2 research outputs found
Hemopressin-Based pH-Sensitive Hydrogel: A Potential Bioactive Platform for Drug Delivery
Peptides
with proper sequences are capable of self-assembling into
well-defined nanostructures, which can subsequently grow and entangle
into three-dimensional nanomatrices. In this study, hemopressin, a
cannabinoid receptor-modulating peptide derived from the α-chain
of hemoglobin known to self-assemble into nanofibrils, was examined
for its potential applicability as a gelator. The results indicated
that hemopressin’s gel formation was dependent on pH and salt
concentration. Although hemopressin’s macroscopic states showed
differences, its microscopic structure remained largely unchanged
in which it consisted mainly of the antiparallel β-sheet conformation
as confirmed by FTIR (C=O stretch peaks at 1630 and 1695 cm<sup>–1</sup>) and CD (β-sheet peak at 195 nm). The major difference between
the gel and sol states was displayed in the fibril length in which
the gelation at pH 7.4 resulted in 4 ÎĽm fibrils, whereas the
solution at pH 5.0 showed 800 nm fibrils. The pH-dependent sol–gel
phase transition property was then utilized for the investigation
of the pH-responsive release of FITC-dextran (4–40 kDa) from
hemopressin fibrillary gel. Finally, the biocompatibility of the peptide
was demonstrated by proliferation assay of cultured bone marrow mesenchymal
stem cells. Altogether, the results suggested that hemopressin is
a potentially promising candidate as a therapeutically active platform
for drug delivery
Cell Therapy with Embryonic Stem Cell-Derived Cardiomyocytes Encapsulated in Injectable Nanomatrix Gel Enhances Cell Engraftment and Promotes Cardiac Repair
A significant barrier to the therapeutic use of stem cells is poor cell retention <i>in vivo</i>. Here, we evaluate the therapeutic potential and long-term engraftment of cardiomyocytes (CMs) derived from mouse embryonic stem cells (mESCs) encapsulated in an injectable nanomatrix gel consisting of peptide amphiphiles incorporating cell adhesive ligand Arg-Gly-Asp-Ser (PA-RGDS) in experimental myocardial infarction (MI). We cultured rat neonatal CMs in PA-RGDS for 7 days and found that more than 90% of the CMs survived. Next, we intramyocardially injected mouse CM cell line HL-1 CMs with or without PA-RGDS into uninjured hearts. Histologic examination and flow cytometry analysis of digested heart tissues showed approximately 3-fold higher engraftment in the mice that received CMs with PA-RGDS compared to those without PA-RGDS. We further investigated the therapeutic effects and long-term engraftment of mESC-CMs with PA-RGDS on MI in comparison with PBS control, CM-only, and PA-RGDS only. Echocardiography demonstrated that the CM-only and CM+PA-RGDS groups showed higher cardiac function at week 2 compared to other groups. However, from 3 weeks, higher cardiac function was maintained only in the CM+PA-RGDS group; this was sustained for 12 weeks. Confocal microscopic examination of the cardiac tissues harvested at 14 weeks demonstrated sustained engraftment and integration of mESC-CMs into host myocardium in the CM+PA-RGDS group only. This study for the first time demonstrated that PA-RGDS encapsulation can enhance survival of mESC-derived CMs and improve cardiac function post-MI. This nanomatrix gel-mediated stem cell therapy can be a promising option for treating MI