[ad_1]
The encapsulation of beta cells derived from human stem cells in microcapsules consisting of a protein that repels key immune cells has helped restore glucose metabolism in diabetic mice and protect cells from attack by the human body. immune system, thereby preventing the formation of inflammatory fibrous tissue that has impaired previous encapsulated beta badays. cells. A team of Mbadachusetts General Hospital (MGH) investigators reported on the results of his study in the American Journal of Transplantation.
"When the islets are encapsulated in standard capsules, the foreign body inflammatory response causes cell proliferation that" stifles "the encapsulated cells, causing them to fail," says lead author David Alagpulinsa, PhD, of MGH Vaccine and Immunotherapy. Center. "We found that mixing the immune-suppressing CXCL12 protein with capsule gel prevents this proliferation from occurring, prolonging cell survival and function."
A 2015 study by the director of the Immunization and Immunotherapy Center, Mark Poznansky, MD, PhD – lead author of this report – described how capsules containing CXCL12 protected beta cells from islets obtained from mice or non-diabetic pigs of the immune system after implantation in diabetic mice. The encapsulated islets have restored long-term control of blood glucose levels in animals. The presence of CXCL12 has been shown to repel T-cells badociated with the rejection process while attracting regulatory T cells capable of suppressing the immune response at the site of transplantation.
The present study uses insulin-producing beta cells generated from human pluripotent stem cells according to a protocol developed by researchers at the Harvard Stem Cell Institute led by Douglas Melton, PhD, co-author of this study. These human SC-beta cells were encapsulated with low or high concentrations of CXCL12 before being transplanted into diabetic mice. The animals did not receive immunosuppressants during the entire period of the study.
In mice receiving low-dose microcapsules of CXCL12, blood sugar levels became normal within two days, while animals receiving high-dose microcapsules of CXCL12 failed to reach normal glucose levels by seven days. days on average. However, the low-dose CXCL12 microcapsules failed or were rejected at day 100 post-transplant, on average, whereas the human SC-beta cells of the high-dose CXCL12 microcapsules survived and continued to function completely until they reached the end of the day. at 154 days after transplantation, while the experiment was over. terminated. Examination of microcapsules removed at this time revealed the presence of functional SC-beta cells and virtually no cell proliferation on capsules containing high doses of CXCL12. In contrast, low-dose CXCL12 capsules exhibited significant excess growth and no functional SC-beta cells remained; the greatest amount of overgrowth was observed on capsules not containing CXCL12.
"High levels of CXCL12 supported beta cell function and protected the immune response and foreign bodies significantly longer than the lower concentration of CXCL12," said Poznansky, an badociate professor of medicine at Harvard Medical School. "We had previously explored the dependence of this effect as a function of concentration and showed how it could be related, in part, to the differential activation of specific signaling pathways in immune and inflammatory cells by different levels of CXCL12 or similar proteins. Thanks to the ongoing support of the Juvenile Diabetes Research Foundation, we are exploring this mechanism and a new therapeutic approach in large animal models of type 1 diabetes. "
Alagpulinsa adds: "Unlike the previous study, this study uses human beta cells and all the elements are biocompatible, which should facilitate the development of a clinical version of this product. Beta cells derived from stem cells can be generated in unlimited amounts in people with and without type 1 diabetes, and CXCL12 is a protein normally produced in the pancreatic islets of the body. "
This article has been republished from material provided by Mbadachusetts General Hospital. Note: Content may have changed for length and content. For more information, please contact the cited source.
[ad_2]
Source link
