Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

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.

Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology

“…A number of other groups also demonstrated that MSCs possess the ability to differentiate into cardiomyocytes. Indeed, studies have demonstrated that engrafted MSCs in vivo can improve cardiac function and remodeling 11–13 .…”

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

“…New Zealand white rabbits aged 5-6 months, weighing 2.6 ± 0.4 kg (Shanghai Sixth People's Hospital, SCXK: 2012-0007), were recruited, and a model of MI was established using the modified Fujita method as previously described [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. The rabbits were first anesthetized by ear vein injection of 3% pelltobarbitalum natricum (30 mg/kg), and fixed using a surgical stent on supine position without tracheal intubation and mechanical ventilation (the tongue was pulled out to keep airway patency).…”

“…As known, MI could promote an irreversible and massive loss of cardiomyocytes, followed by gradual replacement with fibrous noncontractile cells, and could finally lead to heart failure [5,6]. Traditionally, treatments of MI always tend to slow down the progression to heart failure by pharmacological agents and interventional therapies [7,8].…”

Second-harmonic generation microscopy for assessment of mesenchymal stem cell-seeded acellular dermal matrix in wound-healing

“…In the co-cultured ADM scaffolds, MSC proliferation was quantitatively assessed by measuring the fluorescence intensity of GFP using ImageJ (NIH) software in 3D mode [22]. After seeding onto the ADM scaffolds, most of the MSCs attached to the plates and ADM scaffolds after 6 h of incubation.…”