Table 4.

Pre-Clinical trials conducted on stem cell therapies (Tompkins et al., 2018).

Types of stem cell	Small animal trials	Large animal trials
Bone marrow-derived mesenchymal cells	Small animal trials have presented an auspicious upshot after acute myocardial infarction. Reduction of the infarct size and also fibrosis. Onward of left ventricular ejection fraction and vasculogenesis. Excessive amenities includes-reduced apoptosis reduced fibrosis and improved vascular endothelial growth factor expression. Enhance the regional blood flow in the infarct zone.	In the swine, acute and chronic myocardial infarction model, not only the autologous but also allogeneic mesenchymal cells showed a better result. Improvement in left ventricular ejection fraction and reduction of scar size and also improvement thickness. In the no-infarcted region, contractility was increased.
Adipose-derived stem cells	Adipose-derived stem cells and bone marrow-derived mesenchymal cells are administered intramyocardially into the rats after one week of post-myocardial infarction. None of them improve angiogenesis or reduced the infarct size. But the adipocyte-derived cells increase left ventricular ejection fraction. CD29+ and CD29+ cell markers of the adipose tissues decreased the infarct size and promote the left ventricular function.	These cells were used in the rabbits which had chronic ischemia. After 3 weeks of myocardial infarction, the rabbits have administrated adipose-derived cells into the infracted myocardium. Results include- Eminent vascular density left ventricular ejection fraction, end-diastolic volume compared with the 5-week post-injection. Allogenic adipose-derived cells improved perfusion but they did not improve the left ventricular ejection fraction in the porcine model when given via intracoronary. After the administration of adipose-derived cells in humanized pigs, 4 weeks post-myocardial infarction, there was improved perfusion and decreased infarct size in higher concentrations. Lower concentration did not show any effects.
CSCs/Cardiac progenitor cells	Cardiac c-kit cells are capable of self-renewal and they operate in a multipotent and clonogenic system to yield cardiomyocytes, smooth muscle cells and endothelial cells. They show more engraftment and individualization. better improvement in remodelling and reduced scar size compared to mesenchymal. They acted thirty-fold better than MSCs.	In a chronic ischemic swine model, intracoronary administration of c-kit+ CSCs into pigs 3 months post-MI demonstrated the therapeutic efficacy of these cells. Beginning 1-month post-injection, the LVEF rose in the cell-treated group and there was a regional increase in cardiac function. CSCs engrafted and some differentiated into cardiomyocytes and vascular structures.
Cardio spheres and cardio sphere-derived cells	Allogenic cardio derived cells were injected into rats by the intracoronary route and resulted in a decreased scar size and improved cardiac function, myocyte cycling and angiogenesis. Allogenic cardiac cells are proved efficient in the revitalization of senescent rats.	Treatment with cardio derived cells showed a beneficial treatment in acute and chronic myocardial infarction. These effects are mediated by cardio derived exosomes.
Bone marrow-derived mononuclear cells	Bone marrow-derived mononuclear cells were administrated intramyocardially and the results represented that this cell therapy promotes vasculogenesis at two weeks post-injection. But in the four-week group, there did not show any increase in vascularity. It may have been secondary to the maturation of the scar.	Improvement of wall thickening occurred four weeks after myocardial infarction. There also noticed a rise in the vascularization of the myocardium and a decline in the scar size. Bone marrow-derived mononuclear cells showed a variable result in the ventricular function in large animal models.
Pluripotent Stem Cells	Administration of the pluripotent stem cells in the myocardium of the mice via direct injection results in increased heart function and engraftment. Wall thickness was increased and declined fibrosis. But the long-term benefit of using pluripotent stem cells is not properly studied.	In the large animal study, the combination of pluripotent stem cells and human mesenchymal cells were used in swine. The combination of the cells increased vasculogenesis. But these therapies increase capillary density and sometimes caused apoptosis.