Volume 25, Issue 15 p. 2296-2307
Full Paper

Regulation of the Stem Cell–Host Immune System Interplay Using Hydrogel Coencapsulation System with an Anti-Inflammatory Drug

Alireza Moshaverinia

Corresponding Author

Alireza Moshaverinia

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

E-mail: [email protected], [email protected]Search for more papers by this author
Chider Chen

Chider Chen

School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA, 19104 USA

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Xingtian Xu

Xingtian Xu

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Sahar Ansari

Sahar Ansari

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Homayoun H. Zadeh

Homayoun H. Zadeh

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Scott R. Schricker

Scott R. Schricker

College of Dentistry, Ohio State University, 305 W 12th Ave, Columbus, OH, 43210 USA

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Michael L. Paine

Michael L. Paine

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Janet Moradian-Oldak

Janet Moradian-Oldak

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Ali Khademhosseini

Ali Khademhosseini

Biomaterials Innovation Research Center, Harvard Medical School, 65 Landsdowne St, Rm 252, Cambridge, MA, 02139 USA

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Malcolm L. Snead

Malcolm L. Snead

Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA, 90033 USA

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Songtao Shi

Corresponding Author

Songtao Shi

School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA, 19104 USA

E-mail: [email protected], [email protected]Search for more papers by this author
First published: 05 March 2015
Citations: 64

Abstract

The host immune system is known to influence mesenchymal stem cell (MSC)-mediated bone tissue regeneration. However, the therapeutic capacity of hydrogel biomaterial to modulate the interplay between MSCs and T-lymphocytes is unknown. Here it is shown that encapsulating hydrogel affects this interplay when used to encapsulate MSCs for implantation by hindering the penetration of pro-inflammatory cells and/or cytokines, leading to improved viability of the encapsulated MSCs. This combats the effects of the host pro-inflammatory T-lymphocyte-induced nuclear factor kappaB pathway, which can reduce MSC viability through the CASPASE-3 and CASPASE-8 associated proapoptotic cascade, resulting in the apoptosis of MSCs. To corroborate rescue of engrafted MSCs from the insult of the host immune system, the incorporation of the anti-inflammatory drug indomethacin into the encapsulating alginate hydrogel further regulates the local microenvironment and prevents pro-inflammatory cytokine-induced apoptosis. These findings suggest that the encapsulating hydrogel can regulate the MSC-host immune cell interplay and direct the fate of the implanted MSCs, leading to enhanced tissue regeneration.

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