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Blood, 15 July 2008, Vol. 112, No. 2, pp. 217-218.
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HEMATOPOIESIS & STEM CELLS
Comment on Ng et al, page 295
A new window on MSCs
Ernestina Schipani
HARVARD MEDICAL SCHOOL
The study from Ng et al opens a new window on MSCs by testing the feasibility of a global gene expression–profiling approach to gain insights into the molecular mechanisms that regulate this population.
The article by Ng and colleagues in this issue of Blood opens a new window on the identification of molecular mechanisms that regulate the fate of mesenchymal stem cells in vitro. In the early 1970s, Friedenstein and colleagues were the first to report the presence of fibroblastoid cells that could be flushed out from adult bone marrow, form colonies on plastic, and, when transplanted subcutaneously with appropriate carriers, give origin to ossicles in which the hematopoietic component had originated from the host.1 In other words, Friedenstein provided the first evidence of the existence in the bone marrow of what later on would have been called mesenchymal stem cells (MSCs). Over the years, it has become progressively clear that such cells, which can differentiate into a variety of mesenchymal lineages such as osteoblasts, chondrocytes, and adipocytes, are not an exclusive feature of the bone marrow, but can also be isolated from other adult organs and tissues including fat. A large number of studies have provided evidence in support of MSC plasticity, their potential use for tissue engineering purposes, their extraordinary immunomodulatory properties, and their ability to be recruited at sites of injury, where they would contribute a natural in vivo system for tissue repair through cell fusion, production of specific cytokines, or even differentiation into the appropriate cell phenotype.2–4 A characterization of both their cell surface–specific antigens and their anatomical location in vivo has been pursued as well.4,5
However, despite this impressive body of work, numerous questions related to the developmental origin of these cells, their proposed pluripotency, and their participation in the physiological processes of bone modeling and remodeling in vivo remain largely unanswered. More importantly, a detailed and systematic analysis of the complex network of signaling pathways, which very likely regulate MSC ability to self-renew, proliferate, and eventually differentiate, has just begun. The identification of this network is critically important in reaching a deeper understanding of the rules that govern the size of the MCS pool both in vivo and in vitro, which would then ultimately allow for appropriate pharmaco-logic or genetic intervention.
Ng and colleagues use a global gene-expression profiling approach and compare the transcriptomes of bone marrow MSCs with the transcriptome of terminally differentiated adipocytes, osteocytes, and chondrocytes derived from these same cells. This novel and global approach allows the authors to identify markers of both MSCs and their progeny, as well as signaling pathways involved in their growth and differentiation, some of which have been previously reported. All in all, the authors provide solid and clear evidence supporting the feasibility of a global approach to gain insights into the molecular mechanisms that regulate both the size and the differentiation potential of the MSC pool. Whether this knowledge can be applied to the in vivo setting, however, is an open question.
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests. 
REFERENCES
- Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues: cloning in vitro and retransplantation in vivo. Transplantation. 1974;17:331–340.[Medline]
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- Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–1084.[CrossRef][Medline]
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- Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: characterization, differentiation and application in cell and gene therapy. J Cell Mol Med. 2004;8:301–316.[Medline]
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- Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ. Mesenchymal stem cells. Arch Med Res. 2003;34:565–571.[CrossRef][Medline]
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- Sacchetti B, Funari A, Michienzi S, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324–336.[CrossRef][Medline]
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Related Article in Blood Online:
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PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages
- Felicia Ng, Shayne Boucher, Susie Koh, Konduru S. R. Sastry, Lucas Chase, Uma Lakshmipathy, Cleo Choong, Zheng Yang, Mohan C. Vemuri, Mahendra S. Rao, and Vivek Tanavde
Blood 2008 112: 295-307.
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