Adult: Coronary: Basic ScienceAdipose-derived stem cell sheet under an elastic patch improves cardiac function in rats after myocardial infarction
Graphical abstract
Enhancement of functional preservation with adipose-derived stem cell (ADSC) therapy by poly(ester carbonate urethane) urea (PECUU) cardiac patch with extracellular matrix (ECM). Combining a biodegradable, elastic cardiac patch that incorporates a cardiac ECM-derived hydrogel with ADSC sheet therapy enhanced cardiac function over individual therapy, and was associated with greater engraftment of ADSCs and neovascularization with greater cell recruitment following subacute myocardial infarction.
Section snippets
Materials and Methods
All procedures were performed in accordance with the Revised Guide for the Care and Use of Laboratory Animals (National Institutes of Health, Bethesda, Md). Experimental protocols were approved by the Ethics Review Committee for Animal experimentation of the University of Pittsburgh (reference No. 17101554).
Generation of ADSCs Sheets from GFP Transgenic Rats and PECUU Cardiac Patch
ADSCs sheets were successfully generated from GFP gene transgenic F344 rats according to the protocol outlined in Figure 1, A. As assessed by hematoxylin and eosin and Masson's trichrome staining, the generated ADSCs sheets were layered with a few ADSCs and entirely stained with GFP antibody, whereas cardiac patches were formed by 3 layers of ADSC sheets, ECM, and PECUU sheet (Figure 1, B). Porcine heart ECM gel was entirely stained with hematoxylin in the region of the patch where PECUU fibers
Discussion
This study explored whether an ADSC sheet, implanted in concert with PECUU/ECM cardiac patch therapy, would enhance cell survival and therapeutic efficacy compared with single therapy of an ADSC sheet or patch alone. The results demonstrated that significantly more ADSCs could be engrafted on the surface of the LV, and LV contractility and remodeling were improved at the 8-week end point compared with single therapy with an ADSC sheet or patch. By histological assessment, LV wall thickness was
Conclusions
ADSC sheet and cardiac patch therapies represent promising approaches to preserve cardiac function following myocardial infarction. Combining a biodegradable, elastic cardiac patch that incorporates a cardiac ECM-derived hydrogel with ADSC sheet therapy enhanced cardiac function over individual therapy, and was associated with greater engraftment of ADSCs and neovascularization in the peri-infarct zone following subacute myocardial infarction. This multifaceted strategy may contribute to
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2023, European Journal of Pharmaceutical SciencesRegeneration Using Adipose-Derived Stem Cell Sheets in a Rabbit Meniscal Defect Model Improves Tensile Strength and Load Distribution Function of the Meniscus at 12 Weeks
2023, Arthroscopy - Journal of Arthroscopic and Related SurgeryCitation Excerpt :In recent years, cell sheets have been studied at various transplantation sites, and several reports indicated that MSC sheets and similar tissue-engineered constructs can be transplanted without a carrier to the transplantation site, where they could serve as a scaffold.32,33 ADSC sheets, which are expected to remain in place even without a scaffold and fixation, have been used for regeneration of the heart, esophagus, skin, and other organs.34-36 In orthopedics, ADSC sheets were utilized in nerve, cartilage, and ligament reconstructions.12,13,37
Towards clinical translation of the cell sheet engineering: Technological aspects
2023, Smart Materials in MedicineCitation Excerpt :For example, CSs placed on a denuded tooth root surface were surrounded with β-tricalcium phosphate [122]. Cell sheets delivered to the retina were reported to be spread and fixed by oil/gas tamponade when the eye chamber is filled with oil or gas to provide temporary pressure [49,55,121]. The process cycle of obtaining CSs and CS-based tissue-engineered constructs, from harvesting initial cell cultures to manufacturing and delivering the final therapy product, is very time-consuming.
Engineering stem cell therapeutics for cardiac repair
2022, Journal of Molecular and Cellular CardiologyCitation Excerpt :For example, the use of a PEGylated 3D fibrin patch for MSC delivery has been shown to increase cell viability and modulate cell function [141]. It is also reported that a bioengineered cardiac patch that combined a biodegradable, elastic poly(ester carbonate urethane) urea (PECUU) with a cardiac ECM-derived hydrogel and ADSC sheet enhances cardiac function over the treatment with a patch or ADSCs alone [142]. Using scaffolds of various elasticities for stem cell MI therapy may affect outcomes, by influencing cardiac differentiation, and hindering or supporting the mechanical dynamics of the heart [143–145].
This work was financially supported by Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and the Uehara Memorial Foundation Research Fellowship.