Reduction of infarct size by intravenous injection of uncultured adipose derived stromal cells in a rat model is dependent on the time point of application

Abstract

Stem cell therapy is a promising tool to improve outcome after acute myocardial infarction (AMI), but needs to be optimized since results from clinical applications remain ambiguous. A potent source of stem cells is the stromal vascular fraction of adipose tissue (SVF), which contains high numbers of adipose derived stem cells (ASC). We hypothesized that: 1) intravenous injection can be used to apply stem cells to the heart. 2) Uncultured SVF cells are easier and safer when cultured ASCs. 3) Transplantation after the acute inflammation period of AMI is favorable over early injection. For this, AMI was induced in rats by 40min of coronary occlusion. One or seven days after AMI, rats were intravenously injected with vehicle, 5×10(6) uncultured rat SVF cells or 1×10(6) rat ASCs. Rats were analyzed 35 days after AMI. Intravenous delivery of both fresh SVF cells and cultured ASCs 7 days after AMI significantly reduced infarct size compared to vehicle. Similar numbers of stem cells were found in the heart, after treatment with fresh SVF cells and cultured ASCs. Importantly, no adverse effects were found after injection of SVF cells. Using cultured ASCs, however, 3 animals had shortness of breath, and one animal died during injection. In contrast to application at 7 days post AMI, injection of SVF cells 1 day post AMI resulted in a small but non-significant infarct reduction (p=0.35). Taken together, intravenous injection of uncultured SVF cells subsequent to the acute inflammation period, is a promising stem cell therapy for AMI.

Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model

“…Consistent with previous findings [28,29], H&E and Picrosirius red/fast green staining revealed that the hearts of recipients of ADSCs had a smaller scar area compared with those that Fig. 4.…”

Rapid Induction of Osteogenic Markers in Mesenchymal Stem Cells by Adipose-Derived Stromal Vascular Fraction Cells

“…SVF cells, which are traditionally isolated through enzymatic processing, contain MSCs, endothelial (progenitor) cells, immune cells, smooth muscle cells, pericytes and other stromal components [18]. SVF treatment has been shown to provide therapeutic effects similar to those of ASC treatment in osteochondral defects and myocardial infarction [19, 20], and SVF cells have been demonstrated to have similar neuroprotective effects and greater immunomodulatory properties than ASCs in experimental chronic autoimmune encephalitis studies [21]. The regenerative capacity of SVF cells has been validated in various therapeutic models, such as fat grafting, multiple sclerosis, burn injury, diabetes, radiation, Crohn’s disease, cardiac disease and bone defect models [13, 14].…”

A Proliferation and surface marker characterization of adipose stem cells after culture in various processed outdated platelet lysate containing media

“…Cell size is an important factor especially when cells are injected intravenously, since larger cells can lead to obstruction of the lung. 34 It has been indicated that cells with a smaller cell size have a higher differentiation capacity. 35 The inability of hADSC to become confluent when cultured in FBS containing DMEM high glucose medium might be due to higher ROS production and thus could promote cell death.…”