title: Fast-proliferating adipose tissue mesenchymal-stromal-like cells for therapy.
abstract: Human mesenchymal stromal cells, whether from the bone marrow or adipose tissue (hASCs), are promising cell therapy agents. However, generation of abundant cells for therapy remains to be a challenge, due to the need of lengthy expansion and the risk of accumulating genomic defects during the process. We show that hASCs can be easily induced to a reversible fast-proliferating phenotype (FP-ASCs) that allows rapid generation of a clinically useful quantity of cells in <2 weeks of culture. Expanded FP-ASCs retain their finite expansion capacity and pluripotent properties. Despite the high proliferation rate, FP-ASCs show genomic stability by array-comparative genomic hybridization, and did not generate tumors when implanted for a long time in an SCID mouse model. Comparative analysis of gene expression patterns revealed a set of genes that can be used to characterize FP-ASCs and distinguish them from hASCs. As potential candidate therapeutic agents, FP-ASCs displayed high vasculogenic capacity in Matrigel assays. Moreover, application of hASCs and FP-ASCs in a fibrin scaffold over a myocardium infarct model in SCID mice showed that both cell types can differentiate to endothelial and myocardium lineages, although FP-ASCs were more potent angiogenesis inducers than hASCs, at promoting myocardium revascularization.
authors.affiliation: 1 Human DNA Variability Department, GENYO-Centre for Genomic and Oncological Research (Pfizer/University of Granada/Andalusian Regional Government) , PTS Granada, Granada, Spain .
authors.forename: Elisabet
authors.initials: E
authors.lastname: Aguilar
authors.forename: Julio Rodriguez
authors.initials: JR
authors.lastname: Bagó
authors.forename: Carol
authors.initials: C
authors.lastname: Soler-Botija
authors.forename: Maria
authors.initials: M
authors.lastname: Alieva
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Rigola
authors.forename: Carme
authors.initials: C
authors.lastname: Fuster
authors.forename: Olaia F
authors.initials: OF
authors.lastname: Vila
authors.forename: Nuria
authors.initials: N
authors.lastname: Rubio
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Blanco
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D064593:Heterografts; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*