Background 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). Methodology/Principal Finding Si-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/Significance These 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.

Purpose: We hypothesized that the injection of mesenchymal stem cells (MSC) within an hydrogel would improve efficacy of cell therapy after myocardial infarction (MI). We have developed an hydrogel composed to Hydroxypropyl methylcellulose Silanyzed (Si-HPMC). Methods: The cytocompatibility was evaluated by the MSC viability cultivated in 3D within the hydrogel using cytotoxicity assays. Immediately after coronary ligation, hydrogel, 3.106 MSCs alone or with the hydrogel (MSC+hydrogel) were injected into the myocardium of rats (PBS used as control). Cardiac function was assessed using echocardiography over 56 days and left ventricular (LV) remodeling was assessed using histopathology. Results: The hydrogel maintained the MSC viability during the whole culture period. In the PBS group, MI induced a reduction in left ventricular ejection fraction (LVEF) (87.4±1.5% at baseline vs 47.4±2.4% at 56 days; p<0.001) and an increase in LV diameters during the whole study. The injection of MSC+hydrogel in acute phase of MI induced an significant increased of LVEF at day 7 up to day 56 as compared to PBS group (at day 56: 47.4±2.4% in PBS group vs 68.5±2.0% in MSC+hydrogel group; p<0.001) and an increase as compared to day 1 after MI (61.2±2.9% at day 1 vs 76.4±1.5 % at day 28; p<0.001 as compared to day 1). The injection of hydrogel alone induced an increase in LVEF at 28 days as compared to PBS group but not at day 7 and 56 and the injection of MSC induced an increase at 28 and 56 days as compared to PBS group, but not at day 7. In the both groups the LV diameters and LVEF are not significantly altered during the whole study as compared to day 1. Interestingly when animals have been treated with MSC+hydrogel, their LVEF was higher at day 7 as compared to EF in MSC group and at day 56 in compared to hydrogel group. Conclusion: These results showed the major effects of Si-HPMC hydrogel are observed at the short-term. In acute phase of MI, the MSC delivery with hydrogel allowed a better preservation of cardiac function and LV remodeling as compared to injection of MSC alone.

Interest has increased in the use of exogenous stem cells to optimize lung repair and serve as carriers of a therapeutic gene for genetic airway diseases such as cystic fibrosis. We investigated the survival and engraftment of exogenous stem cells after intratracheal injection, in a murine model of acute epithelial airway injury already used in gene therapy experiments on cystic fibrosis. Embryonic stem cells and mesenchymal stem cells were intratracheally injected 24 hr after 2% polidocanol administration, when epithelial airway injury was maximal. Stem cells were transfected with reporter genes immediately before administration. Reporter gene expression was analyzed in trachea-lungs and bronchoalveolar lavage, using nonfluorescence, quantitative, and sensitive methods. Enzyme-linked immunosorbent assay quantitative results showed that 0.4 to 5.5% of stem cells survived in the injured airway. Importantly, no stem cells survived in healthy airway or in the epithelial lining fluid. Using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining, transduced mesenchymal stem cells were detected in injured trachea and bronchi lumen. When the epithelium was spontaneously regenerated, the in vivo amount of engrafted mesenchymal stem cells from cell lines decreased dramatically. No stem cells from primary culture were located within the lungs at 7 days. This study demonstrated the feasibility of intratracheal cell delivery for airway diseases with acute epithelial injury.