Abstract
Cell therapy has emerged as a promising strategy for treating neurological diseases such as stroke, spinal cord injury, and various neurodegenerative diseases, but both embryonic neural stem cells and human induced Pluripotent Stem Cell- (iPSC-) derived neural stem cells have major limitations which restrict their broad use in these diseases. We want to find a one-step induction method to transdifferentiate the more easily accessible Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) into neural stem/progenitor cells suitable for cell therapy purposes. In this study, UC-MSCs were induced to form neurospheres under a serum-free suspension culture with Epidermal Growth Factor- (EGF-) and basic Fibroblast Growth Factor- (bFGF-) containing medium within 12 hours. These MSC-derived neurospheres can self-renew to form secondary neurospheres and can be readily induced to become neurons and glial cells. Real-time PCR showed significantly upregulated expression of multiple stemness and neurogenic genes after induction. RNA transcriptional profiling study showed that UC-MSC-derived neurospheres had a unique transcriptional profile of their own, with features of both UC-MSCs and neural stem cells. RayBio human growth factor cytokine array analysis showed significantly upregulated expression levels of multiple neurogenic and angiogenic growth factors, skewing toward a neural stem cell phenotype. Thus, we believe that these UC-MSC-derived neurospheres have amenable features of both MSCs and neural stem/progenitor cells and have great potential in future stem cell transplantation clinical trials targeting neurological disorders.
Highlights
Mesenchymal stem cells are adult stem cells derived from mesenchymal tissues
mesenchymal stem cells (MSCs) have been shown to be efficiently induced to form neurons under certain induction methods in ex vivo experiments [15,16,17,18,19], when these cells are infused in vivo when they need in vivo microenvironment cues to transdifferentiate, they do not perform so well [20, 21]
We reported for the first time that UCMSCs can be efficiently induced to form neurosphere-like cells under standard culture conditions used for neurospheres (DMEM/F12, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), N2, and B27) within 12 hours
Summary
Human MSCs can be obtained from various sources such as bone marrow, umbilical cord, cord blood, adipose tissue, even the dental pulp [1,2,3]. They have great advantages of easy accessibility, easy manipulation, and low HLA typing restriction, combined with their promising features of self-renewal and multipotency, making them the most commonly used adult stem cells in regenerative medicine. For the treatment of neurological diseases, it would be clinically more relevant and efficient if we could use neural stem cells in these trials. It would be ideal to find a cell source which combines the strength of both MSCs and neural stem cells, having both of their desirable features in one cell source
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