The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function

Abstract

Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1-thus rationalizing the integration of fibronectin and fibrinogen into a supportive intracapsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.

Cardiac Stem Cell Treatment in Myocardial Infarction

“…For CSC transplantation therapy, several biomaterials and enhancing proteins show great promise in boosting the effects of CSC therapy, enhancing effects that we cannot quantify in our analyses because of their heterogeneity and small sample size. Nonetheless, it is possible that biomaterials, 45 growth factors (eg, insulinlike growth factor/hepatic growth factor), 46,47 and other compounds or proteins like necrostatin 48 and pim-1 49 can boost retention, survival, biological function, and ultimately the regenerative effects of cell therapy. Furthermore, we excluded all studies that did not report an EF measurement; hence, studies reporting only our secondary outcomes were not included in our analysis.…”

Purinergic Signaling in Early Inflammatory Events of the Foreign Body Response: Modulating Extracellular ATP as an Enabling Technology for Engineered Implants and Tissues

“…Mayfield et al delivered cardiac stem cells encapsulated in agarose to help repair an induced myocardial infarction in mice. 111 While delivery of encapsulated stem cells did improve cardiac function and reduce infarct size, and survival of encapsulated cells was significantly greater than nonencapsulated cells, the number of transplanted encapsulated cells remaining was only 20% at 1 h and 10% at 3 weeks postdelivery. In combination with the data on the innate immune response to scaffold-based materials, it can be inferred that just as the neutrophil response generates collateral damage to host tissues, neutrophils may also destroy a large number of implanted cells.…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…On the other hand, MPs can be formulated to encapsulate [107,108] or to convey [37,109] cells on their surface. Nevertheless, although alginate and matrigel MPs have reported promising results [107,108], only few studies have been performed with MPs made of synthetic materials.…”

“…Nevertheless, although alginate and matrigel MPs have reported promising results [107,108], only few studies have been performed with MPs made of synthetic materials. In a recent study human amniotic fluid SCs (1x10 6 ) were encapsulated inside PLGA porous MPs of about 250 µm.…”