Abstract

Mesenchymal stem cells (MSCs) are heterogeneous multipotent stem cells that are involved in the development of mesenchyme-derived evolving structures and organs during ontogeny. In the adult organism, reservoirs of MSCs can be found in almost all tissues where MSCs contribute to the maintenance of organ integrity. The use of these different MSCs for cell-based therapies has been extensively studied over the past years, which highlights the use of MSCs as a promising option for the treatment of various diseases including autoimmune and cardiovascular disorders. However, the proportion of MSCs contained in primary isolates of adult tissue biopsies is rather low and, thus, vigorous ex vivo expansion is needed especially for therapies that may require extensive and repetitive cell substitution. Therefore, more easily and accessible sources of MSCs are needed. This review summarizes the current knowledge of the different strategies to generate human MSCs in vitro as an alternative method for their applications in regenerative therapy.

Highlights

  • Among the adult stem cells, Mesenchymal stem cells (MSCs) are supposed to be the most promising stem cell type for cell-based therapies [1,2,3,4]

  • The first reports on MSCs generated from pluripotent stem cells were performed with pluripotent embryonic stem cells before induced pluripotent stem cells (iPSCs) came into focus

  • Concerning the proliferative and regenerative potency of generated MSC, iPSC-derived MSC may be superior to somatic cell-derived MSC because MSCs differentiated from iPSCs might be closer to fetal MSCs, since pluripotent stem cells represent the early time point in development

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Summary

Introduction

Among the adult stem cells, MSCs are supposed to be the most promising stem cell type for cell-based therapies [1,2,3,4]. MSC can either act directly by homing to particular anatomical sites after transplantation and differentiating into specific cell types to locally restore the damaged tissue. MSCs lack immunogenicity and possess the ability to perform immunomodulatory functions [15, 16]. These unique properties have promoted numerous applications of MSCs which currently undergo hundreds of clinical trials (http://www.clinicaltrials.gov) for disease treatments including graft versus host disease, chronic obstructive pulmonary disease, Crohn’s disease, or even multiple sclerosis [17,18,19,20]. To circumvent many of these issues, alternative methods to generate therapeutically sufficient numbers of MSCs in vitro were established. This review will focus on the different methods to generate therapeutically active MSCs in vitro

Patient-Specific MSCs
Human Embryonic Stem Cell-Derived MSCs
Direct Conversion of MSCs from Somatic Cells
The Pros and Cons
Findings
Conclusion

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