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 Blood, 22 January 2009, Vol. 113, No. 4, pp. 816-826.
Prepublished online as a Blood First Edition Paper on September 25, 2008; DOI 10.1182/blood-2007-12-128702.

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HEMATOPOIESIS AND STEM CELLS

The CD34-like protein PODXL and {alpha}6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice

Ryang Hwa Lee1,*, Min Jeong Seo1,*, Andrey A. Pulin1, Carl A. Gregory1, Joni Ylostalo1, and Darwin J. Prockop1

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

We screened for surface proteins expressed only by the early progenitor cells present in low-passage, low-density cultures of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent stromal cells (MSCs). Six proteins were identified that were selectively expressed in the early progenitors: podocalyxin-like protein (PODXL), {alpha}6-integrin (CD49f), {alpha}4-integrin (CD49d), c-Met, CXCR4, and CX3CR1. All were previously shown to be involved in cell trafficking or tumor progression. Antibodies to CD49f and PODXL, a sialomucin in the CD34 family, were the most robust for FACScan assays. PODXLhi/CD49fhi MSCs were more clonogenic and differentiated more efficiently than PODXLlo/CD49flo cells. Inhibition of expression of PODXL with RNA interference caused aggregation of the cells. Furthermore, PODXLhi/CD49fhi MSCs were less prone to produce lethal pulmonary emboli, and larger numbers were recovered in heart and kidney after intravenous infusion into mice with myocardial infarcts.


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