Research Projects

Rationale Diabetic patients are more prone to infections due to immune dysregulation and vascular complications. These infections eventually become systemic, leading to sepsis. As a consequence, large number of diabetic patients die due to sepsis-based complications. In the quest of alternative or adjuvant therapies to treat diabetic patients, we shortlisted mesenchymal stromal cells (MSCs) as potential contenders. MSCs have well established role in immune modulation, anti-microbial activities and regeneration as evident by numerous studies. Moreover, we propose to engineer these MSCs by preconditioning them with Curcumin. Curcumin is a polyphenol extracted from the root of Curcuma Longa L and has been used to treat inflammatory disease for many decades. An appropriate preconditioning can EMPOWER the survivability of MSCs by upregulating their antioxidative, anti-inflammatory, and anti-apoptotic properties. Consequently, using these licensed stem cells may improve the anticipated therapeutic outcomes of stem-cell based interventions. Research Question Can we design an efficient therapeutic intervention by harnessing the combined properties of MSCs & curcumin and test the efficacy of this novel therapy in a sepsis model of diabetes? Hypothesis: Synergistic action of UC-MSCs & curcumin can be a potential alternative therapeutic option for treatment of diabetes induced sepsis. Following are the objectives designed in order to execute our aim of the proposal: 1. Preconditioning umbilical cord derived mesenchymal stromal cells (UC-MSCs) with hydro soluble curcumin and analyze the molecular signatures at the transcriptome level. 2. Treating septic diabetic mice with licensed UC-MSCs/conditioned medium. 3. Analysing functional consequence of this treatment in terms of molecular signatures and alleviating sepsis induced complications. Methodology • Isolation of human UC MSCs • Preconditioning UC MSCs • Transcriptomic analysis of primed UC MSCs • Developing diabetic sepsis mouse model • Infusion of UC MSCs in sepsis model of diabetes • Bacterial clearance Sepsis markers analysis post UC MSC infusion • Transcriptomic analysis of peripheral blood cells, liver, spleen, kidney to analyze molecular signatures post licensed MSC infusion. Proposed outcome/Significance Considering the significantly high burden of diabetes and diabetes induced sepsis, there is a pressing need to develop alternative or supportive treatment regimens as the current treatments are not completely effective. • The synergistic approach of the proposed project is highly significant in developing an innovative & efficient therapeutic system by harnessing the properties of both MSCs & curcumin and test the efficacy in a preclinical diabetes induced sepsis model as a primary outcome. • The outcome of the project has direct translational value in improvisation of existing therapies to treat diabetic patients especially developing sepsis as a secondary outcome of the disease.