Epicardial placement of human MSC-loaded fibrin sealant films for heart failure: Preclinical efficacy and mechanistic data

Abstract

Mesenchymal stromal cell (MSC) transplantation has been investigated as an advanced treatment of heart failure; however, further improvement of the therapeutic efficacy and mechanistic understanding are needed. Our previous study has reported that epicardial placement of fibrin sealant films incorporating rat amniotic membrane-derived (AM)-MSCs (MSC-dressings) could address limitations of traditional transplantation methods. To progress this finding toward clinical translation, this current study aimed to examine the efficacy of MSC-dressings using human AM-MSCs (hAM-MSCs) and the underpinning mechanism for myocardial repair. Echocardiography demonstrated that cardiac function and structure were improved in a rat ischemic cardiomyopathy model after hAM-MSC-dressing therapy. hAM-MSCs survived well in the rat heart, enhanced myocardial expression of reparative genes, and attenuated adverse remodeling. Copy number analysis by qPCR revealed that upregulated reparative genes originated from endogenous rat cells rather than hAM-MSCs. These results suggest hAM-MSC-dressing therapy stimulates a secondary release of paracrine factors from endogenous cells improving myocardial repair ("secondary paracrine effect"), and cardiac M2-like macrophages were identified as a potential cell source of repair. We demonstrated hAM-MSCs increased M2-like macrophages through not only enhancing M2 polarization but also augmenting their proliferation and migration capabilities via PGE 2 , CCL2, and TGF-b1, resulting in enhanced cardiac function after injury.

Recent Advances in Cardiac Patches: Materials, Preparations, and Properties

“…23,24 Ghazizadeh et al 25 induced differentiation of ESCs, trans- 26,27 Rou et al 28 treated MSCs with cell growth factor and transforming growth factor and showed accelerated gene expression and production of spindle-shaped myotubes, suggesting that MSCs can be converted to cardiomyocytes by growth factors and can promote myocardial repair. Studies have also been performed using fibronectin 29 and chitosan 30 to make cardiac patches with MSCs, and both showed that the patches promoted myocardial repair. Numerous studies have demonstrated the ability of MSCs as seed cells for myocardial repair, but the differentiation of MSCs to cardiomyocytes in vivo is less efficient.…”

Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease

“…After administration of hAM-MSCs dressing to mice with ischemic cardiomyopathy, it was found that the dressing could improve myocardial remodeling by promoting the secondary release of paracrine factors from endogenous cells and promoting the polarization of the M1 phenotype to the M2 phenotype of macrophages. So, hAM-MSCs dressing can slow down the development of heart failure ( Fields et al, 2021 ). Pura-Matrix hydrogel with MSCs applied to mouse epicardium after MI, found that it could inhibit the development of inflammation, promote the formation of myocardial capillary, reduce interstitial fibrosis, improve cardiac function and alleviate the progression of heart failure by secreting cytokines such as IL-10 ( Ichihara et al, 2018 ).…”

The NSUN5-FTH1/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells

“…Mesenchymal stem cell (MSC) transplantation is an important treatment option for acute liver failure as well as for cardiac and neurodegenerative diseases [ 1 – 3 ]. Bone marrow-derived mesenchymal stem cells (BMSCs) can home to injured tissues and contribute to tissue repair [ 4 ].…”