Endothelial differentiation of hematopoietic stem and progenitor cells from patients with multiple myeloma.
OBJECTIVE
Vasculogenesis is a physiologic process typical of fetal development in which new blood vessels develop from undifferentiated precursors (or angioblasts). In tumors, near angiogenesis, vasculogenesis contributes to the formation of the microvascular plexus that is important for diffusion. Here, we show that hematopoietic stem and progenitor cells (HSPC) of multiple myeloma (MM) patients are able to differentiate into cells with endothelial phenotype on exposure to angiogenic cytokines.


METHODS
Circulating HSPCs were purified with an anti-CD133 antibody from patients with newly diagnosed MM before autologous transplantation and exposed to vascular endothelial growth factor (VEGF), fibroblast growth factor-2 and insulin-like growth factor in a 3-week culture.


RESULTS
HSPCs gradually lost CD133 expression and acquired VEGF receptor-2, factor VIII-related antigen, and vascular endothelial-cadherin expression. The expression pattern overlapped with paired MM endothelial cells (MMEC). During culture, cells adhered to fibronectin, spread, and acquired an endothelial cell shape. Differentiated HSPCs also became capillarogenic in the Matrigel assay with maximal activity at the third week of culture. Bone marrow biopsies revealed HSPCs inside the neovessel wall in patients with MM but not in those with monoclonal gammopathy of undetermined significance.


CONCLUSIONS
In patients with MM, but not in those with monoclonal gammopathy of undetermined significance, HSPCs contribute to the neovessel wall building together with MMECs. Therefore, besides angiogenesis, HSPC-linked vasculogenesis contributes to neovascularization in MM patients. Tentatively, we hypothesize that in HSPC cultures a multipotent cell population expressing low VEGF receptor-2 levels corresponds to the endothelial progenitor cell precursor and seems to be the MMEC precursor.
Ria
Roberto
R
Department of Internal Medicine, University of Bari Medical School, Bari, Italy.
Piccoli
Claudia
C
Cirulli
Teresa
T
Falzetti
Franca
F
Mangialardi
Giuseppe
G
Guidolin
Diego
D
Tabilio
Antonio
A
Di Renzo
Nicola
N
Guarini
Attilio
A
Ribatti
Domenico
D
Dammacco
Franco
F
Vacca
Angelo
A
D053687:Adult Stem Cells / Q000473:pathology / Q000502:physiology; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D010641:Phenotype