Table 1.
Cardiovascular preclinical trials using stem cell-derived secretome.
| Disease/delivery | Animal model | Source of CM | Outcome | Reference |
|---|---|---|---|---|
| Limb ischaemia— Daily injection of 40 μl of human adipose-derived stem cell (ADSC) CM for 7 days into the gracilis muscle | Athymic mice | Human adipose-derived stem cells | Enhanced endothelial cell growth, CD34+ cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion. | Bhang et al. (2014) |
| Limb ischaemia— Single injection of human embryonic stem cell-derived endothelial-like cell (ESC-EC) CM and/or circulating proangiogenic cells (PACs) into the gracilis muscle | SCID mice | Human embryonic stem cell-derived endothelial-like cells | Neither diabetic PACs nor CM from ESC-ECs improve blood flow recovery and angiogenesis. In contrast, both transplantations of proangiogenic cells from controls or diabetic patients supplemented with ESC-ECs CM improve blood flow and angiogenesis. | Ho et al. (2012) |
| Limb ischaemia— Three weekly intramuscular injections of endothelial progenitor cells (EPCs), EPC-CM, or control medium | Athymic nude rats | Human peripheral blood endothelial progenitor cells | Both EPC-CM and EPCs increase limb blood flow assessed and neovascularization. EPC-CM transplantation stimulates the mobilization and recruitment of bone marrow-derived EPCs. | Di Santo et al. (2009) |
| Limb ischaemia— Two intramuscular weekly injections of human amniotic liquid derived stem cells (AFSC) CM (topically applied to thigh muscles) for a total treatment-duration of two weeks | SCID mice | Human amniotic liquid derived cKit stem cells | Increased arteriogenesis, capillary density, total perfusion area, and mobility. | Mirabella et al. (2012) |
| Myocardial infarction— Peri-infarct injection of human adipose-derived stem cells (ADSC), ADSC-CM or control medium immediately after MI | SCID and C57BL/6 mice | Human adipose-derived stem cells | Improved cardiac function, reduced infarct size, increased reparative angiogenesis, reduced cardiomyocyte apoptosis The effect of ADSCs on the first 3 outcomes was superior to that of ADSC-CM. | Yang et al. (2013) |
| Myocardial infarction— Intramyocardial injections of either concentrated CM derived from STRO-3- mesenchymal precursor cells cultured in serum-free medium or control medium at 48 h after MI | Athymic nude rats | Human STRO-3- mesenchymal precursor cells | Improved ventricular function, reduced ventricular dilatation, and infarct size, increased neovascularization. | See et al. (2011) |
| Myocardial infarction— Intravenous treatment with CM from human embryonic stem cells-derived MSCs or control medium initiated 4 h after coronary artery ligation with the treatment continued for 7 days twice daily via a catheter inserted into the jugular vein | Pigs | Human embryonic stem cells-derived MSCs | Increased capillary density, reduced infarct size improved myocardial performance. | Timmers et al. (2011) |
| Myocardial infarction— At the end of 2 h reperfusion, three cycles of intracoronary infusion CM from porcine endothelial progenitor cells or vehicle | Pigs | Porcine peripheral blood endothelial progenitor cells | Increased angiogenesis, improved cardiomyocyte remodeling and contractility. | Hynes et al. (2013) |