title: Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood.
abstract: Umbilical cord blood (UCB) has been used as a potential source of various kinds of stem cells, including hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells (EPCs), for a variety of cell therapies. Recently, EPCs were introduced for restoring vascularization in ischemic tissues. An appropriate procedure for isolating EPCs from UCB is a key issue for improving therapeutic efficacy and eliminating the unexpected expansion of nonessential cells. Here we report a novel method for isolating EPCs from UCB by a combination of negative immunoselection and cell culture techniques. In addition, we divided EPCs into 2 subpopulations according to the aldehyde dehydrogenase (ALDH) activity. We found that EPCs with low ALDH activity (Alde-Low) possess a greater ability to proliferate and migrate compared to those with high ALDH activity (Alde-High). Moreover, hypoxia-inducible factor proteins are up-regulated and VEGF, CXCR4, and GLUT-1 mRNAs are increased in Alde-Low EPCs under hypoxic conditions, while the response was not significant in Alde-High EPCs. In fact, the introduction of Alde-Low EPCs significantly reduced tissue damage in ischemia in a mouse flap model. Thus, the introduction of Alde-Low EPCs may be a potential strategy for inducing rapid neovascularization and subsequent regeneration of ischemic tissues.
authors: Graduate School of Comprehensive Human Sciences, Department of Regenerative Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Masumi
authors: M
authors: Nagano
authors: Toshiharu
authors: T
authors: Yamashita
authors: Hiromi
authors: H
authors: Hamada
authors: Kinuko
authors: K
authors: Ohneda
authors: Ken-ichi
authors: K
authors: Kimura
authors: Tomoki
authors: T
authors: Nakagawa
authors: Masabumi
authors: M
authors: Shibuya
authors: Hiroyuki
authors: H
authors: Yoshikawa
authors: Osamu
authors: O
authors: Ohneda
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000502:physiology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000444:Aldehyde Dehydrogenase