The science behind Betalin Theraputics
Islet transplantation has become a feasible cell therapy procedure that aims to achieve normoglycemia in diabetic patients. Currently, one of the greatest challenges in this approach is early islet cell death. The natural microenvironment is lost during islet isolation, resulting in β-cell dysfunction and often death. Therefore, the importance of extracellular matrix (ECM) for islet viability and function has been repeatedly documented. Specifically, interactions between β-cells and the basement membrane of the vasculature are important for correct function. Tissue and organ engineering recognizes the need for a complex supportive stroma and thus several approaches use natural decellularized scaffolds derived from natural tissue or organ.
Thus, Betalin’s Micro Organ Matrix (MOM) technology is a unique 3D biologic scaffold that preserves the complex tissue micro-environment sustaining and improving insulin secretion.This micro-environment together with insulin secreting islets or cells is effectively a micro- organ: Engineered Micro-Pancreas (EMP) that can be also maintained ex vivo, preserving the organ micro-architecture and maintaining the native cell-cell and cell-extra cellular matrix interactions.
Betalin’s series of experiments show improved functional features of EMP1 compared to "naked" islets, validating the EMP proof of concept. Islets function is tested by measuring the levels of insulin secreted after dynamic stimulation with low (LG) and high levels (HG) of glucose.
Indeed, EMPs prepared in our lab with human islets secrete higher levels of insulin than “naked” islets in a glucose- regulated manner.Moreover, EMPs continue to secrete quantities of insulin similar to freshly isolated human islets (day 0) in a glucose- regulated manner for more than three months, while “naked” islets survive less than 7 days with constantly decreasing functionality.
Following promising pre-clinical animal studies, we report reversal of diabetes in mice by subcutaneous transplantation of EMPs with a human islet dose as low as 500 IEQ.
Diabetic mice receiving subcutaneous transplant of EMPs, with a human islet dose of 500 IEQ, were normoglycemic throughout the study period. At 35 days post-transplantation, upon retrieval of the implanted EMPs, the mice reverted to hyperglycemia (see graph below). In contrast, the controlanimals, which did not receive EMP transplants, had high blood glucose levels that increased rapidly causing hyperglycemia and leading to animals’ death within 5 to 8 days.Thus, our proof of concept of the EMP was pre-clinically validated, facilitating diabetes reversal in a mouse animal model.These exciting findings lay the foundation for Betalin Therapeutics' solution and are the basis of development towards clinical application.
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