Bone marrow–derived CMPs and GMPs represent highly functional proangiogenic cells: implications for ischemic cardiovascular disease

AK Wara, K Croce, SY Foo, X Sun, B Icli… - Blood, The Journal …, 2011 - ashpublications.org
AK Wara, K Croce, SY Foo, X Sun, B Icli, Y Tesmenitsky, F Esen, A Rosenzweig
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
Clinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated
modest improvements of function and/or perfusion of ischemic myocardium or skeletal
muscle. Because the identities of these PACs and their functional ability to promote
neovascularization remain poorly understood, it is possible that a subset of robust PACs
exists but is obscured by the heterogeneous nature of this cell population. Herein, we found
that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) …
Abstract
Clinical studies using bone marrow–derived proangiogenic cells (PACs) have demonstrated modest improvements of function and/or perfusion of ischemic myocardium or skeletal muscle. Because the identities of these PACs and their functional ability to promote neovascularization remain poorly understood, it is possible that a subset of robust PACs exists but is obscured by the heterogeneous nature of this cell population. Herein, we found that common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) preferentially differentiate into PACs compared with megakaryocyte-erythrocyte progenitors, hematopoietic stem cells, and common lymphoid progenitors. In vivo hindlimb ischemia studies and Matrigel plug assays verified the enhanced neovascularization properties uniquely associated with PACs derived from CMPs and GMPs. Taken together, these observations identify CMPs and GMPs as key bone marrow progenitors for optimal PAC function in vitro and in vivo and provide a foundation for novel therapeutic approaches to modulate angiogenesis.
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