Adipose derived mesenchymal stem cell exosomes for ß cell protection and regeneration

​The project will apply a multidisciplinary approach combining studies in cellular and animal models to investigate if ''cell free'' purified AD-MSCs exosome treatment can protect and regenerate ß cell.

Type 1 diabetes (T1D) disease is characterized by destruction of ß cells. However, studies have shown that patients still have residual ß cell mass and activity years after diagnosis. Hence, developing therapeutic approaches for maintaining, recovering or regenerating ß cell mass within the pancreas of T1D patients is of paramount importance. 

One promising approach is the use of mesenchymal stem cells (MSCs) that have been successfully used for regenerative purposes in the other diseases. However, the clinical translation of MSC therapy for treatment of T1D has been sub-optimal, predominantly due to the inability of MSCs to reach the pancreas. Moreover, evidence suggests that the potential therapeutic effect of MSCs is mostly mediated by releasing broad spectrum of autocrine and paracrine factors mainly constrained in extracellular vesicles (EVs). 

An important sub-group of EVs are exosomes, which most likely are the principal mediators underlying the therapeutic effect of MSCs. Therefore, to investigate the therapeutic effect of exosomes on protecting and regenerating ß cells and subsequent glycemic regulation, in this study, using an innovative novel technology I will purify exosomes and in a “cell-free” approach for the first time, deliver them to the rat diabetic pancreas by a newly developed intra-arterial controllable delivery technique. I will further investigate the molecular mechanisms by which exosomes exert their therapeutic effects on ß cells in cell culture.

Aim

To investigate the therapeutic effect of AD-MCs exosomes on protecting and regenerating damaged β cells using cellular and rat models of T1D.

Collaborators

Avnesh S Thakor, Stanford Bio-X, Stanford university medical center, USA.
Utkan Demirci, Stanford Bio-X, Canary cancer center, USA.

Funding

The Lundbeck Foundation - R303-2018-3148









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