Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for hematological malignancies and immunologic disorders, but allogeneic HSCT is limited by deficiency and dysregulation of T-cells. We aimed to enhance post-HSCT T-cell reconstitution and hypothesized that a T-cell lymphopoietic bone marrow niche might be engineered to foster production of T-cell progenitors in vivo, which can undergo host-driven selection. To test this hypothesis, we created an injectable biomaterial-based scaffold that promotes T-cell development in vivo by recapitulating key features of the bone marrow niche. The composite device, referred to as a bone marrow cryogel (BMC), is comprised of a macroporous hydrogel-based scaffold permitting cellular infiltration. The presentation of T-lineage cues in a bone marrow-like microenvironment enhanced thymic seeding of progenitors and facilitated the enhancement of donor T-cell reconstitution after HSCT in mice. The BMC-reconstituted T-cells were functional, with a diverse T-cell receptor repertoire and modulated GVHD. BMC may represent a simple to administer, off-the-shelf approach to post-HSCT T-cell regeneration.
Citation Format: Nisarg Shah, David J. Mooney. Enhanced T-cell immunity in vivo using injectable bioengineered scaffolds [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B043.