The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice.
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.
Lee
Ryang Hwa
RH
Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, USA.
Seo
Min Jeong
MJ
Pulin
Andrey A
AA
Gregory
Carl A
CA
Ylostalo
Joni
J
Prockop
Darwin J
DJ
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D018952:Antigens, CD34; D000939:Epitopes; D039503:Integrin alpha6; D012795:Sialoglycoproteins; C001643:podocalyxin