Biyoyapay Pankreas: Pankreas Hücrelerinin Enkapsülasyonu ile Hücre Tedavileri

Abstract

Type 1 Diabetic (T1D) Disease, a type of the diabetic diseases, caused by the destruction of the pancreatic beta cells caused by autoimmune and non-immune mechanisms is an autoimmune illness and conventionally exogenous insulin is applied for treatment. Inefficient blood glucose level fluctuation control leads to secondary complications during this treatment such as; retinopaty, neuropaty, nefropaty and cardiovascular diseases. Instead of lifelong insulin usage, pancreas implantation emerges as another option for diabetes treatment. However, pancreas transplantation is not utilized as primary treatment choice, because of difficulties in finding donors, heavy surgical operations and troublesome immune suppression procedure. In spite of the fact that transplantation of islet cells instead of whole pancreas can be achieved by relatively smaller surgical operations, immune suppression procedure is still required. Encapsulation of islet cells with the help of improved nanotechnological methods provides them with immunoisolation, long duration of viability and functionality. Islet cell encapsulation techniques can be classified as micro or nanoencapsulation regarding the thickness of the membrane. Primary drawback after encapsulation is that encapsulated cells are not supplied with the sufficient amount of oxygen and nutrient. Macroencapsulated islet cells cannot survive for a long time because of increased distance between cells and encapsulation surface. Nano thickness encapsulation minimizes this distance and increases the possible implantation sites of the encapsulated cells as well. Within the scope of this thesis study, bioartificial pancreas model formation was targeted by applying combination of self-assembled peptides, such as fluorenyl-9-methoxycarbonyl-diphenylalanine/arginine-glycine-aspartate (Fmoc-FF/Fmoc-RGD), and multilayered alginate-GRGDSP/chitosan encapsulation method. After nanofilm multilayered islet cell encapsulation with alginate-GRGDSP/chitosan was verified by TEM images (less than 100 nm), nanoencapsulated cells were analyzed in terms of their insulin secreting modality and survival in vitro. As they were found to demonstrate physiologically similar properties, in vivo rat islet transplantation pre-study was conducted thereafter. In consequence of in vivo studies, no difference were found between nanoencapsulated islet cells implanted rats and control group regarding normoglycemia maintaining time.