The developmental basis of mesenchymal stem/stromal cells (MSCs)

Guojun Sheng

Mesenchymal Stem/Stromal Cells (MSCs) define a population of progenitor cells capable of giving rises to at least three mesodermal lineages in vitro, the chondrocytes, osteoblasts and adipocytes. The validity of MSCs in vivo has been questioned because their existence, either as a homogeneous progenitor cell population or as a stem cell lineage, has been difficult to prove. The wide use of primary MSCs in regenerative and therapeutic applications raises ethical and regulatory concerns in many countries. In contrast to hematopoietic stem cells, a parallel concept which carries an embryological emphasis from its outset, MSCs have attracted little interest among developmental biologists and the embryological basis for their existence, or lack thereof, has not been carefully evaluated. This article provides a brief, embryological overview of these three mesoderm cell lineages and offers a framework of ontological rationales for the potential existence of MSCs in vivo. Emphasis is given to the common somatic lateral plate mesoderm origin of the majority of body's adipose and skeletal tissues and of the major sources used for MSC derivation clinically. Support for the MSC hypothesis also comes from a large body of molecular and lineage analysis data in vivo. It is concluded that despite the lack of a definitive proof, the MSC concept has a firm embryological basis and that advances in MSC research can be facilitated by achieving a better integration with developmental biology.