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Progression to Fragmentation during Cellular Isolation Improves Clinical Glycemic Outcomes in Patients Undergoing Islet Cell Transplantation

Timothy B. Gardner*, Steven M. Hadley, Kerrington D. Smith, Sushela S. Chaidarun, Dawn A. Fischer

Context Islet autotransplantation (IAT) involves a complex islet isolation process in which the explanted pancreas is mechanically and enzymatically digested to separate islet cells from exocrine pancreatic tissue. Islet cells transition during the isolation process from being “embedded” in exocrine pancreatic tissue, to becoming “free” once separated from the exocrine tissue, to eventually becoming “fragmented” with ongoing digestion. However, it is unclear if the relative percentage of “embedded”, “free” or “fragmented” islet cells affects subsequent pancreatic endocrine function. Objective Evaluate the effect of each type of islet cell on endocrine function in patients who underwent IAT. Design Retrospective cohort study. Setting Academic tertiary medical center Patients 33 patients who underwent IAT from 2015-2020. Main Outcome Measures Percent change in pre-operative vs. three month post-operative c-peptide levels. Results There was a weak correlation between the percent change in c-peptide and number of “fragments” (R2=0.0156) and percent of islet cells ‘embedded” (R2=0.0011). However, as the number of “fragments” increased and percent “embedded” decreased, the percent change in C-peptide approached zero. Genetic etiologies (CFTR, SPINK1, PRSS1, CTCR, and CPA1) resulted in lower percent decreases in c-peptide than non-genetic etiologies (9% vs. 52%, p=0.152) although this trend did not reach statistical significance. Conclusion Although a weak correlation existed between the number of “fragments” and the percent change in c-peptide, the data support erring on the side of allowing the digestion to proceed to more “fragments” and fewer “embedded” islets in order to enhance glycemic outcomes. As such, we suggest stopping digestion when no more “embedded” islets are observed.

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