title: The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice.
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.
authors.affiliation: Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Ryang Hwa
authors.initials: RH
authors.lastname: Lee
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Seo
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Pulin
authors.forename: Carl A
authors.initials: CA
authors.lastname: Gregory
authors.forename: Joni
authors.initials: J
authors.lastname: Ylostalo
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
mesh_terms: 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
chemical_list: D018952:Antigens, CD34; D000939:Epitopes; D039503:Integrin alpha6; D012795:Sialoglycoproteins; C001643:podocalyxin