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Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment

Authors
 Jae Hyung Kim  ;  Sang-Hyun Shin  ;  Tian Zhu Li  ;  Hwal Suh 
Citation
 JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol.10(1) : 1-13, 2016 
Journal Title
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
ISSN
 1932-6254 
Issue Date
2016
MeSH
Adult ; Azacitidine/pharmacology ; Biomimetic Materials/pharmacology* ; Cell Cycle/drug effects ; Cell Differentiation*/drug effects ; Cell Proliferation/drug effects ; Cell Separation ; Cell Shape/drug effects ; Cell Transformation, Neoplastic/drug effects* ; Cells, Cultured ; Cellular Senescence/drug effects ; Child ; Culture Media, Serum-Free/pharmacology ; Dimethyl Sulfoxide/pharmacology ; Extracellular Matrix/drug effects ; Extracellular Matrix/metabolism* ; Female ; Flow Cytometry ; Humans ; Immunohistochemistry ; Male ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/drug effects ; Myocardium/cytology ; Organogenesis/drug effects ; Phenotype ; Real-Time Polymerase Chain Reaction ; Stem Cell Niche*/drug effects
Keywords
5-azacytidine ; extracellular matrix ; mesenchymal stem cells (MSCs) ; myocardial differentiation ; senescence ; stem cell niche
Abstract
Niche appears important for preventing the spontaneous differentiation or senescence that cells undergo during in vitro expansion. In the present study, it was revealed that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) undergo senescence-related differentiation into the myocardial lineage in vitro without any induction treatment. This phenomenon occurred over the whole population of MCSs, much different from conventional differentiation with limited frequency of occurrence, and was accompanied by a change of morphology into large, flat cells with impeded proliferation, which are the representative indications of MSC senescence. By culturing MSCs under several culture conditions, it was determined that induction treatment with 5-azacytidine was not associated with the phenomenon, but the serum-starvation condition, under which proliferation is severely hampered, caused senescence progression and upregulation of cardiac markers. Nevertheless, MSCs gradually developed a myocardial phenotype under normal culture conditions over a prolonged culture period and heterogeneous populations were formed. In perspectives of clinical applications, this must be prevented for fair and consistent outcomes. Hence, the biomimetic 'niche' was constituted for hBM-MSCs by cultivating on a conventionally available extracellular matrix (ECM). Consequently, cells on ECM regained a spindle-shape morphology, increased in proliferation rate by two-fold and showed decreased expression of cardiac markers at both the mRNA and protein levels. In conclusion, the outcome indicates that progression of MSC senescence may occur via myocardial differentiation during in vitro polystyrene culture, and this can be overcome by employing appropriate ECM culture techniques.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/term.1754/abstract
DOI
10.1002/term.1754
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hyung(김재형)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146297
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