Abstract 231: Allogeneic Mesenchymal Stromal Cells Derived from the Chorionic Villi of Human Placentae Are a Superior Source of Progenitor Cells for Angiogenic Therapies

Abstract

Introduction: Autologous bone marrow mesenchymal stromal cells (ABMSCs) have been the focus for the treatment of myocardial and limb ischemia. The utility of ABMSCs is limited because, in addition to requiring an invasive procedure to harvest, the number and the regenerative capacity of ABMSCs decrease with age and comorbid conditions. A redirected focus on alternative sources of MSCs is warranted. Here we compare MSCs from adipose tissue (ASCs) and human placenta (pMSCs) for angiogenic therapies. Methods: ASCs and pMSCs were characterized using culture assays, flow cytometry and immunofluorescent staining. Immunodulatory properties were assessed using mixed lymphocyte reactions (MLR). Inflammatory and angiogenic cytokines were quantified using ELISA. The ability of ASCs and pMSCs to restore perfusion in a murine model of hindlimb ischemia was compared. Results: ASCs and pMSCs expressed cell surface antigens consistent with MSCs. In permissive cultures, ASCs and pMSCs stained positive for Oil Red O (adipogenic), Alcian Blue (chondrogenic) and alkaline phosphatase (osteogenic) in addition to neural and myogenic lineages. Immunofluorescent staining demonstrated that PMSCs but not ASCs express embryonic stem cell antigens Oct-3/4, Nanog, SSEA-3 and SSEA-4. ASCs and pMSCs demonstrated immunosuppressive properties in MLRs (n=3). There was a significant reduction of MNC proliferation when cultured with pMSCs (96.5 ± 3.7 % reduction; p < 0.001) or ASCs (93.27 ± 2.3 % reduction; p < 0.001). When compared to ASCs, pMSCs (n=3) secrete significantly greater quantities of VEGF (4.4 ± 0.13 vs. 2.5 ± 0.031 ng/mL; p < 0.001), HGF (2.4 ± 0.114 vs. 1.6 ± 0.173 ng/mL; p < 0.001), and Ang-1 (4.6 ± .23 vs. 1.6 ± 0.016 ng/mL; p < 0.001) in hypoxia. In NOD/SCID mice with femoral artery ligation (n=6), those treated with pMSCs demonstrated a significant improvement in perfusion compared to those treated with ASCs at 35 days post-treatment (56.18 vs. 40.82; p < 0.001). Conclusion: In conclusion, while both ASCs and pMSCs have potent immunosuppressive properties, pMSCs are superior in the production of angiogenic cytokines and restoration of perfusion in ischemic tissue. PMSCs can be banked and thus made readily available for the treatment of acute ischemic syndromes.