Stem Cells
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First published online September 27, 2007
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Submitted on August 9, 2007
Accepted on September 21, 2007

TRANSLATIONAL AND CLINICAL RESEARCH: MESENCHYMAL STEM CELLS SERIES

Concise Review: Mesenchymal Stem/Multi-Potent Stromal Cells (MSCs): The State of Transdifferentiation and Modes of Tissue Repair - Current Views

Donald G. Phinney 1* and Darwin J. Prockop 1

1 Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA

* To whom correspondence should be addressed. E-mail: dphinne{at}tulane.edu.


  Abstract

Mesenchymal stem cells or multi-potent stromal cells (MSCs) isolated from the bone marrow of adult organisms were initially characterized as plastic adherent, fibroblastoid cells with the capacity to generate heterotopic osseous tissue when transplanted in vivo. In recent years MSCs or MSC-like cells have been shown to reside within the connective tissue of most organs and their surface phenotype has been well-described. A large number of reports have also indicated that the cells possess the capacity to trans-differentiate into epithelial cells and lineages derived from the neuro-ectoderm. The broad developmental plasticity of MSCs was originally thought to contribute to their demonstrated efficacy in a wide variety of experimental animal models of disease as well as in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for transdifferentiation in tissue repair. Herein, we critically evaluate the literature describing the plasticity of MSCs and offer insight into how the molecular and functional heterogeneity of this cell population, which reflects the complexity of marrow stroma as an organ system, may confound interpretation of their transdifferentiation potential. Additionally, we argue that this heterogeneity also provides a basis for the broad therapeutic efficacy of MSCs.

Key Words. Mesenchymal stem cells, marrow stromal cells, marrow stromal stem cells, cellular therapy, transdifferentiation




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