BACKGROUND: Bone marrow-derived circulating CD34(+) progenitor cells participate in remodeling and repair of the vasculature. Coexpression of the kinase-insert domain-containing receptor (KDR) has been proposed to identify the regenerative capacity. Recently, we provided evidence that the major fraction of circulating CD34(+) /KDR(+) cells is not mobilized from bone marrow, but is generated at sites of vascular injury through interaction with platelets. OBJECTIVES: To determine the relationship between platelet activation, the recruitment of naïve CD34(+) cells and the generation of CD34(+) /KDR(+) progenitor cells in a broad range of (patho)physiologic conditions, a detailed meta-regression analysis was conducted. METHODS/ RESULTS: Twenty-eight conditions were found in which the numbers of CD34(+) and/or CD34(+) /KDR(+) cells and the levels of soluble P-selectin, as a marker for in vivo platelet activation, were documented. To combine heterogeneous data from 214 selected articles, results were standardized to a uniform scale by calculating standardized mean differences (SMDs) obtained from patient and control cohorts. Subsequently, a random-effects meta-regression analysis was performed on pooled SMDs. CONCLUSIONS: Our systemic survey supports a model in which activated platelets are a determinant for mobilization of CD34(+) cells from the bone marrow and the generation of CD34(+) /KDR(+) cells in the circulation.
BACKGROUND: Bone marrow-derived circulating CD34(+) progenitor cells participate in remodeling and repair of the vasculature. Coexpression of the kinase-insert domain-containing receptor (KDR) has been proposed to identify the regenerative capacity. Recently, we provided evidence that the major fraction of circulating CD34(+) /KDR(+) cells is not mobilized from bone marrow, but is generated at sites of vascular injury through interaction with platelets. OBJECTIVES: To determine the relationship between platelet activation, the recruitment of naïve CD34(+) cells and the generation of CD34(+) /KDR(+) progenitor cells in a broad range of (patho)physiologic conditions, a detailed meta-regression analysis was conducted. METHODS/ RESULTS: Twenty-eight conditions were found in which the numbers of CD34(+) and/or CD34(+) /KDR(+) cells and the levels of soluble P-selectin, as a marker for in vivo platelet activation, were documented. To combine heterogeneous data from 214 selected articles, results were standardized to a uniform scale by calculating standardized mean differences (SMDs) obtained from patient and control cohorts. Subsequently, a random-effects meta-regression analysis was performed on pooled SMDs. CONCLUSIONS: Our systemic survey supports a model in which activated platelets are a determinant for mobilization of CD34(+) cells from the bone marrow and the generation of CD34(+) /KDR(+) cells in the circulation.