The field of regenerative medicine offers the exciting possibility that patients needing new cells, tissues, or organs will no longer depend on donors in the future. Issues like organ shortages and cell type incompatibility could become a thing of the past, replaced by safe, readily available solutions for anyone needing a transplant.
However, this revolutionary field still faces numerous challenges, including the complex task of instructing stem cells to transform into desired cell types for treatment. Even if the correct cells or tissues are produced and can function effectively in the body, the patient’s immune system may reject them. Current regenerative medicine treatments require systemic immunosuppression, exposing patients to potential threats such as viruses, bacteria, and cancer cells.
In a pioneering approach to addressing these challenges, researchers from the Medical University of South Carolina and the University of Florida collaborated on a unique strategy to treat type 1 diabetes (T1D). This involved a tagged beta cell transplant, combined with localized immune protection provided by specially tagged immune cells.
According to Dr. Leonardo Ferreira, a researcher at MUSC Hollings Cancer Center and a leading investigator of the study, this combination of stem cell engineering and regulatory T cell (Treg) engineering represents a significant step toward a readily available solution for treating T1D.
Their recent study, published in the journal Cell Reports, detailed a unique collaboration. This collaboration combined the beta cell engineering expertise from the University of Florida with the surgical and chimeric antigen receptor (CAR) T cell capabilities at Hollings.
For T1D patients, their immune system mistakenly attacks pancreatic beta cells, which produce insulin to regulate blood sugar levels. Without a reliable method to self-regulate blood glucose levels, patients must closely monitor their glucose and manage their insulin to maintain their health and avoid severe complications.
Currently, some patients with poorly managed T1D consider islet cell transplantation using beta cells from a donor. This procedure requires the patients to undergo lifelong immunosuppression to prevent the body from rejecting the foreign beta cells. Additionally, it depends on the availability of donor cells, which can involve long waits or may not be available at all.
To address this, the researchers developed an engineering strategy using tagged beta cells derived from stem cells. They also used Tregs, a type of immune cell that regulates the immune response, to provide localized immune protection.
In their experiment, the researchers transplanted beta cells, engineered from stem cells and tagged with a nonreactive marker, into immunodeficient mice. They found that these cells were integrated and began to produce functional insulin. However, when the mice were exposed to an aggressive type of immune cell, all the beta cells were killed, mirroring what happens in humans with T1D.
To prevent this response, the researchers introduced specialized Tregs tagged with CAR technology. This allowed the Tregs to recognize the marker on the transplanted beta cells. As a result, they observed that the transplanted beta cells remained safe and functional.
Dr. Ferreira was pleased with the results and looks forward to future research. He stated, “With this approach, we created both the lock and the key for establishing immune tolerance.”
Ferreira and his team are now planning to expand their research. They aim to develop a range of differentiated stem cells and tagged protective Tregs to target specific diseases, including certain cancers and autoimmune diseases.
Several questions remain, such as the specific marker to use for human transplantation and the duration of Treg-mediated immune protection. Future research is needed to answer these questions and confirm the effectiveness of this approach in humans. This could potentially transform type 1 diabetes from a complex, high-maintenance disease to one that can be managed much more easily.
