10 female sheep. All the samples were obtained through surgery, to harvest aseptic samples. There were used 3 protocols for obtainment and culture of umbilical cord blood stem cells and 4 protocols for ovine adipose tissue stem cells. RESULTS It was possible to observe only one successful protocol for the obtainment of umbilical cord blood stem cells. When analyzing the techniques used to obtain adipose tissue stem cells, only one of the methods was effective as well. Through colony forming unit assay, there were obtained 58 colonies of cells after seven days in culture. Flow citometry tests revealed the cells were positive to CD44 and exhibited negative reaction to CD38, CD45, CD41/61. These cells showed a growth curve with very well defined phases LOG, LAG and PLATEAU. This phases are typically seem in mesenchymal stem cells growth curves. CONCLUSIONS The isolation and culture of mesenchymal stem cells from ovine umbilical cord blood are complex and request more detailed assays. Stem cells from fat tissue sheep showed mesenchymal characteristics, according to their cell growth curve, ability to origin colonies of fibroblastoid cells and positive reactivity with the antibody CD44 by flow citometry.
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Affiliation(s)
- Leandro Fadel
- Surgery Department, Faculty of Veterinary Medicine and Animal Science, USP, Sao Paulo, Brazil
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14
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Mesenchymal stem cells from umbilical cord blood: parameters for isolation, characterization and adipogenic differentiation. Cytotechnology 2012; 64:511-21. [PMID: 22328147 DOI: 10.1007/s10616-012-9428-3] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Accepted: 01/03/2012] [Indexed: 12/19/2022] Open
Abstract
Isolation of mesenchymal stem cells (MSCs) from umbilical cord blood (UCB) from full-term deliveries is a laborious, time-consuming process that results in a low yield of cells. In this study we identified parameters that can be helpful for a successful isolation of UCB-MSCs. According to our findings, chances for a well succeeded isolation of these cells are higher when MSCs were isolated from UCB collected from normal full-term pregnancies that did not last over 37 weeks. Besides the duration of pregnancy, blood volume and storage period of the UCB should also be considered for a successful isolation of these cells. Here, we found that the ideal blood volume collected should be above 80 mL and the period of storage should not exceed 6 h. We characterized UCB-MSCs by morphologic, immunophenotypic, protein/gene expression and by adipogenic differentiation potential. Isolated UCB-MSCs showed fibroblast-like morphology and the capacity of differentiating into adipocyte-like cells. Looking for markers of the undifferentiated status of UCB-MSCs, we analyzed the UCB-MSCs' protein expression profile along different time periods of the differentiation process into adipocyte-like cells. Our results showed that there is a decrease in the expression of the markers CD73, CD90, and CD105 that correlates to the degree of differentiation of UCB-MSCs We suggest that CD90 can be used as a mark to follow the differentiation commitment degree of MSCs. Microarray results showed an up-regulation of genes related to the adipogenesis process and to redox metabolism in the adipocyte-like differentiated MSCs. Our study provides information on a group of parameters that may help with successful isolation and consequently with characterization of the differentiated/undifferentiated status of UCB-MSCs, which will be useful to monitor the differentiation commitment of UCB-MSC and further facilitate the application of those cells in stem-cell therapy.
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15
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Di GH, Jiang S, Li FQ, Sun JZ, Wu CT, Hu X, Duan HF. Human umbilical cord mesenchymal stromal cells mitigate chemotherapy-associated tissue injury in a pre-clinical mouse model. Cytotherapy 2012; 14:412-22. [PMID: 22242830 DOI: 10.3109/14653249.2011.646044] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND AIMS Mesenchymal stromal cells (MSC) have been shown to be a promising candidate for tissue regeneration and cancer therapy. However, their therapeutic potential against chemotherapy-induced side-effects remains unclear. METHODS We treated murine Lewis lung carcinoma (LLC) and xenograft human colon tumors with adriamycin (ADM) for 3 consecutive days followed by one intravenous (i.v.) injection of human umbilical cord (hUC) MSC for several cycles. RESULTS MSC treatment mitigated ADM-induced cardiomyopathy, reduced the extent of ADM-induced apoptosis in intestinal crypts, suppressed body weight loss in mice treated with ADM and increased the survival rate of mice treated with a lethal dose of ADM. The examination of hematologic parameters indicated a moderate recovery in MSC-injected mice. Systemic administration of MSC did not increase the growth of murine LLC cells and human colon carcinoma in vivo while it strongly inhibited the lung metastases of LLC cells. CONCLUSIONS We evaluated the prophylactic and therapeutic action of hUC MSC on the chemotherapy agent ADM-induced side-effects in two different tumor models. Our observations suggest that MSC can be used as auxiliary means in chemotherapy for certain tumor types.
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Affiliation(s)
- Guo-Hu Di
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
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16
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Sun HP, Zhang X, Chen XH, Zhang C, Gao L, Feng YM, Peng XG, Gao L. Human umbilical cord blood-derived stromal cells are superior to human umbilical cord blood-derived mesenchymal stem cells in inducing myeloid lineage differentiation in vitro. Stem Cells Dev 2011; 21:1429-40. [PMID: 22023173 DOI: 10.1089/scd.2011.0348] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Stromal cells and mesenchymal stem cells (MSCs), 2 important cell populations within the hematopoietic microenvironment, may play an important role in the development of hematopoietic stem/progenitor cells. We have successfully cultured human umbilical cord blood-derived stromal cells (hUCBDSCs). It has been demonstrated that MSCs also exist in hUCB. However, we have not found any reports on the distinct characteristics of hUCBDSCs and human umbilical cord blood-derived mesenchymal stem cells (hUCBDMSCs). In this study, hUCBDSCs and hUCBDMSCs were isolated from the cord blood of full-term infants using the same density gradient centrifugation and cultured in the appropriate medium. Some biological characteristics and hematopoietic supportive functions were compared in vitro. hUCBDSCs were distinct from hUCBDMSCs in morphology, proliferation, cell cycle, passage, immunophenotype, and the capacity for classical tri-lineage differentiation. Finally, quantitative real-time polymerase chain reaction analysis revealed that granulocyte colony-stimulating factor (G-CSF) gene expression was higher in hUCBDSCs than that in hUCBDMSCs. Enzyme-linked immunosorbent assay revealed that the secretion of G-CSF, thrombopoietin (TPO), and granulocyte macrophage colony-stimulating factor (GM-CSF) by hUCBDSCs was higher than that by hUCBDMSCs. After coculture, the granulocyte/macrophage colony-forming units (CFU-GM) of hematopoietic cells from the hUCBDSC feeder layer was more than that from the hUCBDMSC feeder layer. Flow cytometry was used to detect CD34(+) hematopoietic stem/progenitor cell committed differentiation during 14 days of coculture; the results demonstrated that CD14 and CD33 expression in hUCBDSCs was significantly higher than their expression in hUCBDMSCs. This observation was also true for the granulocyte lineage marker, CD15. This marker was expressed beginning at day 7 in hUCBDSCs. It was expressed earlier and at a higher level in hUCBDSCs compared with hUCBDMSCs. In conclusion, hUCBDSCs are different from hUCBDMSCs. hUCBDSCs are superior to hUCBDMSCs in supporting hematopoiesis stem/progenitor cells differentiation into myeloid lineage cells at an early stage in vitro.
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Affiliation(s)
- Hao-Ping Sun
- Department of Hematology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China
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17
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Liu G, Ye X, Zhu Y, Li Y, Sun J, Cui L, Cao Y. Osteogenic differentiation of GFP-labeled human umbilical cord blood derived mesenchymal stem cells after cryopreservation. Cryobiology 2011; 63:125-8. [PMID: 21684270 DOI: 10.1016/j.cryobiol.2011.05.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2010] [Revised: 05/17/2011] [Accepted: 05/31/2011] [Indexed: 12/30/2022]
Abstract
The osteogenic capacity of human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) has been demonstrated both in vitro and in vivo. Therefore, cell labeling and storage are becoming necessary for researching the potential therapeutic use of UCB-MSCs for bone tissue engineering. The aim of this study was to determine the effect of cryopreservation on the osteogenic differentiation of green fluorescent protein (GFP)-marked UCB-MSCs in vitro. MSCs were isolated from full-term human UCB, expanded, transfected with the GFP gene, and then cryopreserved in liquid nitrogen for 4 weeks. After thawing, cell surface antigen markers and osteogenic potential were analyzed, and the luminescence of these cells was observed by fluorescence microscopy. The results demonstrate that cryopreservation has no effect on the cell phenotype, GFP expression or osteogenic differentiation of UCB-MSCs, showing that cryopreserved GFP-labeled UCB-MSCs might be applied for bone tissue engineering.
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Affiliation(s)
- Guangpeng Liu
- Department of Plastic and Reconstructive Surgery, Shanghai 10th People's Hospital, Shanghai 200072, China
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18
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Khorshied MM, Gouda HM, Shaheen IA, Al Bolkeny TN. The osteogenic differentiation potentials of umbilical cord blood hematopoietic stem cells. ACTA ACUST UNITED AC 2010. [DOI: 10.1007/s00580-010-1115-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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19
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Malgieri A, Kantzari E, Patrizi MP, Gambardella S. Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med 2010; 3:248-69. [PMID: 21072260 PMCID: PMC2971538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2010] [Accepted: 09/07/2010] [Indexed: 05/30/2023]
Abstract
Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in all tissues, as part of the perivascular population. As multipotent cells, MSCs can differentiate into different tissues originating from mesoderm ranging from bone and cartilage, to cardiac muscle. MSCs are an excellent candidate for cell therapy because they are easily accessible, their isolation is straightforward, they can be bio-preserved with minimal loss of potency, and they have shown no adverse reactions to allogeneic versus autologous MSCs transplants. Therefore, MSCs are being explored to regenerate damaged tissue and treat inflammation, resulting from cardiovascular disease and myo-cardial infarction (MI), brain and spinal cord injury, stroke, diabetes, cartilage and bone injury, Crohn's disease and graft versus host disease (GvHD). Most of the application and clinical trials involve MSCs from bone marrow (BMMSCs). Transplantation of MSCs from bone marrow is considered safe and has been widely tested in clinical trials of cardiovascular, neurological, and immunological disease with encouraging results. There are examples of MSCs utilization in the repair of kidney, muscle and lung. The cells were also found to promote angiogenesis, and were used in chronic skin wound treatment. Recent studies involve also mesenchymal stem cell transplant from umbilical cord (UCMSCt). One of these demonstrate that UCMSCt may improve symptoms and biochemical values in patients with severe refractory systemic lupus erythematosus (SLE), and therefore this source of MSCs need deeper studies and require more attention. However, also if there are 79 registered clinical trial sites for evaluating MSC therapy throughout the world, it is still a long way to go before using these cells as a routinely applied therapy in clinics.
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Affiliation(s)
- Arianna Malgieri
- Department of Biopathology, Genetics Unit, Tor Vergata University of RomeItaly
| | | | | | - Stefano Gambardella
- Department of Biopathology, Genetics Unit, Tor Vergata University of RomeItaly
- Bios InternationalRome, Italy
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20
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21
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Liu G, Li Y, Sun J, Zhou H, Zhang W, Cui L, Cao Y. In vitro and in vivo evaluation of osteogenesis of human umbilical cord blood-derived mesenchymal stem cells on partially demineralized bone matrix. Tissue Eng Part A 2010; 16:971-82. [PMID: 19839720 DOI: 10.1089/ten.tea.2009.0516] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The osteogenic differentiation potential of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) has been documented previously, and partially demineralized bone matrix (pDBM) represents a promising candidate for bone tissue engineering scaffolds. In this study, pDBM scaffolds derived from porcine cancellous bone were evaluated for their ability to support human UCB-MSCs osteogenic differentiation in vitro and bone-forming capacity in vivo to assess the potential use of UCB-MSCs in bone tissue engineering applications. MSCs were isolated from full-term human UCB and expanded, and their cell surface antigen markers and multilineage capability to differentiate into osteoblasts, chondrocytes, and adipocytes were analyzed. The in vitro proliferation and osteogenic differentiation of UCB-MSCs loaded onto the three-dimensional pDBM scaffolds were determined. Critical-sized full-thickness circular defects (5 mm in diameter) created bilaterally in the parietal bones of athymic rats were treated with one of the following: osteogenically induced UCB-MSC/pDBM composites (Group A, n = 8), noninduced UCB-MSC/pDBM composites (Group B, n = 8), pDBM alone (Group C, n = 8), or left untreated (Group D, n = 8). Microcomputed tomography analysis showed that new bone was formed in Group A at 6 weeks postimplantation, and greater bone volume and density were found after 12 weeks. In other groups, new bone formation was not evident after 6 weeks, and no bone union was found at 12 weeks. Histological examination revealed that the defect was repaired by tissue-engineered bone in Group A at 12 weeks, and fibrous union was observed in Groups B, C, and D. These results demonstrate that pDBM can support osteogenic differentiation of human UCB-MSCs in vitro and in vivo, and UCB-MSCs may serve as an alternative cell source for bone tissue engineering and regeneration.
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Affiliation(s)
- Guangpeng Liu
- The Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai JiaoTong Universtiy School of Medicine, Shanghai, China
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22
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Anisimov SV. Cell-based therapeutic approaches for Parkinson's disease: progress and perspectives. Rev Neurosci 2010; 20:347-81. [PMID: 20397620 DOI: 10.1515/revneuro.2009.20.5-6.347] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Motor dysfunctions in Parkinson's disease are believed to be primarily due to the degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Because a single-type cell population is depleted, Parkinson's disease is considered a primary target for cell replacement-based therapeutic strategies. Extensive studies have confirmed transplantation of donor neurons could be beneficial, yet identifying an alternative cell source is clearly essential. Human embryonic stem cells (hESCs) have been proposed as a renewable source of dopaminergic neurons for transplantation in Parkinson's disease; other potential sources could include neural stem cells (hNSCs) and adult mesenchymal stem cells (hMSCs). However, numerous difficulties avert practical application of stem cell-based therapeutic approaches for the treatment of Parkinson's disease. Among the latter, ethical, safety (including xeno- and tumor formation-associated risks) and technical issues stand out. This review aims to provide a balanced and updated outlook on various issues associated with stem cells in regard to their potential in the treatment of Parkinson's disease. Essential features of the individual stem cell subtypes, principles of available differentiation protocols, transplantation, and safety issues are discussed extensively.
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Affiliation(s)
- Sergey V Anisimov
- Department of Intracellular Signalling and Transport, Institute of Cytology, Russian Academy of Sciences and Research, Saint-Petersburg, Russia.
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23
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Toai TC, Thao HD, Gargiulo C, Thao NP, Thuy TTT, Tuan HM, Tung NT, Filgueira L, Strong DM. In vitro culture of Keratinocytes from human umbilical cord blood mesenchymal stem cells: the Saigonese culture. Cell Tissue Bank 2010; 12:125-33. [DOI: 10.1007/s10561-010-9174-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2010] [Accepted: 03/03/2010] [Indexed: 10/19/2022]
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24
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Parenteau NL. Commercial development of cell-based therapeutics: strategic considerations along the drug to tissue spectrum. Regen Med 2009; 4:601-11. [PMID: 19580408 DOI: 10.2217/rme.09.29] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
In cell-based therapy, the process defines the product and the biological interaction between implant and host determines the outcome. Developing the optimum combination of process, product and a clinically relevant effect has been a challenge, leaving many potential therapies stalled in early clinical studies. This special report discusses pivotal factors in the development of cell-based technologies, irrespective of where they fit on the spectrum from cell-based drug to tissue construct, and how we can ensure delivery of an effective product to the clinic and the marketplace. Epidermal cell-based therapies serve as an historical lesson.
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Affiliation(s)
- Nancy L Parenteau
- Parenteau BioConsultants, LLC, PO Box 448, Fair Haven, VT 05743, USA.
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25
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Snykers S, De Kock J, Rogiers V, Vanhaecke T. In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 2009; 27:577-605. [PMID: 19056906 PMCID: PMC2729674 DOI: 10.1634/stemcells.2008-0963] [Citation(s) in RCA: 193] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Stem cells are a unique source of self-renewing cells within the human body. Before the end of the last millennium, adult stem cells, in contrast to their embryonic counterparts, were considered to be lineage-restricted cells or incapable of crossing lineage boundaries. However, the unique breakthrough of muscle and liver regeneration by adult bone marrow stem cells at the end of the 1990s ended this long-standing paradigm. Since then, the number of articles reporting the existence of multipotent stem cells in skin, neuronal tissue, adipose tissue, and bone marrow has escalated, giving rise, both in vivo and in vitro, to cell types other than their tissue of origin. The phenomenon of fate reprogrammation and phenotypic diversification remains, though, an enigmatic and rare process. Understanding how to control both proliferation and differentiation of stem cells and their progeny is a challenge in many fields, going from preclinical drug discovery and development to clinical therapy. In this review, we focus on current strategies to differentiate embryonic, mesenchymal(-like), and liver stem/progenitor cells into hepatocytes in vitro. Special attention is paid to intracellular and extracellular signaling, genetic modification, and cell-cell and cell-matrix interactions. In addition, some recommendations are proposed to standardize, optimize, and enrich the in vitro production of hepatocyte-like cells out of stem/progenitor cells.
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Affiliation(s)
- Sarah Snykers
- Department of Toxicology, Vrije Universiteit Brussel, Belgium.
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26
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Snykers S, Henkens T, De Rop E, Vinken M, Fraczek J, De Kock J, De Prins E, Geerts A, Rogiers V, Vanhaecke T. Role of epigenetics in liver-specific gene transcription, hepatocyte differentiation and stem cell reprogrammation. J Hepatol 2009; 51:187-211. [PMID: 19457566 DOI: 10.1016/j.jhep.2009.03.009] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Controlling both growth and differentiation of stem cells and their differentiated somatic progeny is a challenge in numerous fields, from preclinical drug development to clinical therapy. Recently, new insights into the underlying molecular mechanisms have unveiled key regulatory roles of epigenetic marks driving cellular pluripotency, differentiation and self-renewal/proliferation. Indeed, the transcription of genes, governing cell-fate decisions during development and maintenance of a cell's differentiated status in adult life, critically depends on the chromatin accessibility of transcription factors to genomic regulatory and coding regions. In this review, we discuss the epigenetic control of (liver-specific) gene-transcription and the intricate interplay between chromatin modulation, including histone (de)acetylation and DNA (de)methylation, and liver-enriched transcription factors. Special attention is paid to their role in directing hepatic differentiation of primary hepatocytes and stem cells in vitro.
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Affiliation(s)
- Sarah Snykers
- Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
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27
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Toai TC, Thao HD, Thao NP, Gargiulo C, Ngoc PK, Van PH, Strong DM. In vitro culture and differentiation of osteoblasts from human umbilical cord blood. Cell Tissue Bank 2009; 11:269-80. [DOI: 10.1007/s10561-009-9141-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2009] [Accepted: 06/14/2009] [Indexed: 02/06/2023]
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28
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Barachini S, Trombi L, Danti S, D'Alessandro D, Battolla B, Legitimo A, Nesti C, Mucci I, D'Acunto M, Cascone MG, Lazzeri L, Mattii L, Consolini R, Petrini M. Morpho-functional characterization of human mesenchymal stem cells from umbilical cord blood for potential uses in regenerative medicine. Stem Cells Dev 2009; 18:293-305. [PMID: 18444788 DOI: 10.1089/scd.2008.0017] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Mesenchymal stem cells (MSCs) represent a promising source of progenitor cells having the potential to repair and to regenerate diseased or damaged skeletal tissues. Bone marrow (BM) has been the first source reported to contain MSCs. However, BM-derived cells are not always acceptable, due to the highly invasive drawing and the decline in MSC number and differentiative capability with increasing age. Human umbilical cord blood (UCB), obtainable by donation with a noninvasive method, has been introduced as an alternative source of MSCs. Here human UCB-derived MSCs isolation and morpho-functional characterization are reported. Human UCB-derived mononuclear cells, obtained by negative immunoselection, exhibited either an osteoclast-like or a mesenchymal-like phenotype. However, we were able to obtain homogeneous populations of MSCs that displayed a fibroblast-like morphology, expressed mesenchym-related antigens and showed differentiative capacities along osteoblastic and early chondroblastic lineages. Furthermore, this study is one among a few papers investigating human UCB-derived MSC growth and differentiation on three-dimensional scaffolds focusing on their potential applications in regenerative medicine and tissue engineering. UCB-derived MSCs were proved to grow on biodegradable microfiber meshes; additionally, they were able to differentiate toward mature osteoblasts when cultured inside human plasma clots, suggesting their potential application in orthopedic surgery.
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Affiliation(s)
- Serena Barachini
- RRMR/CUCCS, Regional Network of Regenerative Medicine/Center for the Clinical Use of Stem Cells, University of Pisa, Pisa, Italy.
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29
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Epidermal growth factor promotes the differentiation of stem cells derived from human umbilical cord blood into neuron-like cells via taurine induction in vitro. In Vitro Cell Dev Biol Anim 2009; 45:321-7. [DOI: 10.1007/s11626-009-9184-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2008] [Accepted: 01/07/2009] [Indexed: 10/21/2022]
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Jin GZ, Yin XJ, Yu XF, Cho SJ, Lee HS, Lee HJ, Kong IK. Enhanced tyrosine hydroxylase expression in PC12 cells co-cultured with feline mesenchymal stem cells. J Vet Sci 2008; 8:377-82. [PMID: 17993752 PMCID: PMC2868154 DOI: 10.4142/jvs.2007.8.4.377] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Mesenchymal stem cells (MSCs) secrete a variety of neuroregulatory molecules, such as nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor, which upregulate tyrosine hydroxylase (TH) gene expression in PC12 cells. Enhancing TH gene expression is a critical step for treatment of Parkinson's disease (PD). The objective of this study was to assess the effects of co-culturing PC12 cells with MSCs from feline bone marrow on TH protein expression. We divided the study into three groups: an MSC group, a PC12 cell group, and the combined MSC + PC12 cell group (the co-culture group). All cells were cultured in DMEM-HG medium supplemented with 10% fetal bovine serum for three days. Thereafter, the cells were examined using western blot analysis and immunocytochemistry. In western blots, the co-culture group demonstrated a stronger signal at 60 kDa than the PC12 cell group (p<0.001). TH was not expressed in the MSC group, either in western blot or immunocytochemistry. Thus, the MSCs of feline bone marrow can up-regulate TH expression in PC12 cells. This implies a new role for MSCs in the neurodegenerative disease process.
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Affiliation(s)
- Guang-Zhen Jin
- Division of Applied Life Science, Gyeongsang National University, Jinju 660-701, Korea
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31
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Sefcik LS, Neal RA, Kaszuba SN, Parker AM, Katz AJ, Ogle RC, Botchwey EA. Collagen nanofibres are a biomimetic substrate for the serum-free osteogenic differentiation of human adipose stem cells. J Tissue Eng Regen Med 2008; 2:210-20. [PMID: 18493910 DOI: 10.1002/term.85] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Electrospinning has recently gained widespread attention as a process capable of producing nanoscale fibres that mimic native extracellular matrix. In this study, we compared the osteogenic differentiation behaviour of human adipose stem cells (ASCs) on a 3D nanofibre matrix of type I rat tail collagen (RTC) and a 2D RTC collagen-coated substrate, using a novel serum-free osteogenic medium. The serum-free medium significantly enhanced the numbers of proliferating cells in culture, compared to ASCs in traditional basal medium containing 10% animal serum, highlighting a potential clinical role for in vitro stem cell expansion. Osteogenic differentiation behaviour was assessed at days 7, 14 and 21 using quantitative real-time RT-PCR analysis of the osteogenic genes collagen I (Coll I), alkaline phosphatase (ALP), osteopontin (OP), osteonectin (ON), osteocalcin (OC) and core-binding factor-alpha (cbfa1). All genes were upregulated (>one-fold) in ASCs cultured on nanofibre scaffolds over 2D collagen coatings by day 21. Synthesis of mineralized extracellular matrix on the scaffolds was assessed on day 21 with Alizarin red staining. These studies demonstrate that 3D nanoscale morphology plays a critical role in regulating cell fate processes and in vitro osteogenic differentiation of ASCs under serum-free conditions.
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Affiliation(s)
- Lauren S Sefcik
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA
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Jin GZ, Yin XJ, Yu XF, Cho SJ, Choi EG, Lee YS, Jeon JT, Yee ST, Kong IK. Generation of neuronal-like cells from umbilical cord blood-derived mesenchymal stem cells of a RFP-transgenic cloned cat. J Vet Med Sci 2008; 70:723-6. [PMID: 18685247 DOI: 10.1292/jvms.70.723] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are multipotent adult stem cells, which can differentiation into cells of connective tissue and neural lineages. This study investigated the potential for neuronal differentiation of red fluorescent protein (RFP)-transgenic cat UCB-derived MSCs. The cells were cultured in pre-induction medium for 24 hr and in neuronal-induction medium for 72 hr. Immunofluorescent staining showed that 6.85% of the total cells were beta III-tubulin-positive, 3.37% were neurofilament light (NF-L)-positive and 7.04% were neurofilament medium (NF-M)-positive. A beta III-tubulin band was detected by western blot analysis. Our results demonstrate that RFP-transgenic UCB-derived MSCs can be differentiated into neuronal cells in vitro. Thus, RFP-transgenic MSCs could provide alternative tracing material for stem cell transplantation.
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Affiliation(s)
- Guang-Zhen Jin
- Division of Applied Life Science (BK21), Graduate School of Gyeongsang National University, Jinju, GyeongNam Province, South Korea
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Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol 2008; 251:116-23. [PMID: 18495100 DOI: 10.1016/j.cellimm.2008.04.003] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2008] [Revised: 03/29/2008] [Accepted: 04/04/2008] [Indexed: 12/12/2022]
Abstract
Mesenchymal stromal cells (MSCs) are promising candidates for developing cell therapies for intractable diseases. To assess the feasibility of transplantation with human umbilical cord blood (hUCB)-derived MSCs, we analyzed the ability of these cells to function as alloantigen-presenting cells (APC) in vitro. hUCB-MSCs were strongly positive for MSC-related antigens and stained positively for human leukocyte antigen (HLA)-AB and negatively for HLA-DR. When treated with interferon (IFN)-gamma, the expression of HLA-AB and HLA-DR, but not the co-stimulatory molecules CD80 and CD86, was increased. hUCB-MSCs did not provoke allogeneic PBMC (peripheral blood mononuclear cell) proliferation, even when their HLA-molecule expression was up-regulated by IFN-gamma pretreatment. When added to a mixed lymphocyte reaction (MLR), hUCB-MSCs actively suppressed the allogeneic proliferation of the responder lymphocytes. This suppressive effect was mediated by soluble factors. We conclude that hUCB-MSCs can suppress the allogeneic response of lymphocytes and may thus be useful in allogeneic cell therapies.
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Effect of Whole Bone Marrow Cell Infusion in the Progression of Experimental Chronic Renal Failure. Transplant Proc 2008; 40:853-5. [DOI: 10.1016/j.transproceed.2008.03.009] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Lim JH, Byeon YE, Ryu HH, Jeong YH, Lee YW, Kim WH, Kang KS, Kweon OK. Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs. J Vet Sci 2007; 8:275-82. [PMID: 17679775 PMCID: PMC2868135 DOI: 10.4142/jvs.2007.8.3.275] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.
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Affiliation(s)
- Ji Hey Lim
- Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul, Korea
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