title: A cautionary tale for autologous vascular tissue engineering: impact of human demographics on the ability of adipose-derived mesenchymal stem cells to recruit and differentiate into smooth muscle cells.
abstract: Autologous tissue-engineered blood vessels (TEBVs) generated using adult stem cells have shown promising results, but many preclinical evaluations do not test the efficacy of stem cells from patient populations likely to need therapy (i.e., elderly and diabetic humans). Two critical functions of these cells will be (i) secreting factors that induce the migration of host cells into the graft and (ii) differentiating into functional vascular cells themselves. The purpose of this study was to analyze whether adipose-derived mesenchymal stem cells (AD-MSCs) sourced from diabetic and elderly patients have a reduced ability to promote human smooth muscle cell (SMC) migration and differentiation potential toward SMCs, two important processes in stem cell-based tissue engineering of vascular grafts. SMC monolayers were disrupted in vitro by a scratch wound and were induced to close the wound by exposure to media conditioned by AD-MSCs from healthy, elderly, and diabetic patients. Media conditioned by AD-MSCs from healthy patients promoted the migration of SMCs and did so in a dose-dependent manner; heating the media to 56°C eliminated the media's potency. AD-MSCs from diabetic and elderly patients had a decreased ability to differentiate into SMCs under angiotensin II stimulation; however, only AD-MSCs from elderly donors were unable to promote SMC migration. Gender and body-mass index of the patients showed no effect on either critical function of AD-MSCs. In conclusion, AD-MSCs from elderly patients may not be suitable for autologous TEBVs due to inadequate promotion of SMC migration and differentiation.
authors.affiliation: 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Krawiec
authors.forename: Justin S
authors.initials: JS
authors.lastname: Weinbaum
authors.forename: Claudette M
authors.initials: CM
authors.lastname: St Croix
authors.forename: Julie A
authors.initials: JA
authors.lastname: Phillippi
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: J Peter
authors.initials: JP
authors.lastname: Rubin
authors.forename: David A
authors.initials: DA
authors.lastname: Vorp
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D013045:Species Specificity; D033581:Stem Cell Transplantation; D023822:Tissue Engineering / Q000379:methods*