Isolation and Characterization of Mesenchymal Stromal Cells from the Visceral Adipose Tissue in Peripancreatic Region

• Author / Creator

  Osmanmyrat Hojanepesov

• Type 1 Diabetes Mellitus (T1DM) is a multigenic autoimmune disorder that leads to the destruction of insulin producing β-cells of the pancreas by the host immune system. This can lead to chronic hyperglycemia, diabetic ketoacidosis (DKA), retinopathy, nephropathy, neuropathy, serious cardiovascular complications, severe hypoglycemic unawareness and glucose instability. Conventional management therapy includes daily glucose monitoring and exogenous insulin injections. Islet transplantation is an attractive alternative to conventional therapy. First attempts of islet transplantation dates to 1972. Clinical feasibility and efficacy of islet transplantation was first demonstrated by Edmonton protocol (EP) developed by the Islet Transplant Group in Edmonton in 2000. However, some of the limitations of this approach include limited islet supply, gradual graft loss, and harmful chronic immunosuppression regimen. Even with marked improvements, at its current state, the procedure it is reserved for specific subset of T1DM patients that have unstable T1DM and hypoglycemia unawareness, severe hypoglycemic episodes and glycemic lability that cannot be controlled with intensive insulin therapies.
  Some of the major limitations of islet transplantation that need to be overcome for it to be widely available are limited islet supply, chronic immunosuppression to prevent allograft rejection, and gradual graft loss. The last two could be potentially be addressed with Mesenchymal Stromal Cells (MSCs) which are multipotent stem cells found in the stroma of most of the tissues in the body. These cells have self-renewal capacity and can be differentiate into adipocytes, osteoblasts, and chondrocytes. MSCs can suppress the inflammation and promote tissue repair and regeneration through the secretion of cytokines, anti-oxidants, pro-angiogenic factors, anti-apoptotic factors, antimicrobial factors, and trophic molecules.
  Current literature suggests that there are source-dependent differences in MSCs with respect to cell yield per mass of tissue, transcriptome and secretome profiles, and proliferative and mitotic capacities. This thesis examined the ideas of microenvironment-dependent differences among different types of MSCs and that MSCs that are ontologically and anatomically closer to the islets might be more beneficial to them. Therefore, in this study we isolated and characterized cells from the visceral adipose tissue specifically in the peripancreatic region. In accordance with International Society for Cellular Therapy (ISCT), my data demonstrate that cells I prepared attached to the plastic, expressed a MSC-defining cell surface markers, and differentiated into adipocytes but not chondroblasts and osteoblasts. Reduced differentiation potential could be explained by the fact that the donors were elderly and obese, and the cells have undergone many mitotic divisions before undergoing differentiation protocols. Given the results from multiply analyses we denoted them as ppaMSCs. This newly characterized cells could be used in the future studies to assess their effects in islets transplantation.

• Subjects / Keywords

  • Stem cells

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-7sqk-m590

• License

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