Beta Cell Replacement
Diabetes mellitus is one of the most prevalent metabolic diseases worldwide and is characterized by insulin deficiency that is caused by dysfunction or destruction of insulin-producing beta cells in the islet of Langerhans. Daily insulin administrations saves the life of type 1 diabetic patients, however these patients still suffer from fluctuating blood glucose levels that bear the risk of hypoglycemia, lifelong secondary complications and a shortened life span. Importantly, upon transplantation of cadaveric human islets, patients achieve normoglycemia, however compatible human islets are scarce. Human pluripotent stem cells (hPSCs) serve as an optimal source - due to their self-renewing capacity and potency to differentiate into all cell lineages - to generate endocrine islet cells, such as beta cells, in vitro for cell replacement therapy.
For this reason, the transplantation of stem cell-derived human islets (SC-islets) hold great promise to cure diabetes. Although the efficiency of recent in vitro differentiation protocols improved, the SC-islets consist of not only endocrine cells but also unwanted non-endocrine cell types that impair functionality of SC-islets and safety for patients. We are specifically interested to develop new approaches to generate advanced SC-islets with improved functionality that eventually permits their transplantation into type 1 diabetic patients.
Moreover, the molecular mechanisms of human pancreas development, such as the induction and patterning of the endoderm and the foregut as well as the induction of an endocrine fate, are not fully resolved. In vitro differentiation of hPSCs allows us to study these developmental processes in more detail. Therefore, another interest of our group is to unravel these mechanisms and thereby improve in vitro differentiation protocols for cell replacement therapy.
Diabetes mellitus is one of the most prevalent metabolic diseases worldwide and is characterized by insulin deficiency that is caused by dysfunction or destruction of insulin-producing beta cells in the islet of Langerhans. Daily insulin administrations saves the life of type 1 diabetic patients, however these patients still suffer from fluctuating blood glucose levels that bear the risk of hypoglycemia, lifelong secondary complications and a shortened life span. Importantly, upon transplantation of cadaveric human islets, patients achieve normoglycemia, however compatible human islets are scarce. Human pluripotent stem cells (hPSCs) serve as an optimal source - due to their self-renewing capacity and potency to differentiate into all cell lineages - to generate endocrine islet cells, such as beta cells, in vitro for cell replacement therapy.
For this reason, the transplantation of stem cell-derived human islets (SC-islets) hold great promise to cure diabetes. Although the efficiency of recent in vitro differentiation protocols improved, the SC-islets consist of not only endocrine cells but also unwanted non-endocrine cell types that impair functionality of SC-islets and safety for patients. We are specifically interested to develop new approaches to generate advanced SC-islets with improved functionality that eventually permits their transplantation into type 1 diabetic patients.
Moreover, the molecular mechanisms of human pancreas development, such as the induction and patterning of the endoderm and the foregut as well as the induction of an endocrine fate, are not fully resolved. In vitro differentiation of hPSCs allows us to study these developmental processes in more detail. Therefore, another interest of our group is to unravel these mechanisms and thereby improve in vitro differentiation protocols for cell replacement therapy.
Research Topics
Helmholtz Munich - Eunike SetyonoEunike Setyono, PhD student
Despite improvement in beta cell differentiation protocols, most protocols still generate a mixture of cells containing endocrine cells along with progenitor and other cell types. These impurities could lead to reduction in functionality as well as potential teratoma source upon transplantation. My project aims to improve the functionality and maturity of SC-islets through enrichment of SC-alpha and beta cells as well as depletion of unwanted cell types. Additionally, I am interested in studying the induction and patterning of gut endoderm with the aim to improve the differentiation protocol towards SC-islets.
Helmholtz Munich | Nicole RogersNicole Rogers, PhD student
My project aims is to characterize the undefined cell types, which arise in the β-cell differentiation protocols and to use this knowledge to increase protocol efficiency. Another part of my project is to pre-vascularise the SC-ILCs improving graft outcome as well as study their maturation and their ability to restore normoglycemia in diabetic mice.
Helmholtz Munich - Eunike SetyonoEunike Setyono, PhD student
Despite improvement in beta cell differentiation protocols, most protocols still generate a mixture of cells containing endocrine cells along with progenitor and other cell types. These impurities could lead to reduction in functionality as well as potential teratoma source upon transplantation. My project aims to improve the functionality and maturity of SC-islets through enrichment of SC-alpha and beta cells as well as depletion of unwanted cell types. Additionally, I am interested in studying the induction and patterning of gut endoderm with the aim to improve the differentiation protocol towards SC-islets.
Helmholtz Munich | Nicole RogersNicole Rogers, PhD student
My project aims is to characterize the undefined cell types, which arise in the β-cell differentiation protocols and to use this knowledge to increase protocol efficiency. Another part of my project is to pre-vascularise the SC-ILCs improving graft outcome as well as study their maturation and their ability to restore normoglycemia in diabetic mice.
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