An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation

Nat Biotechnol. 2019 Mar;37(3):293-302. doi: 10.1038/s41587-019-0017-2. Epub 2019 Feb 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Bone Marrow
  • Bone Marrow Transplantation*
  • Chimerism
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Mice
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Tissue Scaffolds*
  • Transplantation, Heterologous / methods
  • Transplantation, Homologous