Clonal Analysis Reveals a Common Progenitor for Endothelial, Myeloid, and Lymphoid Precursors in Umbilical Cord Blood
Autor: | Sean P. Dineen, Nasrin Akbarloo, Jacquelyn Catanese, Luciene Borges, Rolf A. Brekken, Radbod Darabi, Rita C.R. Perlingeiro, Aline Lisie Ramos |
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Rok vydání: | 2010 |
Předmět: |
Pathology
medicine.medical_specialty Myeloid Physiology CD34 Antigens CD34 Mice SCID Biology Mice Antigens CD medicine Animals Humans Cell Lineage AC133 Antigen Progenitor cell Myeloid Progenitor Cells Glycoproteins Membrane Glycoproteins Stem Cells Hematopoietic Tissue Endothelial Cells Cell Differentiation Lymphoid Progenitor Cells Fetal Blood ADP-ribosyl Cyclase 1 Clone Cells Cell biology Endothelial stem cell medicine.anatomical_structure Cord blood Leukocyte Common Antigens Stem cell Peptides Cardiology and Cardiovascular Medicine Stem Cell Transplantation |
Zdroj: | Circulation Research. 107:1460-1469 |
ISSN: | 1524-4571 0009-7330 |
Popis: | Rationale: 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. Methods and 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. |
Databáze: | OpenAIRE |
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