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Related Experiment Videos

Tolerance induction post in utero stem cell transplantation.

M J Cowan1, S H Chou, A F Tarantal

  • 1Pediatric Bone Marrow Transplant Division, University of California, San Francisco 94143-1278, USA.

Ernst Schering Research Foundation Workshop
|December 6, 2000
PubMed
Summary

In utero hematopoietic stem cell (HSC) transplantation offers potential for early curative therapy but faces challenges with low engraftment and limited tolerance induction in non-defective fetuses. Further research is needed to overcome graft-versus-host disease while promoting engraftment.

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Area of Science:

  • Immunology
  • Hematology
  • Transplantation Medicine

Background:

  • In utero hematopoietic stem cell (HSC) transplantation presents an alternative to postnatal bone marrow transplantation (BMT), potentially avoiding intensive conditioning.
  • Early gestation HSC engraftment is possible in MHC-mismatched fetal recipients, but pluripotent HSC engraftment rates are generally low, except in severe combined immunodeficiency (SCID).

Purpose of the Study:

  • To investigate the efficacy of in utero HSC transplantation for diseases like thalassemia and assess engraftment and tolerance induction in non-defective fetal models.
  • To explore the role of donor cell type and location in achieving tolerance post-transplantation.

Main Methods:

  • Studies were conducted in non-defective fetal mouse and rhesus monkey models to evaluate HSC engraftment, rejection, and tolerance induction.

Related Experiment Videos

  • Experiments involved assessing microchimerism, skin graft tolerance, and the impact of co-injecting dendritic cell (DC) precursors and donor c-kit+ cells.

    • Main Results:

    • While microchimerism was observed in approximately 75% of mouse recipients, permanent skin graft tolerance was achieved in less than 10%.
    • Co-injection of DC precursors did not enhance tolerance, and recruitment of donor c-kit+ cells did not appear sufficient for tolerance induction.
    • Fetal monkey models showed similar patterns of low donor cell engraftment and limited tolerance induction. Graft-versus-host disease (GVHD) was observed in mice receiving both allogeneic marrow and DC.

    Conclusions:

    • In utero HSC transplantation in non-defective fetuses results in low engraftment and limited tolerance, suggesting challenges for treating conditions like thalassemia.
    • The type and location of engrafted donor cells are critical for tolerance induction.
    • Future research should focus on strategies to block graft-versus-host reactions while preserving the graft-promoting functions of donor T cells.