Augmentation of neovascularization [corrected] in hindlimb ischemia by combined transplantation of human embryonic stem cells-derived endothelial and mural cells.
BACKGROUND
We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration.


RESULTS
After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity.


CONCLUSIONS
Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia.
Yamahara
Kenichi
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sone
Masakatsu
M
Itoh
Hiroshi
H
Yamashita
Jun K
JK
Yurugi-Kobayashi
Takami
T
Homma
Koichiro
K
Chao
Ting-Hsing
TH
Miyashita
Kazutoshi
K
Park
Kwijun
K
Oyamada
Naofumi
N
Sawada
Naoya
N
Taura
Daisuke
D
Fukunaga
Yasutomo
Y
Tamura
Naohisa
N
Nakao
Kazuwa
K
D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D042783:Endothelial Cells / Q000637:transplantation; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D018919:Neovascularization, Physiologic; D012039:Regional Blood Flow; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous