Vascular potency of Sus scrofa bone marrow-derived mesenchymal stem cells: a progenitor source of medial but not endothelial cells.
Short-term thrombotic occlusion and compliance mismatch hamper clinical use of synthetic small-diameter tissue engineered vascular grafts. It is felt that preconditioning of the graft with intimal (endothelial) and medial (vascular smooth muscle) cells contributes to patency of the graft. Autologous, non-vessel-derived cells are preferred because of systemic vascular pathology and immunologic concerns. We tested in a porcine model whether cultured bone marrow-derived mononuclear cells, also referred to as mesenchymal stem cells (MSC), are a potential source of intimal or medial cells in vascular tissue engineering. We show that MSC cultured in endothelial medium do not gain an endothelial phenotype or functional characteristics, even after enrichment for CD31, culturing under flow, treatment with additional growth factors (vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2), or co-culture with microvascular endothelial cells (EC). On the other hand, we show that MSC cultured in MSC medium, but not in smooth muscle cell medium, show phenotypical and functional characteristics of vascular smooth muscle cells. We conclude that bone marrow-derived MSCs can be used as a bona fide source of medial, but not EC in small-diameter vascular tissue engineering.
Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands.
Nynke M S
NM
van den Akker
Felix F
FF
Kolk
Fabiënne
F
Jeukens
Sanne
S
Verbruggen
Mick
M
Gagliardi
Stefan
S
Dullens
Ingo
I
Heschel
Mark J
MJ
Post
Daniël G M
DG
Molin
Johannes
J
Waltenberger
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*
D009569:Nitric Oxide; D011464:Epoprostenol