L. P. Brewster1,2, J. Raykin1,2 1Emory University School Of Medicine,Surgery,Atlanta, GA, USA 2Atlanta VA Medical Center,Surgery And Research Services,Decatur, GA, USA
Introduction: Diabetic persons undergo premature aging of their vasculature leading to an earlier onset and more severe presentations of cardiovascular disease. Thus, they have great need for regenerative therapies. Mesenchymal stem cells (MSC) are one promising regenerative therapy that may help prevent vascular complications of diabetes. The objective of this work is to identify whether MSC survival pathways are improved by platelet lysate (PL), and if so, whether PL gel confers benefit to MSC survival and regenerative function on endothelial cells (EC).
Methods:
MSCs from Diabetic PAD (dMSC) and healthy patients were used. Luminescence studies were performed in MSCs transfected with luciferin lentivirus. Secretome analysis was performed with RayBiotech angiogenesis assays. Akt cell survival pathways were quantified by multiplex analyses.
Results: dMSCs and healthy MSCs have increased retention and survival (2-3x) in PL gel than that seen in saline injection (most commonly used clinically). EGF expression in dMSCs is significantly increased (>5x; P<.0001) in PL gel over that in control groups. dMSCs had significant down-regulation of pAKT compared to healthy MSCs and MSCs from PAD patients without diabetes. Further, PL drastically changes the secretome profile of dMSCs compared to FBS. (Figure
Conclusion:
Initial concerns with cells from cardiovascular patients have now come into question for PAD patients. Improving dMSC survival could be important to PAD patients. In this work, we show that PL gel improves MSC survival in vivo and dMSC EGF expression, and that dMSCs have Akt signaling defects that may be reversible with PL supplementation.
