Stage of Program: Basic Research and Discovery Stage Programs
Engineering Embryonic Stem Cell Allografts for Operational Tolerance
Stem cells, like all transplants not derived from an identical twin, are subject to scrutiny by the immune system and, without medical interventions that suppress the immune system, are usually killed after transplantation. However, rare exceptions to this rule exist because a small fraction of transplant patients has been able to maintain their transplant in […]
Engineering Thymic Regeneration to Induce Tolerance
A healthy immune system produces T cells that can recognize and react against foreign molecules (antigens) to protect against infection, while leaving normal host cells with “self antigens” undamaged. All T cells are produced in the thymus from blood stem cells that migrate from the bone marrow. “Tolerant” T cells are those that have been […]
Donor natural killer (NK) cells as “veto” cells to promote donor-specific tolerance
A major issue in the use of stem cells or in organ transplantation in general is the need to overcome graft rejection. Unfortunately, the only means currently available involves the use of systemic immunosuppression which leaves the recipient at risk for opportunistic infections. This proposal will seek to use the donor’s immune cells to prevent […]
Application of Tolerogenic Dendritic Cells for Hematopoietic Stem Cell Transplantation
The immune system protects us from invading pathogens, but has to be kept in check to prevent harmful responses to our own tissues. Unique immune “suppressor” cells have been recently characterized that prevent harmful responses to our own cells and proteins. We have recently identified unique populations of white blood cells, called dendritic cells that […]
Generation of regulatory T cells by reprogramming
The goal of our research is to develop efficient methods for making a particular class of immune-system cells known as regulatory T cells (Tregs). Tregs have the potential to be useful in a wide variety of clinical situations. For instance, they could be used to control the harmful immune responses seen in patients with autoimmune […]
Maternal and Fetal Immune Responses to In Utero Hematopoietic Stem Cell Transplantation
The immune system is the body’s defense system against disease and can recognize foreign cells. Because of this, stem cells and organs that are transplanted from one person to another are usually “rejected” by the immune system, forcing doctors to use powerful immune suppressive drugs with severe side effects. This natural defense system will therefore […]
Thymus based tolerance to stem cell therapies
This proposal focuses on the role of the immune system in transplantation of derivatives of human pluripotent stem cells (hPSCs). A critical roadblock to successful cell replacement therapies, no matter what the disease or injury, is the fact that the immune system’s main function is to prevent the introduction of foreign substances into our bodies. […]
Purified allogeneic hematopoietic stem cells as a platform for tolerance induction
Blood and immune cells originate and mature in the bone marrow. Bone marrow cells are mixtures of blood cells at different stages of development, and include rare populations of blood-forming stem cells. These stem cells are the only cells capable of generating the blood system for the life of an individual. Bone marrow transplants (BMT) […]
Stem cell tolerance through the use of engineered antigen-specific regulatory T cells
Type 1 Diabetes (T1D) occurs as a consequence of uncontrolled immune activation, culminating in the destruction of insulin-producing beta-cells. Efforts to prevent or reverse diabetes have been limited by the lack of safe and effective immunotherapies coupled with the inability to restore insulin producing beta-cells. We believe proper immune control to self-tissues to be a […]
Stem cell differentiation to thymic epithelium for inducing tolerance to stem cells
The thymus is an organ that plays a key role in controlling immune responses and immune tolerance. The thymus promotes immune tolerance by deleting and removing self-reactive T cells from the immune system. In addition, the thymus also helps drive the production of important suppressor T cell populations like regulatory T cells that also control […]