We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation.
- Authors
Shah, Nisarg J.; Mao, Angelo S.; Shih, Ting-Yu; Kerr, Matthew D.; Sharda, Azeem; Raimondo, Theresa M.; Weaver, James C.; Vrbanac, Vladimir D.; Deruaz, Maud; Tager, Andrew M.; Mooney, David J.; Scadden, David T.
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for multiple disorders, but deficiency and dysregulation of T cells limit its utility. 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. In comparison to 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. A bone marrow-like scaffold improves T cell regeneration after hematopoietic stem cell transplantation.
- Publication
Nature Biotechnology, 2019, Vol 37, Issue 3, p293
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/s41587-019-0017-2