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In utero allogeneic hematopoietic stem cell transplantation to induce tolerance
K Hajdu1, S Tanigawara, L K McLean
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, USA.
Fetal Diagnosis and Therapy
|July 1, 1996
Summary
In utero hematopoietic stem cell transplantation can induce tolerance in mice. Donor cells were detected in 5.6% of recipients, establishing tolerance to donor-specific skin grafts.
Area of Science:
- Immunology
- Transplantation Biology
- Developmental Biology
Background:
- In utero hematopoietic stem cell transplantation (IUHCT) is a potential strategy for inducing immune tolerance.
- Establishing tolerance prenatally could prevent graft rejection and the need for lifelong immunosuppression.
Purpose of the Study:
- To evaluate the efficacy of IUHCT in inducing tolerance in a fetal mouse allogeneic model.
- To determine the rate of engraftment and the development of specific immune tolerance post-transplantation.
Main Methods:
- Fetal liver cells were transplanted into normal mouse allogeneic recipients.
- Engraftment was assessed by detecting donor cells postnatally.
- Tolerance was evaluated using skin grafting from the prenatal donor and a third-party strain.
- Chimerism was reestablished using anti-H-2 monoclonal antibody conditioning for re-transplantation.
Main Results:
- Donor cells were detected in 5.6% of surviving recipients (9/162).
- Higher cell doses (> 10^6 cells/fetal gram) improved engraftment rates.
- Mice with chimerism showed tolerance to donor-specific skin grafts but rejected third-party grafts.
- Monoclonal antibody conditioning facilitated reestablishment of chimerism and tolerance.
Conclusions:
- IUHCT can induce specific immune tolerance in a mouse model.
- Engraftment rates and tolerance are dose-dependent.
- Chimerism is crucial for establishing prenatal tolerance.
- Conditioning strategies can enhance IUHCT efficacy for tolerance induction.