Moshaverinia, AlirezaChen, ChiderXu, XingtianAnsari, SaharZadeh, Homayoun H.Schricker, Scott R.Paine, Michael L.Moradian-Oldak, JanetKhademhosseini, AliSnead, Malcolm L.Shi, Songtao2023-05-222023-05-222015-04-152021-05-03https://repository.upenn.edu/handle/20.500.14332/8828The 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.This is the pre-peer reviewed version of the following article: [Moshaverinia, A., Chen, C., Xu, X., Ansari, S., Zadeh, H. H., Schricker, S. R., . . . Shi, S. (2015). Regulation of the stem Cell–Host immune system interplay using hydrogel coencapsulation system with an Anti‐Inflammatory drug. Advanced Functional Materials, 25(15), 2296-2307. doi:10.1002/adfm.201500055]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.DentistryArticle