Growing Exogenous Human Organs in Pigs: Meeting a Growing Unmet Need
Abstract
Diabetes is a new age epidemic. In the United States, 34.2 million Americans of all ages (10.5 % of the population; 2018 statistics) are diagnosed with diabetes, with nearly 1.6 million Americans including 187,000 children diagnosed with Type I diabetes (Source: National Diabetes Statistics Report, 2020; https://www.cdc.gov/diabetes/pdfs/data/statistics/nationaldiabetes-statistics-report.pdf). The prevalence of diabetes is more than double among Veterans (25%), who are at a higher risk due to bodily injuries and service-related exposure. It is estimated that total economic burden of diabetes is about 327 billion dollars per year. The medical costs for diabetic patients are estimated to be ~2.3 times that of non-diabetic patients. Taken together, diabetes is an economic as well as a health burden to United States and worldwide. Nearly 1.5 million Americans are diagnosed with diabetes every year, with the numbers expected to spike every year. Currently, there is no cure for Type I diabetes other than injectable insulin. Among alternative therapeutic options, cellular therapy specifically introducing primary insulin producing beta cells or islet cells (cluster of hormone producing cells including beta cells in pancreas) is strongly considered as a means for consistent and long-term relief from injectables that suffer from drawback such as pain at the site of injections, infections, and diabetic coma or death due to wrong dosage. Currently, islet preparations from closely matched donors that are predominant sourced from cadaveric donors are used for transplantation (Edmonton Protocol), and the patients demonstrate independence from insulin for approximately 1 year. However, the problems with this therapeutic regimen are two-fold: (1) requirement for immune-suppression to prevent rejection of the exogenous islets, which also predisposes the patients to chance infections, and (2) short survival period of transplanted islets requiring additional transplantations. As an alternative, patient-specific stem cells are currently being coaxed to mature into beta cells in the dish, which has the advantage of being similar to the host and thereby avoiding the need for long-term immune-suppression. An added advantage is that the manufacturing process is potentially scalable to meet a greater demand. The limitations with this process, however, is that the current protocols only result in beta-cell-like cells and are not fully functional equivalents of the endogenous cells and are not glucose responsive. In this proposal, we plan to approach the problem with a completely novel perspective, which is to leverage a pig model that lacks endogenous islet cells. We plan to seed patient-specific committed stem cells into embryos from these pigs, so that stem cells expand and populate the compartment left vacant, in this case islets from the patients. This approach will provide on-demand source of beta cells that can be transplanted into the host. Another advantage with this model is that the resulting beta cells can be seeded back into the same mutant pig model to test both long-term rescue of the disease and explore optimal sites for transplantation for potential long-term survival. Overall, the submitted proposal is highly innovative and transformative and will revolutionize the patient care.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210017
Entities
People
- Bhanu Telugu
Organizations
- Curators of the University of Missouri
- United States Army