The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice

Blood. 2009 Jan 22;113(4):816-26. doi: 10.1182/blood-2007-12-128702. Epub 2008 Sep 25.

Abstract

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), alpha6-integrin (CD49f), alpha4-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. PODXL(hi)/CD49f(hi) MSCs were more clonogenic and differentiated more efficiently than PODXL(lo)/CD49f(lo) cells. Inhibition of expression of PODXL with RNA interference caused aggregation of the cells. Furthermore, PODXL(hi)/CD49f(hi) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Cell Movement*
  • Cells, Cultured
  • Epitopes / immunology
  • Gene Expression Regulation
  • Humans
  • Integrin alpha6 / genetics
  • Integrin alpha6 / metabolism*
  • Kidney / cytology
  • Kidney / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism*
  • Time Factors

Substances

  • Antigens, CD34
  • Epitopes
  • Integrin alpha6
  • Sialoglycoproteins
  • podocalyxin