Treatment of Reperfused Ischemia with Adipose-Derived Stem Cells in a Preclinical Swine Model of Myocardial Infarction

Abstract

The aim of the study was to determine the long-term effect of transplantation of adipose-derived stromal cells (ADSCs) in a preclinical model of ischemia/reperfusion (I/R). I/R was induced in 28 Goettingen minipigs by 120 min of coronary artery occlusion followed by reperfusion. Nine days later, surviving animals were allocated to receive transendocardial injection of a mean of 213.6 ± 41.78 million green fluorescent protein (GFP)-expressing ADSCs (n = 7) or culture medium as control (n = 9). Heart function, cell engraftment, and histological analysis were performed 3 months after transplantation. Transplantation of ADSCs induced a statistically significant long-lasting (3 months) improvement in cardiac function and geometry in comparison with control animals. Functional improvement was associated with an increase in angiogenesis and vasculogenesis and a positive effect on heart remodeling with a decrease in fibrosis and cardiac hypertrophy in animals treated with ADSCs. Despite the lack of cell engraftment after 3 months, ADSC transplantation induced changes in the ratio between MMP/TIMP. Our results indicate that transplantation of ADSCs, despite the lack of long-term significant cell engraftment, increases vessel density and prevents adverse remodeling in a clinically relevant model of myocardial infarction, strongly suggesting a paracrine-mediated effect. ADSCs thus constitute an attractive candidate for the treatment of myocardial infarction.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…Amelioration of IR damage has been described previously using MSCs, cardiac stem cells and induced pluripotent stem cells [307][308][309][310]. Transendocardial injections of ASCs in a minipig model of IR injury results in long-lasting improvements in cardiac function, along with increased angiogenesis and vasculogenesis [311]. Higher numbers of CD31+ve and vWF+ve cells have also been found in models of lung IR following ASC injection, suggesting increased vessel formation [312].…”

Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study

“…To date, ADSCs have become excellent candidates for research and clinical applications. Many studies have shown that ADSC transplantation efficiently improved almost all symptoms of certain diseases, such as liver fibrosis (Harn et al, 2012), nerve defects (Gu et al, 2012;Liu et al, 2011;Santiago et al, 2009), ischemia (Mazo et al, 2012;Rigol et al, 2010), skeletal muscle injury (Pecanha et al, 2012), passive chronic immune thrombocytopenia (Xiao et al, 2012), and myocardial infarction (Yang et al, 2012) in animals, and systemic sclerosis in humans (Riordan et al, 2009;Scuderi et al, 2013).…”

Adipose Stromal Cells Differentiate Along a Smooth Muscle Lineage Pathway Upon Endothelial Cell Contact via Induction of Activin A

“…[13][14][15][16][17][18][19] We and others have shown that isolated ASC phenotypically and functionally overlap substantially with pericytes and SMC. networks.…”