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Trans-inner Cell Mass Injection of Embryonic Stem Cells Leads to Higher Chimerism Rates
Published on: May 29, 2018
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Megadose stem cell administration as a route to mixed chimerism
1Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Current Opinion in Organ Transplantation
|June 7, 2014
Summary
Mismatched haploidentical stem cell transplants show promise for inducing immune tolerance before organ transplantation. Novel
Area of Science:
- Immunology
- Transplantation Medicine
- Regenerative Medicine
Background:
- Mismatched haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is explored for inducing immune tolerance.
- Traditional T-cell depleted haplo-HSCT with megadose CD34+ progenitors aims to reduce graft-versus-host disease and rejection.
- Mixed chimerism is crucial for allograft tolerance but achieving it with T-cell replete haplo-HSCT poses risks.
Purpose of the Study:
- To review innovations in mismatched haploidentical HSCT for immune tolerance induction.
- To highlight the role of 'veto' cells in facilitating mixed chimerism.
- To discuss the application of nonmyeloablative conditioning in haplo-HSCT protocols.
Main Methods:
- Review of recent advancements in haplo-HSCT strategies.
- Focus on the use of novel 'veto' cells for immune modulation.
- Analysis of nonmyeloablative conditioning regimens.
Main Results:
- Megadose CD34+ progenitor transplants exhibit 'veto' capacity to overcome rejection.
- Studies indicate mixed chimerism is essential for human allograft tolerance.
- Nonalloreactive 'veto' cells, like anti-third-party CD8 T cells, may prevent graft-versus-host disease.
Conclusions:
- Stable mixed chimerism is achievable via haplo-HSCT, paving the way for organ tolerance.
- Coadministration of 'veto' cells with haplo-HSCT under nonmyeloablative conditioning shows promise.
- This approach may enable transplantation as a prelude to organ acceptance.
