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First published online August 11, 2005
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2004-0236v1
24/1/186    most recent
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Submitted on September 9, 2004
Accepted on June 17, 2005

Original Article

Biological Activities Encoded by the Murine Mesenchymal Stem Cell Transcriptome Provide a Basis for Their Developmental Potential and Broad Therapeutic Efficacy

Donald G. Phinney 1*, Katy Hill 1, Charles Michelson 1, Maria DuTreil 1, Catherine Hughes 1, Sally Humphries 1, Robin Wilkinson 1, Melody Baddoo 1, Erica Bayly 1

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

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


  Abstract

We catalogued via serial analysis of gene expression (SAGE) the transcriptome of murine mesenchymal stem cells (MSCs) enriched from bone marrow by immunodepletion. Interrogation of this database, results of which are delineated in appended databases, revealed that immunodepleted murine MSCs (IDmMSCs) highly express transcripts encoding connective tissue proteins and factors modulating T cell proliferation, inflammation and bone turnover. Categorizing the transcriptome based on gene ontologies revealed the cells also expressed mRNAs encoding proteins that regulate mesoderm development or that are characteristic of determined mesenchymal cell lineages, thereby reflecting both their stem cell nature and differentiation potential. Additionally, IDmMSCs also expressed transcripts encoding proteins regulating angiogenesis, cell motility and communication, hematopoiesis, immunity and defense as well as neural activities. Immunostaining and FACS analysis revealed that expression of various regulatory proteins was restricted to distinct sub populations of IDmMSCs. Moreover, in some cases these proteins were absent or expressed at reduced levels in other murine MSC preparations or cell lines. Lastly, by comparing their transcriptome to that of 17 other murine cell types we also identified 43 IDmMSC-specific transcripts, the nature of which reflects their varied functions in bone and marrow. Collectively, these results demonstrate that IDmMSC express a diverse repertoire of regulatory proteins, which likely accounts for their demonstrated efficacy in treating a wide variety of diseases. The restricted expression pattern of these proteins within populations suggests that the cellular composition of marrow stroma and its associated functions are more complex than previously envisioned.

Key Words. SAGE, mesenchymal stem cells, bone marrow stromal cells




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