The use of allogeneic hematopoietic stem cell transplantation (HSCT) to
cure multiple disorders is limited by deficiency and dysregulation of T-cells.
Here we report a biomaterial-based scaffold that mimics features of T-cell
lymphopoiesis in the bone marrow. The bone marrow cryogel (BMC) releases bone
morphogenetic protein-2 to recruit stromal cells, and presents the Notch ligand
Delta-like ligand-4 to facilitate T-cell lineage specification of mouse and
human hematopoietic progenitor cells. BMCs subcutaneously injected in mice at
the time of HSCT enhanced T-cell progenitor seeding of the thymus, T-cell
neogenesis and diversification of the T-cell receptor repertoire. Peripheral
T-cell reconstitution increased ~6-fold in mouse HSCT and ~2-fold
in human xenogeneic HSCT. Furthermore, BMCs promoted donor CD4
+
regulatory T-cell generation and improved survival after allogeneic HSCT.
Compared with adoptive transfer of T-cell progenitors, BMCs increased donor
chimerism, T-cell generation and antigen-specific T-cell responses to
vaccination. BMCs may provide an off-the-shelf approach for enhancing T-cell
regeneration and mitigating graft-versus-host disease in HSCT.