Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood

Aline Lisie Ramos, Radbod Darabi, Nasrin Akbarloo, Luciene Borges, Jacquelyn Catanese, Sean P. Dineen, Rolf A. Brekken, Rita C R Perlingeiro

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)1460-1469
Number of pages10
JournalCirculation Research
Volume107
Issue number12
DOIs
StatePublished - Dec 10 2010

Fingerprint

Lymphoid Progenitor Cells
Myeloid Progenitor Cells
Fetal Blood
Blood Vessels
Hindlimb
Endothelial Cells
Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Nitric Oxide Synthase Type III
von Willebrand Factor
Myeloid Cells
Ischemia
Perfusion
Transplantation
Lymphocytes

Keywords

  • clonal analyses
  • cord blood
  • endothelial progenitors
  • engraftment
  • ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ramos, A. L., Darabi, R., Akbarloo, N., Borges, L., Catanese, J., Dineen, S. P., ... Perlingeiro, R. C. R. (2010). Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood. Circulation Research, 107(12), 1460-1469. https://doi.org/10.1161/CIRCRESAHA.110.223669

Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood. / Ramos, Aline Lisie; Darabi, Radbod; Akbarloo, Nasrin; Borges, Luciene; Catanese, Jacquelyn; Dineen, Sean P.; Brekken, Rolf A.; Perlingeiro, Rita C R.

In: Circulation Research, Vol. 107, No. 12, 10.12.2010, p. 1460-1469.

Research output: Contribution to journalArticle

Ramos, AL, Darabi, R, Akbarloo, N, Borges, L, Catanese, J, Dineen, SP, Brekken, RA & Perlingeiro, RCR 2010, 'Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood', Circulation Research, vol. 107, no. 12, pp. 1460-1469. https://doi.org/10.1161/CIRCRESAHA.110.223669
Ramos, Aline Lisie ; Darabi, Radbod ; Akbarloo, Nasrin ; Borges, Luciene ; Catanese, Jacquelyn ; Dineen, Sean P. ; Brekken, Rolf A. ; Perlingeiro, Rita C R. / Clonal analysis reveals a common progenitor for endothelial, myeloid, and lymphoid precursors in umbilical cord blood. In: Circulation Research. 2010 ; Vol. 107, No. 12. pp. 1460-1469.
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AU - Catanese, Jacquelyn

AU - Dineen, Sean P.

AU - Brekken, Rolf A.

AU - Perlingeiro, Rita C R

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N2 - 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 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.

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