Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood.
BACKGROUND
several studies demonstrate that hematopoietic tissues are a source of endothelial progenitor cells, which contribute to newly formed blood vessels during tissue repair in adults. However, it is not clear which cell type in these hematopoietic tissues gives rise to endothelial progenitor cells.


OBJECTIVE
to identity the origin of endothelial progenitors within the hematopoietic hierarchy and to assess their in vivo revascularization potential.


RESULTS
using a single-cell sorting approach and in vitro multilineage differentiation assays, here we show that individual CD34(+)CD45(+)CD133(+)CD38(+) cells from cord blood uniquely have the ability to differentiate into T- and B-lymphoid, myeloid, and endothelial cells. The latter were characterized by the expression of VE-cadherin, KDR, von Willebrand factor, endothelial nitric oxide synthase, the lack of CD45, CD133, and c-fms (colony stimulating factor-1 receptor). Unexpectedly when transplanted into hindlimb ischemic NOD-scid IL2Rγ(null) mice, freshly isolated CD34(+)CD45(+)CD133(+)CD38(+) cells maintained their hematopoietic identity and were rarely found to integrate into host blood vessels. Nevertheless, they significantly improved perfusion, most likely through a paracrine mechanism. On the other hand, CD34(+)CD45(+)CD133(+)CD38(+) cells differentiated in vitro into endothelial cells were able to form vessels in vivo in both Matrigel plug and hindlimb ischemia transplantation assays.


CONCLUSIONS
these findings indicate that the CD34(+)CD45(+)CD133(+)CD38(+) cell fraction contains a common progenitor for the hematopoietic and vascular lineages and may represent a valuable cell source for therapeutic applications.
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, USA.
Aline Lisie
AL
Ramos
Radbod
R
Darabi
Nasrin
N
Akbarloo
Luciene
L
Borges
Jacquelyn
J
Catanese
Sean P
SP
Dineen
Rolf A
RA
Brekken
Rita C R
RC
Perlingeiro
D000071916:AC133 Antigen; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34; D002454:Cell Differentiation; D019070:Cell Lineage; D002999:Clone Cells / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology; D005312:Fetal Blood / Q000166:cytology*; D006023:Glycoproteins; D006801:Humans; D017493:Leukocyte Common Antigens; D054503:Lymphoid Progenitor Cells / Q000166:cytology; D008562:Membrane Glycoproteins; D051379:Mice; D016513:Mice, SCID; D023461:Myeloid Progenitor Cells / Q000166:cytology; D010455:Peptides; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1