Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart

Abstract

Human multipotent adipose-derived stem cells (hMADSCs) have recently been isolated featuring extensive expansion capacity ex vivo. We tested the hypothesis that hMADSC transplantation might contribute to cardiac functional recovery by its direct or indirect effect on myocardial infarction (MI). Nude rats were either transplanted with hMADSCs or PBS (control) in ischemic myocardium immediately following MI. Echocardiographical assessment of cardiac function after MI with hMADSCs showed significant improvement of each parameter compared to that with PBS. Histological analysis also showed significantly reduced infarct size and increased capillary density in peri-infarct myocardium by hMADSC treatment. However, remarkable transdifferentiation of hMADSCs into cardiac or vascular lineage cells was not observed. Despite the less transdifferentiation capacity, hMADSCs produced robust multiple pro-angiogenic growth factors and chemokines, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor-1a (SDF-1a). Specifically, hMADSC-derived SDF-1a had a crucial role for cooperative angiogenesis, with the paracrine effect of hMADSCs and Tie2-positive bone marrow (BM) progenitor recruitment in ischemic myocardium. hMADSCs exhibit a therapeutic effect on cardiac preservation following MI, with the production of VEGF, bFGF, and SDF-1a showing paracrine effects and endogenous BM stem/progenitor recruitment to ischemic myocardium rather than its direct contribution to tissue regeneration.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…Finally, recent studies suggest that AKT/c-myc signaling pathways may mediate increased VEGF secretion in ASCs as the injection of constitutively active AKT/v-myc-expressing ASCs promote better wound healing compared to normal controls [330]. However, the role of other secreted factors cannot be ruled out as suppression of HGF production by ASCs through RNA interference significantly impairs ischemic tissue revascularization [321] and SDF-1 from ASCs has been identified as being involved in myocardial vascularization [331]. From these studies, it can be concluded that the ASC is capable of increasing vascularization in regenerating tissues-most likely through a combined action of direct endothelial differentiation and paracrine action.…”

CD34+ cell therapy is safe and effective in slowing the decline of hepatic reserve function in patients with decompensated liver cirrhosis

“…[6][7][8][9] Furthermore, several groups have recently completed clinical trials of autologous BM cell therapy in patients with liver disease.…”

The Combination of Vascular Endothelial Growth Factor and Stromal Cell-Derived Factor Induces Superior Angiogenic Sprouting by Outgrowth Endothelial Cells

“…This combination of factors may potentially increase microvessel density in tissue-engineered vascular networks as well as in models of cancer or ischemic disease [31,32]. The results of these experiments also emphasize the enhanced sprouting capacity of OECs compared to that of mature endothelial cells, and support further investigation of the clinical uses of these cells.…”