Human CD34 ⁺ /KDR ⁺ Cells Are Generated From Circulating CD34 ⁺ Cells After Immobilization on Activated Platelets

Abstract

Objective-The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34ϩ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34 ϩ cells co-express KDR. Therefore, we studied whether CD34

Expression of Junctional Adhesion Molecule-C on the Surface of Platelets Supports Adhesion, but not Differentiation, of Human CD34⁺ Cells <i>in Vitro</i>

“…Increasing evidence the last years has proven that bone marrow-derived CD34 + cells are mobilised after acute ischemia supporting among others angiogenesis, neurogenesis after ischemic stroke, myocardial healing after myocardial infarction and vascular regeneration after vascular injury [28][29][30] . Transplantation of human CD34 + cells is an established routine therapy after bone marrow irradiation or myeloablative anticancer chemotherapy in patients with different forms of cancer including multiple myeloma, lymphoma, acute leukemia and breast cancer [6,31]. The last 6 years accumulating evidence supported the usage of human CD34 + cells in patients with ischemic or dilative cardiomyopathy and peripheral vascular disease, although the first clinical results did not reach the high expectations of the scientific community .…”

“…Platelets are crucially involved in progenitor cell recruitment on vascular wall and differentiation into endothelial cells or macrophages [1][2][3][4][5][6]. Profound impairment in neovascularization was reported in thrombocyto-154 penic mice highlighting the essential role of platelets in mobilization and incorporation of hemangiocytes into ischemic limbs in vivo [2].…”

Circulating progenitor cells are increased in newly diagnosed untreated hypertensive patients with arterial stiffening but normal carotid intima-media thickness

“…2 Additionally, most, if not all, circulating CD34 + cells have the ability to rapidly upregulate KDR expression once activated by peripheral stimuli, becoming EPCs at sites of vascular injury. 9 Moreover, CD133 + cells are mainly a subgroup of CD34 + cells, and a close correlation between the expression of these two antigens exists, suggesting that the determination of CD133 expression on CD34 + cells (CD34 + / CD133 + phenotype) would not provide much additional information. 6 That may explain data from previous studies reporting that the CD34 + cell count is more closely linked to CV risk than double-or triple-positive cells.…”

“…2 Indeed, circulating CD34 + cells can rapidly express vascular endothelial growth factor receptor-2 also known as kinase insert domain receptor (KDR) on their surface, becoming EPCs at the site of vascular injury, reflecting the plasticity of these cells and their capacity to respond to vascular stimuli. 9 The therapeutic administration of autologous EPCs augments neovascularization in vivo 10 and promotes postinfarction remodeling. 11 To heal the vascular endothelium and to survive in necrotic and ischemic tissues, EPCs are equipped with an efficacious antioxidant system.…”

Close Encounters of the Third Kind

“…2 By using an ex vivo flow model, the authors show that activated platelets favor the homing of CD34 ϩ cells to sites of vascular injury and that, on cell immobilization, KDR is rapidly translocated from an endosomal compartment to the cell surface. Presumably, PCs shed afterward to "carry the message" into the circulation.…”