Betazellersatz und Stammzelltherapie des Diabetes – Wo stehen wir heute?

Patienten mit autoimmunem Typ-1-Diabetes sind nach Ausbruch der Erkrankung lebenslang auf exogene Insulingaben angewiesen. Trotz guter Insulineinstellung entstehen häufig schwerwiegende diabetische Langzeitkomplikationen. Dies zeigt, dass exogene Insulingaben den Blutzucker nicht so exakt regulieren können wie Insulin produzierende Betazellen. Die Wiederherstellung der endogenen Betazellen ist daher ein wichtiges therapeutisches Ziel. Klinisch etabliert sind Pankreas- und Inseltransplantation, deren Anwendung allerdings durch die notwendige Immunsuppression und den Mangel an Spenderorganen limitiert ist. Stammzellen vermehren sich in vitro ohne die Fähigkeit zu verlieren, sich in andere Zelltypen zu differenzieren. Die Forschung versucht diese Fähigkeit für die Generierung von Surrogatbetazellen für die Inseltransplantation zu nutzen. Adulte mesenchymale Knochenmarksstammzellen (MSC) besitzen zusätzlich immunmodulatorische, proangiogene und regenerative Eigenschaften, welche über humorale Faktoren und Interaktionen mit regulatorischen T-Zellen vermittelt werden. MSC können daher im Tiermodell Inseltransplantatabstoßung inhibieren, Typ-1-Diabetes mildern und eine diabetisch geschädigte Betazellmasse regenerieren. Dieser Übersichtsartikel erläutert den aktuellen Stand der Forschung und die verbleibenden Probleme, die einem klinischen Einsatz von Stammzelltherapien derzeit noch im Wege stehen.

After onset of the disease, patients with autoimmune Type 1 diabetes depend on lifelong administration of exogenous insulin. Even if patients are well adjusted, they frequently develop severe late-diabetic complications. This indicates that exogenous insulin application cannot completely mimic the exact regulation of normoglycemia by pancreatic beta cells. Restoration of endogenous beta cell mass is therefore an important therapeutical goal which is currently achieved by pancreas and islet transplantation. However, both therapies are limited by the need for immunesuppression and lack of suitable donor material. Stem cells expand in vitro without losing their capacity to differentiate into other cell types. Researchers try to exploit this potential for the generation of surrogate beta cells for use in clinical islet transplantation. Alternatively, adult bone marrow-derived mesenchymal stem cells (MSC) provide immunomodulatory, proangiogenic and regenerative features that are mediated via humoral factors or interactions with regulatory T cells. MSC have been shown in animal models to reduce islet graft rejection, to ameliorate type 1 diabetes and to regenerate a diabetically degraded beta cell mass. This review displays the status quo of research and comments on the existing difficulties that still constrain translation of current cell therapeutic approaches into clinical praxis.

Key words

Diabetes - beta cell - transplantation - stem cell therapy

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