Allogeneic Cardiospheres Safely Boost Cardiac Function and Attenuate Adverse Remodeling After Myocardial Infarction in Immunologically Mismatched Rat Strains

Abstract

Allogeneic cardiospheres increase viable myocardium, decrease scar, improve function, and attenuate adverse remodeling in the infarcted rat heart, without deleterious immunological sequelae. These observations lay the groundwork for developing cardiospheres as a novel off-the-shelf microtissue product for myocardial regeneration.

Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction

“…Cardiosphere-derived cells (CDCs) (26) are a unique heartderived cell type that confers functional and structural benefits, including reduction of infarct size, improvement of cardiac function, enhanced angiogenesis, and modulation of the inflammatory response after MI (27)(28)(29)(30)(31). Recently, in a porcine model, we have found that CDCs are able to confer acute cardioprotection when administered 30 minutes after IR (a phenomenon called "cellular postconditioning"; ref.…”

Cadaveric cardiosphere-derived cells can maintain regenerative capacity and improve the heart function of cardiomyopathy

“…9 Furthermore, allogeneic CDC transplantation without immunosuppression induces only a transient mild local immune reaction in a rat myocardial infarction (MI) model. [10][11] The CADUCEUS (CArdiosphere-Derived aUtologous Stem CElls to Reverse ventricUlar dySfunction) trial proved the efficacy and safety of CDC transplantation for treatment of MI. 12 Recently, Mohammad et al found that CDC treatment prevents functional deterioration, attenuates oxidative stress, promotes cardiomyocyte proliferation, and reduces mortality in a transgenic mouse model of dilated cardiomyopathy (DCM).…”

Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction

“…Finally, our phenotyping ended 2 months after cell treatment in this study. Although our previous work indicates that the benefits of CDCs can last even longer,10, 14 more‐extended evaluation would be valuable, particularly in terms of hard clinical endpoints, such as progression to heart failure.…”

“…A total of 3 to 5 sections obtained from the border zones were evaluated per heart with immunostaining for Isolectin (Invitrogen I21411; Invitrogen, Carlsbad, CA) and α‐smooth muscle actin (α‐SMA; ab5694; Abcam). Masson's trichrome staining (Sigma‐Aldrich, St. Louis, MO) was performed on serial sections for tissue collagen quantification 10. To measure apoptotic cardiomyocytes, sections from myocardial samples underwent immunostaining for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL; Roche 12156792910; Roche, Indianapolis, IN) and α‐sarcomeric actinin (ab9465; Abcam).…”