Folic Acid Derived Hydrogel Enhances the Survival and Promotes Therapeutic Efficacy of iPS Cells for Acute Myocardial Infarction

Abstract

Stem cell therapy has obtained extensive consensus to be an effective method for post myocardial infarction (MI) intervention. Induced pluripotent stem (iPS) cells, which are able to differentiate into multiple cell types, have the potential to generate cardiovascular lineage cells for myocardial repair after ischemic damage, but their poor retention rate significantly hinders the therapeutic efficacy. In the present study, we developed a supramolecular hydrogel which is formed by the self-assembly of folic acid (FA)-modified peptide via a biocompatible method (glutathione reduction) and suitable for cell encapsulation and transplantation. The iPS cells labeled with CM-Dil were transplanted into the MI hearts of mice with or without FA hydrogel encapsulation. The results corroborated that the FA hydrogel significantly improved the retention and survival of iPS cells in MI hearts post injection, leading to augmentation of the therapeutic efficacy of iPS cells including better cardiac function and much less adverse heart remodeling, by subsequent differentiation toward cardiac cells and stimulation of neovascularization. This study reported a novel supramolecular hydrogel based on FA-peptides capable of improving the therapeutic capacity of iPS cells, which held big potential in the treatment of MI.

Supermolecules as Medicinal Drugs

“…iPS cells labeled with CM-Dil were transplanted into MI mice hearts with or without FA hydrogel encapsulation. The results confirmed that FA hydrogel significantly improved the retention and survival of iPS cells in MI hearts after injection, resulting in enhanced therapeutic efficacy of iPS cells, including better cardiac function and less adverse cardiac remodeling, followed by cardiomyocytes [46].…”

Tissue Engineering Therapies Based on Folic Acid and Other Vitamin B Derivatives. Functional Mechanisms and Current Applications in Regenerative Medicine

“…Recently, Li et al used folic acid as an adjuvant in a cell therapy based on induced pluripotent stem cells (iPSCs) for cardiac regeneration after an acute myocardial infarction [42]. After modifying folic acid with a specific peptide sequence (FA-FFFRGD-ss-EE, FA-Seq), they used it as a pro-gelator to synthesize the injectable hydrogel.…”

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy

“…[123] Yang and colleagues modified their peptide hydrogelator with folic acid (FA) to generate FA-functionalized hydrogel, which significantly improved the retention and survival of pluripotent stem (iPS) cells. [124] Li and colleagues reported a new peptide gelator (Nap-FFRGD) to encapsulate vascular endothelial growth factor (VEGF), and the resulting hydrogel enhanced blood capillary density in mice. [125] In addition to a direct chemical modification to the chemical structures, [126] co-assembly strategy was also explored to functionalize SPHs.…”