Abstract

BackgroundTo improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI).Methodology/Principal FindingSi-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI.Conclusion/SignificanceThese beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

Highlights

  • After myocardial infarction (MI), left ventricular (LV) remodeling occurs with early and progressive extracellular matrix (ECM) degradation, infarct zone expansion, scar thinning, LV enlargement and eventually, transition to heart failure [1,2]

  • We used a rat model to evaluate the effects of injecting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with mesenchymal stem cell (MSC) on cardiac function and LV remodeling in a rat model of MI

  • When considering stem cell-based cardiac tissue engineering, the ideal hydrogel should be biocompatible with respect to MSC and cardiac tissue and should be injectable into the myocardium to provide the advantage of minimally invasive delivery [26]

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Summary

Introduction

After myocardial infarction (MI), left ventricular (LV) remodeling occurs with early and progressive extracellular matrix (ECM) degradation, infarct zone expansion, scar thinning, LV enlargement and eventually, transition to heart failure [1,2]. We previously designed a water-rich hydrogel consisting of silanized hydroxypropyl methylcellulose (Si-HPMC) that can be steam sterilized [21] and supports the diffusion of signaling molecules and nutrients [22]. This Si-HPMC hydrogel can be injected together with MSC in vivo and is able to self-crosslink to form a scaffolding matrix [23]. To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI)

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