Stephan Ramos

All Publications

• Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes. JCI insight Ramos, S. A., Bhagchandani, P., Burgos, D. M., Gu, X., Rodriguez, R., Nourin, N., Neukam, M., Pathak, S., Shizuru, J., Kim, S. K. 2026

  Abstract

  Mixed hematopoietic chimerism after hematopoietic cell transplantation (HCT) can modulate the immune system and induce tolerance to allogeneic tissues. However, bone marrow conditioning-related toxicities preclude wider adoption of HCT for transplant allotolerance. We sought agents that reduced conditioning intensity, while promoting durable mixed chimerism after HCT across complete major histocompatibility complex (MHC) mismatch in diabetic mice, permitting islet allotransplantation and diabetes reversal. We systematically tested baricitinib (JAK1/2 inhibitor), venetoclax (Bcl2 inhibitor), and alphaCD47 antibody, agents in current clinical use, and quantified hematopoietic chimerism after HCT. Combined with alphaCD117 antibody, transient T cell depletion, and just 10 centigray (cGy) total body irradiation (TBI), these agents enabled durable mixed chimerism and matching allo-islet tolerance, to cure diabetes without evidence of GVHD. Thus, we have developed a conditioning regimen to promote allogeneic mixed hematopoietic chimerism and transplanted islet allotolerance that minimizes conditioning radiation and cures diabetes, a significant achievement.

  View details for DOI 10.1172/jci.insight.194491

  View details for PubMedID 42013280

• Curing autoimmune diabetes in mice with islet and hematopoietic cell transplantation after CD117 antibody-based conditioning. The Journal of clinical investigation Bhagchandani, P., Ramos, S. A., Rodriguez, B., Gu, X., Pathak, S., Zhou, Y., Moon, Y., Nourin, N., Chang, C. A., Poyser, J., Velasco, B. J., Zhao, W., Kwon, H., Rodriguez, R., Burgos, D. M., Miranda, M. A., Meyer, E., Shizuru, J. A., Kim, S. K. 2025

  Abstract

  Mixed hematopoietic chimerism after allogeneic hematopoietic cell transplantation (HCT) promotes tolerance of transplanted donor-matched solid organs, corrects autoimmunity, and could transform therapeutic strategies for autoimmune type 1 diabetes (T1D). However, development of non-toxic bone marrow conditioning protocols is needed to expand clinical use. We developed a chemotherapy-free, non-myeloablative (NMA) conditioning regimen that achieves mixed chimerism and allograft tolerance across MHC barriers in NOD mice. We obtained durable mixed hematopoietic chimerism in prediabetic NOD mice using anti-c-Kit monoclonal antibody, T-cell depleting antibodies, JAK1/2 inhibition, and low-dose total body irradiation prior to transplantation of MHC-mismatched B6 hematopoietic cells, preventing diabetes in 100% of chimeric NOD:B6 mice. In overtly diabetic NOD mice, NMA conditioning followed by combined B6 HCT and islet transplantation durably corrected diabetes in 100% of chimeric mice without chronic immunosuppression or graft-versus-host disease (GVHD). Chimeric mice remained immunocompetent, as assessed by blood count recovery and rejection of 3rd party allogeneic islets. Adoptive transfer studies and analysis of autoreactive T cells confirmed correction of autoimmunity. Analysis of chimeric NOD mice revealed central thymic deletion and peripheral tolerance mechanisms. Thus, with NMA conditioning and cell transplantation, we achieved durable hematopoietic chimerism without GVHD, promoted islet allograft tolerance, and reversed established T1D.

  View details for DOI 10.1172/JCI190034

  View details for PubMedID 41252212