Long‐Term Evaluation of Myoblast Seeded Patches Implanted on Infarcted Rat Hearts

Abstract

Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient.

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization

“…The observed functional benefit corroborates previous studies including ours showing a reduced LV dilatation and stabilized cardiac function when biomaterials such as porous, solvent-casted or particle leached substrates of poly(glyocolic-co-caprolactone), poly(lactic-co-caprolactone) or polyurethane hydrogel matrices were implanted together with MSCs [9,10,[48][49][50] or skeletal myoblasts [4,51].The main advantages of the current patch design rely on its mechanical integrity and its very thin nature necessary for an adequate positioning on the beating heart that remained stable for at least 4 weeks. Furthermore, characteristics of our matrix, such as a versatile and cost-efficient production and functionalization technology, as well as high potential for custom-tailored and tissue-specific modification, guarantee straightforward scaling up of the biograft.…”

“…As previously reported [4], cardiac patch evaluation was carried out in an established surgical model of MI. 41 female Lewis rats (Janvier, Le Genest, France), weighing 230 g were anesthetized with isoflurane and oxygen (5% for induction and 2.5% for maintenance).…”

“…During the past decade, myocardial stem cell injection has provided encouraging clinical outcomes and might become an accepted therapy [2]. However, the ischemic myocardium represents a hostile environment and successful clinical implementation of cell therapy is thus hampered by several challenges, including poor survival of injected cells and their limited retention and engraftment [3][4][5].…”

“…Polymeric matrices aim at providing a favorable environment for ex vivo cell adhesion and growth, and for facilitated implantation onto the ischemic myocardium [4,[8][9][10][11][12][13].…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Only SM-NFs significantly prevented progression towards heart failure 9 months after treatment compared to the other groups, but this effect vanished 12 months after treatment. Interestingly, the systems were correctly incorporated into the cardiac tissue as newformed vessels were formed inside the DDS [97].…”