First transplants of immunotolerant allogeneic cells revealed



For the first time, researchers have found a way to prevent the immune rejection of allogeneic cell and tissue transplants derived from iPSC protein.

Although Induced Pluripotent Stem Cells (iPSCs) provide a source of cells that spread unrestrictedly and can be differentiated into any tissue in the body, they can not be used in acute organ repair strategies. because of the generation, differentiation and proliferation of) iPSCs are time consuming and laborious.

Transplants of cells or tissue prefabricated from iPSC donors, however, gave a vigorous immune response against histoinfective cells. In Nature Biotechnology, an international team of researchers led by Sonja Schrepfer (USCF, San Francisco) and Hermann Reichenspurner (Hamburg-Eppendorf University Hospital) presents for the first time a way around the problem by equipping allogeneic CSPs with the "Allergic CSP". an "invisible immunity cloak". "That makes them invisible to the immune system." This is an important step on the way to developing universal stem cell therapy, "said Schrepfer." Donor organs are declining in the world and waiting lists for organ transplants are lengthening, "added Reichenspurner." We are in dire need of alternative therapeutic strategies for patients with 39; organ. A promising strategy is cell therapy, which replaces organs or tissues with new cells derived from stem cells. "According to first author, Tobias Deuse," it's the first time manufactured cells that can be transplanted universally and can survive in immunocompetent recipients without eliciting an immune response. "

The researchers overexpressed the CD47 molecule, which inhibits the immune tolerance of cells and fetal organs in pregnant women by sending a "do not eat me" signal against innate immune system cells such as macrophages and NK cells. in both cases. human and allogeneic human IPSC mice, and more particularly the inactivation of class I and II major histocompatibility complex (MHC) genes, which exhibit antigens foreign to the immune system. The resulting iPSCs were not attacked by the immune system of humanized mice. In addition, iPSCs have retained their potential for pluripotent stem cells and their ability to differentiate.

Endothelial cells, smooth muscle cells and cardiomyocytes derived from these mouse or human hypoimmunogenic iPSCs have reliably escaped immune rejection in allogeneic recipients completely free of MHC and have survived in the long term without immunosuppression. According to Schrepfer, "the production of iPS cells derived from the patient is time consuming and expensive, quality controls are difficult and cell generation varies considerably from patient to patient". Researchers now have an alternative: to produce universal iPS cells, design them to prevent immune rejection and differentiate cell or tissue grafts for immediate use. "Our technique can benefit more people with lower production costs than any individualized approach," said Deuse. "We only need to make our cells once and we still have a product that can be applied universally."


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