Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium

BACKGROUND Pluripotent stem cell-derived cardiomyocytes(CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac tissue.AIM We investigated the regenerative potential of mouse embryonic stem cell(ESC)-derived platelet-derived growth factor receptor-α(PDGFRα)+ cardiac lineagecommitted cells(CLCs), which have a proliferative capacity but are in a morphologically and functionally immature state compared with differentiated CMs.METHODSWe induced mouse ESCs into PDGFRα+ CLCs and αMHC+ CMs using a combination of the small molecule cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197.We implanted PDGFRα+ CLCs and differentiated αMHC+ CMs into a myocardial infarction(MI) murine model and performed functional analysis using transthoracic echocardiography(TTE) and histologic analysis.RESULTS Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs based on TTE.In histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFRα+ CLCs aligned and integrated with host CMs and were mostly differentiated into α-actinin+ CMs,and they did not convert into CD31+ endothelial cells or αSMA+ mural cells.CONCLUSION PDGFRα+ CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFRα+ CLCs may represent a potential cellular resource for cardiac regeneration.

Healing of the nasal septal mucosa in an experimental rabbit model of mucosal injury

Objective:The aim of this study was to investigate the regeneration process of the nasal mucosa after a surgically created mucosal defect in the rabbit nasal septum,and to evaluate the effects of different interventions.Methods:A 7 mm-diameter circular mucosal defect was made in the septum of forty New Zealand white rabbits.The rabbits were divided into four groups (ten rabbits in each group) according to the type of intervention;no treatment (control),silastic sheet (SS),hyaluronic acid (HA),and silastic sheet and hyaluronic acid (SS + HA) group.The diameter of the defect,mucosal thickness,epithelial thickness,and ciliated cell count were evaluated every week for five weeks.Results:The average diameter of the defect in the control group were 5.1,3.65,1.2,0.75,and 0.05 mm at postoperative 1,2,3,4,and 5 weeks.In the SS group,the diameter decreased to 4.35,2.1,0.35,0.15,and 0 mm at postoperative 1,2,3,4,and 5 weeks,respectively,in which the mean diameter of the postoperative week 2 was significantly smaller compared to control (3.65 mm vs.2.1 mm,P =0.039).For the HA group and SS + HA group,the diameter of the defect did not show a significant difference from the control group during the five weeks.The mucosal thickness,epithelial thickness,and ciliated cell count of the regenerated mucosa were not significantly different among the groups.Conclusion:The regeneration process of the nasal septal mucosa was identified using a novel rabbit model.Mucosal regeneration can be accelerated by applying silastic sheets.