Isolation and Characterization of Mesenchymal Stromal Cells from the Visceral Adipose Tissue in Peripancreatic Region
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".