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.

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair

“…Live imaging and tumor measurements showed that injection of encapsulated hMSCs expressing hemopexin-like proteins adjacent to glioblastoma tumors in nude mice led to a significant reduction in tumor volume (87%) and weight (83%). Alginate hydrogels (elastic modulus ¼ 22 kPa; average pore diameter ¼ 600 nm) have also been shown to augment BM-MSC-mediated bone regeneration by inhibiting the penetration of two pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-a) and interferon gamma (IFN-g) [229]. Consequently, cell apoptosis was significantly decreased.…”

Integrin‐Mediated Interactions Control Macrophage Polarization in 3D Hydrogels

“…For example, novel biomaterial surfaces [7] , improved immune-instructive biomaterials [8] and incorporated immune modulating cells (e.g. stem cells) [9] could influence the wound healing process. Within the same context, there are several studies in which the phenotype of macrophages inside different 3D biomaterial environment has been studied [10] .…”

Dental and orofacial mesenchymal stem cells in craniofacial regeneration: The prosthodontist’s point of view

“…Alginate microspheres can fill the gaps of irregularly shaped defects, enabling minimally invasive surgical procedures. Moshaverinia et al 65–67 used alginate hydrogel for the first time as a scaffold for PDLSCs and GMSCs. In their studies, they developed an injectable alginate hydrogel delivery system for PDLSCs and GMSCs.…”