Process parameter development for the scaled generation of stem cell‐derived pancreatic endocrine cells

Autor: Iworima, Diepiriye G., Rieck, Sebastian, Kieffer, Timothy J.
Zdroj: Stem Cells Translational Medicine; November 2021, Vol. 10 Issue: 11 p1459-1469, 11p
Abstrakt: Diabetes is a debilitating disease characterized by high blood glucose levels. The global prevalence of this disease has been projected to reach 700 million adults by the year 2045. Type 1 diabetes represents about 10% of the reported cases of diabetes. Although islet transplantation can be a highly effective method to treat type 1 diabetes, its widespread application is limited by the paucity of cadaveric donor islets. The use of pluripotent stem cells as an unlimited cell source to generate insulin‐producing cells for implant is a promising alternative for treating diabetes. However, to be clinically relevant, it is necessary to manufacture these stem cell‐derived cells at sufficient scales. Significant advances have been made in differentiation protocols used to generate stem cell‐derived cells capable of reversing diabetes in animal models and for testing in clinical trials. We discuss the potential of both stem cell‐derived pancreatic progenitors and more matured insulin‐producing cells to treat diabetes. We discuss the need for rigorous bioprocess parameter optimization and identify some critical process parameters and strategies that may influence the critical quality attributes of the cells with the goal of facilitating scalable manufacturing of human pluripotent stem cell‐derived pancreatic endocrine cells. Donor islet transplantation can effectively reverse hyperglycemia in people living with type 1 diabetes. However, there is a limited supply of replacement donor islets. Human pluripotent stem cells are a renewable source of starting material that could overcome the supply challenges associated with islet transplantation. Pluripotent stem cells can be expanded at large scale, differentiated into islet‐like clusters, and cryopreserved prior to implant into patients.
Databáze: Supplemental Index