Genetic Approach To Prevent Allogenic Rejection Of hESC-Derived Cells
Genetic Approach To Prevent Allogenic Rejection Of hESC-Derived Cells
A method to prevent the allogeneic immune rejection of cells derived from human Embryonic Stem Cells (hESCs) without suppressing the entire immune system. They optimized humanized mice (Hu-mice) that were reconstituted with a functional human immune syste
San Diego, CA, United States
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Background

Most human embryonic stem cell (hESC)-derived allografts are rejected within five years of transplantation even under chronic immune suppression. The current strategy to address the allograft rejection is to use immunosuppressants that systemically suppress the entire immune response, often increasing the risk for cancer and infection. Therefore there is an unmet need for specific immune suppression that prevents transplant rejection as well as reduces side effects.


Technology Description

UCSD researchers have developed a method to prevent the allogeneic immune rejection of cells derived from human Embryonic Stem Cells (hESCs) without suppressing the entire immune system. They optimized humanized mice (Hu-mice) that were reconstituted with a functional human immune system that rejected hESCs and their derivatives. In addition, they established knock in hESCs that constitutively express CTLA4-Ig and PD-L1 before and after differentiation (CP hESCs). Allogenic CP hESC-derived teratomas, fibroblasts, and cardiomyocytes were found to be immune protected in Hu-mice, while cells derived from parental hESCs are effectively rejected.


Applications

This method could enable specific immune suppression and possibly prevent the allogeneic immune rejection of hESC-derived cells without the aid of immunosuppressants. As a result, the immunosuppressive risk of cancer and infection can be lowered. Therefore, this approach has therapeutic benefits when compared with standard immune suppression.


State Of Development

UCSD researchers have performed proof of concept experiments on a mouse model with a functional human immune system.


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