Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood.
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.
Nagano
Masumi
M
Graduate School of Comprehensive Human Sciences, Department of Regenerative Medicine, University of Tsukuba, Tsukuba, Japan.
Yamashita
Toshiharu
T
Hamada
Hiromi
H
Ohneda
Kinuko
K
Kimura
Ken-ichi
K
Nakagawa
Tomoki
T
Shibuya
Masabumi
M
Yoshikawa
Hiroyuki
H
Ohneda
Osamu
O
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
D000444:Aldehyde Dehydrogenase