title: Improved survival, vascular differentiation and wound healing potential of stem cells co-cultured with endothelial cells.
abstract: In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34(+) cells), by co-culturing the stem cells in a 3D fibrin gel with CD34(+)-derived endothelial cells (ECs). ECs differentiated from CD34(+) cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34(+)-derived ECs on CD34(+) cells is mediated, at least in part, by bioactive factors released from ECs. This effect likely involves the secretion of novel cytokines, including interleukin-17 (IL-17) and interleukin-10 (IL-10), and the activation of the ERK 1/2 pathway in CD34(+) cells. We also show that the endothelial differentiation of CD34(+) cells in co-culture with CD34(+)-derived ECs is mediated by a combination of soluble and insoluble factors. The regenerative potential of this co-culture system was demonstrated in a chronic wound diabetic animal model. The co-transplantation of CD34(+) cells with CD34(+)-derived ECs improved the wound healing relatively to controls, by decreasing the inflammatory reaction and increasing the neovascularization of the wound.
authors.affiliation: Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Dora C S
authors.initials: DC
authors.lastname: Pedroso
authors.forename: Ana
authors.initials: A
authors.lastname: Tellechea
authors.forename: Liane
authors.initials: L
authors.lastname: Moura
authors.forename: Isabel
authors.initials: I
authors.lastname: Fidalgo-Carvalho
authors.forename: João
authors.initials: J
authors.lastname: Duarte
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
mesh_terms: D018952:Antigens, CD34; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation; D002470:Cell Survival; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology; D014945:Wound Healing
chemical_list: D018952:Antigens, CD34