Open AccessStability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy
Author(s) -
Binato R.,
de Souza Fernandez T.,
LazzarottoSilva C.,
Du Rocher B.,
Mencalha A.,
Pizzatti L.,
Bouzas L. F.,
Abdelhay E.
Publication year - 2013
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12002
Subject(s) - mesenchymal stem cell , biology , stem cell , microbiology and biotechnology , in vitro , cell therapy , cell , epigenetics , cell culture , cellular differentiation , clinical uses of mesenchymal stem cells , immunology , adult stem cell , gene , genetics , endothelial stem cell
Ex vivo expansion and manipulation of human mesenchymal stem cells are important approaches to immunoregulatory and regenerative cell therapies. Although these cells show great potential for use, issues relating to their overall nature emerge as problems in the field. The need for extensive cell quantity amplification in vitro to obtain sufficient cell numbers for use, poses a risk of accumulating genetic and epigenetic abnormalities that could lead to sporadic malignant cell transformation. In this study, we have examined human mesenchymal stem cells derived from bone marrow, over extended culture time, using cytogenetic analyses, mixed lymphocyte reactions, proteomics and gene expression assays to determine whether the cultures would retain their potential for use in subsequent passages. Results indicate that in vitro cultures of these cells demonstrated chromosome variability after passage 4, but their immunomodulatory functions and differentiation capacity were maintained. At the molecular level, changes were observed from passage 5 on, indicating initiation of differentiation. Together, these results lead to the hypothesis that human mesenchymal stem cells cultures can be used successfully in cell therapy up to passage 4. However, use of cells from higher passages would have to be analysed case by case.