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High Efficiency Matrix Modulus-Induced Cardiac Differentiation of Human Mesenchymal Stem Cells inside a Thermosensitive Hydrogel.
MedLine Citation:
PMID:  22729021     Owner:  NLM     Status:  Publisher    
Mesenchymal stem cells (MSCs) experience an extremely low rate of cardiac differentiation after transplantation into infarcted hearts, in part due to the inability of stiff scar tissue in supporting differentiation. We hypothesized that delivering MSCs in a hydrogel with matched modulus as native heart tissue, should stimulate MSC differentiation into cardiac cells. We have developed a thermosensitive and injectable hydrogel suitable for the delivery of cells into the heart, and found that the appropriate gel modulus can differentiate MSCs into cardiac cells with high efficiency. The hydrogel was based on N-isopropylacrylamide, N-acryloxysuccinimide, acrylic acid, and poly(trimethylene carbonate)-hydroxyethyl methacrylate. The hydrogel solution can be readily injected through needles commonly used for heart injection, and is capable of gelling within 7s at 37(o)C. The formed gels were highly flexible with breaking strains (>300%) higher than that of native heart tissue, and moduli within the range of native heart tissue (1-140 kPa). Controlling the concentration of hydrogel solution resulted in hydrogels with three different moduli: 16, 45 and 65 kPa. The moduli were decoupled from the gel water content and oxygen diffusion, parameters that can also influence cell differentiation. MSCs survived in the hydrogels during the entire culture period, and it was observed that gel stiffness did not affect cell survival. After 14 days of culture, more than 76% of MSCs differentiated into cardiac cells in 45 and 65 kPa gels, as confirmed by the expression of cardiac markers at both the gene and protein levels. MSCs in the hydrogel with 65 kPa modulus had the highest differentiation efficiency. The differentiated cells also developed calcium channels for imparting electrophysiological property, and gap junctions for cell-cell communication. The differentiation efficiency reported in this study was much higher than differentiation approaches described in the literature such as chemical induction and co-culture of MSCs and cardiomyocytes. These results indicate that the novel hydrogel holds great promise for delivering MSCs into the infarcted heart for the regeneration of new heart tissue.
Zhenqing Li; Xiaolei Guo; Andre F Palmer; Hiranmoy Das; Jianjun Guan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-21
Journal Detail:
Title:  Acta biomaterialia     Volume:  -     ISSN:  1878-7568     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Department of Materials Science & Engineering, The Ohio State University, Columbus, OH, 43210.
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