Harnessing the secretome of adipose-derived stromal cells to engineer an optimal subcutaneous site for pancreatic islet transplantation

Replacement of the deficient insulin-producing cells by healthy ones is a promising treatment for Type 1 Diabetes (T1D). However, no transplantation site in the human body adequately supports the long-term survival of the newly transplanted cells. Biomaterials can be used to develop a device that can be easily implanted under the skin and in which an optimal microenvironment can be created. In this thesis, an innovative approach using the bioactive molecules secreted by fat-derived stem cells (secretome) was investigated to optimize the microenvironment within a biomaterial device. The study elucidated the composition of secretomes resulting from diverse culturing conditions, including exposure to different oxygen levels, cytokines, and glucose. The experiments showed that each secretome has its special ability to kickstart the body's regenerative processes, like building new blood vessels and changing the surrounding tissue's structure, especially by adding collagen and controlling the immune system. Also, researchers tested how well devices loaded with these secretomes could blend with the body using an animal model. Devices filled with secretomes of cells grown in low oxygen and high glucose conditions showed better growth of blood vessels and more of the surrounding tissue structure after being under the skin for 21 days. When insulin-producing cells were transplanted into these devices, preliminary data suggested that the recipients showed better tolerance to glucose and response to insulin. The findings provide insight into using fat-derived stem cell secretomes to improve insulin-producing cell transplantation outcomes as T1D treatment.