Stanford physician-scientist Alice Bertaina, MD, PhD, associate professor of pediatrics, has received about $18 million from the California Institute for Regenerative Medicine (CIRM) for a clinical trial to allow kidney transplantation without the need for long-term immunosuppression.
Dr. Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that combines blood stem cell (HSC) transplantation with kidney transplantation to improve outcomes for children. This approach aims to improve blood stem cell preparation through an immune-based purification process.
In this approach, donor HSCs are transplanted into the patient to prepare for acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney, providing the opportunity to avoid the long-term need for medications that suppress the immune system.
Preclinical data support the idea that this approach could allow the patient to stop taking immunosuppression medications, which carry significant long-term risks.
Scientific finding found that attenuation of CD3 zeta ITAMs of TCR signaling has an apparently negligible impact on maturation of innate-line T cells which took long dwell time to grow and high signal intensity were markedly impacted. This is follow by activation of some intermediates such as Erk and Akt was strongly attenuated, whereas calcium mobilization and activation of NF-KB,Jnk and P38 were unimpaired. This condition may favor the Treg cells development. Experimental study showed that attenuation of CD3 zeta ITAMs in mice increased Treg production in both thymus and peripherally derived T cells of animal model. Treg cells provide a powerful tool to suppress immune system from rejecting organ donor. Therefore, harvesting of HSC and attenuation of CD3 zeta ITAMs may enhance development of Treg cells which can be competitive as an immunsuppressing drug to prevent organ donor from rejection.