Identification of human circulating progenitors with angiogenic potential

by Alexey Bersenev on October 18, 2011 · 0 comments

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There is an ongoing debate about identity and function of human circulating progenitor cells (CPC). Phenotypic identity of circulating endothelial progenitor cells (EPC), proposed more than a decade ago, was challenged in later reports:

While thousands of articles have been published since 2000 using some combination of CD34, CD133, or KDR with or without other markers such as CD31 and Tie 2 (in mice) to identify circulating EPCs, and many of the articles have reported statistically significant correlations between the blood concentration of the selected putative EPC subset and a disease state, few had attempted to formally compare the functional properties of isolated human circulating CD34+KDR+CD133+ cells in hematopoietic and endothelial assays.

So, variety of circulating progenitor cell subsets were described in the last few years. However, debates still persist due to inaccurate flow cytometric assessment (lack of controls) or lack of functional validation:

Confusion around the function of, EPCs, circulating endothelial progenitors (CEPs), and CPCs in vascular repair and regeneration at homeostasis or in response to injury or disease is linked to lack of consensus regarding quantitative measures to isolate each cell type using in vitro colony assays, immunomagnetic separation (IMS), or conventional flow cytometry approaches.

Use of the term CPC, without functional validation of the cell types comprising this fraction has not been helpful in understanding the mechanisms of cellular action purported to emerge from these flow cytometry “events.”

The study, published in Cytometry a year ago, has clarified some issues:

.. we now identify the circulating pool of CD34+CD45dim cells representing functional circulating hematopoietic stem and progenitor cells (CHSPCs) that can be separated on the basis of AC133 expression and report that the AC133+ subset of the CHSPCs enhances the growth of tumor blood vessels in vivo in immunodeficient mice.

This particular CHSPC subset was enriched in cells displaying a variety of myeloid cell surface antigens in addition to displaying in vitro and in vivo HSPC functions. This subset did not display any vasculogenic ability in vivo when examined for the presence of human endothelium within the explanted human tumors within the immunodeficient mice.

So, among circulating progenitor cells we should recognize populations with hematopoietic, angiogenic, vasculogenic and mixed potential, sharing different combinations of hematopoietic and endothelial markers.

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