Myoendothelial differentiation of human umbilical cord blood-derived stem cells in ischemic limb tissues.
Human umbilical cord blood (UCB) contains high numbers of endothelial progenitors cells (EPCs) characterized by coexpression of CD34 and CD133 markers. Prior studies have shown that CD34+/CD133+ EPCs from the cord or peripheral blood (PB) can give rise to endothelial cells and induce angiogenesis in ischemic tissues. In the present study, it is shown that freshly isolated human cord blood CD34+ cells injected into ischemic adductor muscles gave rise to endothelial and, unexpectedly, to skeletal muscle cells in mice. In fact, the treated limbs exhibited enhanced arteriole length density and regenerating muscle fiber density. Under similar experimental conditions, CD34- cells did not enhance the formation of new arterioles and regenerating muscle fibers. In nonischemic limbs CD34+ cells increased arteriole length density but did not promote formation of new muscle fibers. Endothelial and myogenic differentiation ability was maintained in CD34+ cells after ex vivo expansion. Myogenic conversion of human cord blood CD34+ cells was also observed in vitro by coculture onto mouse myoblasts. These results show that human cord blood CD34+ cells differentiate into endothelial and skeletal muscle cells, thus providing an indication of human EPCs plasticity. The full text of this article is available online at http://www.circresaha.org.
Pesce
Maurizio
M
Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico Monzino, IRCCS, Milan, Italy. m.pesce@idi.it
Orlandi
Alessia
A
Iachininoto
Maria Grazia
MG
Straino
Stefania
S
Torella
Anna Rita
AR
Rizzuti
Vania
V
Pompilio
Giulio
G
Bonanno
Giuseppina
G
Scambia
Giovanni
G
Capogrossi
Maurizio C
MC
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood / Q000737:chemistry / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007511:Ischemia / Q000628:therapy; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D012038:Regeneration; D014183:Transplantation, Heterologous
D018952:Antigens, CD34