Program Type: Discovery
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 […]
Induction of immune tolerance to human embryonic stem cell-derived allografts
Human embryonic stem cells (hESCs) can undergo unlimited reproduction and retain the capability to differentiate into all cell types in the body. Therefore, as a renewable source of various cell types, hESCs hold great promise for human cell replacement therapy. Significant progress has been made in establishing the conditions to differentiate hESCs into cells of […]
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 […]
Development of an immune tolerant hESC source for allogeneic cell therapy applications
Human embryonic stem cells (hESCs) are an ideal tissue source for cell replacement therapy (CRT). They have the potential for limitless self-renewal while retaining their ability to differentiate into a wide variety of cells and tissues. Since their first derivation in 1998, hESCs have been used in many studies in order to evaluate their potential […]
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) […]