title: Regulation of the Stem Cell-Host Immune System Interplay Using Hydrogel Coencapsulation System with an Anti-Inflammatory Drug.
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 CAS-PASE-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.
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moshaverinia
authors.affiliation: School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Xingtian
authors.initials: X
authors.lastname: Xu
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Ansari
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
authors.affiliation: College of Dentistry, Ohio State University, 305 W 12th Ave, Columbus, OH 43210, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Schricker
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Paine
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Moradian-Oldak
authors.affiliation: Biomaterials Innovation Research Center Harvard Medical School 65 Landsdowne St, Rm 252, Cambridge, MA 02139, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Center for Craniofacial Molecular Biology (CCMB), Ostrow School of Dentistry, University of Southern California, 2250 Alcazar St, Los Angeles, CA 90033, USA.
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.affiliation: School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA.
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi