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. 2015 May;240(5):593-600.
doi: 10.1177/1535370214560957. Epub 2014 Nov 27.

Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

Yu Xia  1 , Kai Zhu  2 , Hao Lai  2 , Meidong Lang  3 , Yan Xiao  3 , Sheng Lian  3 , Changfa Guo  4 , Chunsheng Wang  4
Affiliations

Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

Yu Xia et al. Exp Biol Med (Maywood). 2015 May.

Abstract

Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.

Keywords: Copolymer; cardiac repair; hydrogel; mesenchymal stem cells; myocardial infarction.

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Figures

Figure 1
Figure 1
Characterizations of the isolated MSCs. (a) Flowcytometry results of the surface markers of MSCs. (b) Immunostaining of the surface markers of MSCs. (A color version of this figure is available in the online journal.)
Figure 2
Figure 2
Characterizations of the novel hydrogel. (a) The interior morphology of the PNIPAAm. (b) The interior morphology of the novel hydrogel. (c) Storage modulus from 20℃ to 40℃. (d) Viscosity from 20℃ to 40℃. (e) Water content from day 0 to day 14. (f) Water remaining from day 0 to day 14
Figure 3
Figure 3
The in situ thermosensitive gelation of the novel hydrogel. (A color version of this figure is available in the online journal.)
Figure 4
Figure 4
The retention and redistribution of grafted MSCs. (a) BLI signals in live animals at 2 h, 1 d, and 28 d. (b) DAPI-labeled grafted MSCs in myocardium of group 4. Scale bar = 50 µm. (c) BLI signals of retention at 2 h, 1 d, and 28 d. (d) BLI signals of redistribution at 2 h, 1 d, and 28 d. (* versus group 4, P < 0.01; # versus group 4, P > 0.05). (A color version of this figure is available in the online journal.)
Figure 5
Figure 5
The angiogenesis and interstitial fibrosis. (a) The PECAM-1-based angiogenesis (arrow) and Masson trichrome staining-based interstitial fibrosis. Scale bar = 50 µm. (b) Capillary density of four groups. (c) Collagen volume fraction of four groups. (* versus group 4, P < 0.01; ** versus group 4, P < 0.05). (A color version of this figure is available in the online journal.)
Figure 6
Figure 6
Heart function assessment. (a) Left ventricular fractional shortening. (b) Left ventricular ejection fraction. (* versus group 4, P < 0.01)
See this image and copyright information in PMC

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