ArticleScience translational medicine2023
Selective Bcl-2 inhibition promotes hematopoietic chimerism and allograft tolerance without myelosuppression in nonhuman primates.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Preclinical and clinical studies on kidney allograft tolerance via hematopoietic chimerism.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Review
- Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes.JCI insight · 2026Article
- Synergistic venetoclax and anti-CD3 therapy for control of alloreactive response in hematopoietic stem cell transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Development of a 24-h Preservation Protocol of Forearm Vascularized Composite Allotransplants in Nonhuman Primates Using Subnormothermic Machine Perfusion.Transplantation direct · 2025Article
- Allogeneic Liver Transplantation in Nonhuman Primates: Surgical Technique With Stable Postoperative Outcomes.Transplantation direct · 2025Article
- Chimerism and immunological tolerance in solid organ transplantation.Seminars in immunopathology · 2025Review
- Cardiac allograft tolerance can be achieved in nonhuman primates by donor bone marrow and kidney cotransplantation.Science translational medicine · 2025Article
- CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients.Science translational medicine · 2025Article
- Effect of transport stress on apoptosis and autophagy in goat lung cells.Frontiers in veterinary science · 2025Article
- Organ-Specific Determinants of Tolerance and the Unique Challenge of Vascularized Composite Allotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- [Advances and perspectives in vascularized composite allotransplantation preservation].Bulletin de l'Academie nationale de medecine · 2024Article
- Enhanced VCA Storage: A Pilot Study Demonstrating Supercooling in Orthotopic Rodent Hindlimb Transplantation.Transplantation proceedings · 2024Article
- Accelerating drug discovery and repurposing by combining transcriptional signature connectivity with docking.Science advances · 2024Article
- De novo membranous nephropathy in a pig-to-baboon kidney xenograft: A new xenograft glomerulopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
Hematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression and other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic stem cell (HSC) engraftment, it appears essential to establish niches for the donor HSCs by depleting the host HSCs. To date, this has been achievable only by nonselective treatments such as irradiation or chemotherapeutic drugs. An approach that is capable of more selectively depleting host HSCs is needed to widen the clinical application of HSCT. Here, we show in a clinically relevant nonhuman primate model that selective inhibition of B cell lymphoma 2 (Bcl-2) promoted hematopoietic chimerism and renal allograft tolerance after partial deletion of HSCs and effective peripheral lymphocyte deletion while preserving myeloid cells and regulatory T cells. Although Bcl-2 inhibition alone was insufficient to induce hematopoietic chimerism, the addition of a Bcl-2 inhibitor resulted in promotion of hematopoietic chimerism and renal allograft tolerance despite using only half of the dose of total body irradiation previously required. Selective inhibition of Bcl-2 is therefore a promising approach to induce hematopoietic chimerism without myelosuppression and has the potential to render HSCT more feasible for a variety of clinical indications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.