Vitner Einat B, Bovone Giovanni, Jung Wei-Hung, Lou Junzhe, Hankenson Hugh, Dacus Mason T, Binenbaum Yoav, Adu-Berchie Kwasi, Stafford Alexander G, Sobral Miguel C, Mooney David J
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
The Wyss Institute for Biologically Inspired Engineering Harvard University, Boston, MA, 02138, USA.
Adv Healthc Mater. 2025 Jun 17:e2501529. doi: 10.1002/adhm.202501529.
Regulatory T cells (T) maintain immune homeostasis and their adoptive transfer is being widely explored to mitigate inflammatory and autoimmune conditions. Here a biomaterial is developed to accumulate T at a specific anatomic location to bypass the need for ex vivo T isolation and adoptive transfer. It is first shown that eliglustat, an FDA-approved inhibitor of UDP-glucose ceramide glucosyltransferase, promotes T from both naïve and activated CD4 T cells in vitro. Click-crosslinked cryogels fabricated from alginate and collagen allow for a sustained release of CXCL10 or CXCL11, and when injected in subcutaneous tissues led to the enrichment of effector and memory T cells to the scaffolds. Loading eliglustat into these cryogels significantly enhances the local accumulation of T in vivo. These findings demonstrate that eliglustat-loaded cryogels offer a simple yet effective biomaterial strategy to boost T directly in vivo, potentially providing a targeted method to treat various inflammatory and autoimmune diseases.
调节性T细胞（Treg）维持免疫稳态，其过继转移正在被广泛探索以减轻炎症和自身免疫性疾病。在此，开发了一种生物材料，用于在特定解剖位置积累Treg，从而无需体外分离和过继转移Treg。首先表明，依利格鲁司他是一种经美国食品药品监督管理局（FDA）批准的UDP-葡萄糖神经酰胺葡萄糖基转移酶抑制剂，在体外可促进初始和活化CD4 T细胞产生Treg。由藻酸盐和胶原蛋白制成的点击交联冷冻凝胶可实现CXCL10或CXCL11的持续释放，当注射到皮下组织时，可使效应和记忆Treg细胞富集到支架上。将依利格鲁司他加载到这些冷冻凝胶中可显著增强体内Treg的局部积累。这些发现表明，负载依利格鲁司他的冷冻凝胶提供了一种简单而有效的生物材料策略，可直接在体内增强Treg，有可能提供一种靶向治疗各种炎症和自身免疫性疾病的方法。
