Use of culture to reach metabolically adequate beta cell dose by combining donor islet cell isolates for transplantation in type 1 diabetes patients
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BACKGROUND: Clinical islet transplantation is generally conducted within 72 hours after isolating sufficient beta cell mass. A preparation that does not meet the sufficient dose can be cultured until this is reached after combination with subsequent ones. This retrospective study examines whether metabolic outcome is influenced by culture duration.
METHOD: Forty type 1 diabetes recipients of intraportal islet cell grafts under ATG induction and MMF-Tacrolimus maintenance immunosuppression were analysed. One subgroup (n=10) was transplanted with preparations cultured for ≥96hours; in the other subgroup (n=30) grafts contained similar beta cell numbers but included isolates that were cultured for a shorter duration. Both subgroups were compared by numbers with plasma C-peptide≥0.5ng/ml, low glycemic variability associated with C-peptide≥1.0ng/ml, and/or with insulin independence.
RESULTS: The subgroup with all cells cultured ≥96hours exhibited longer C-peptide≥0.5ng/ml (103 versus 48 months, P=0.006), and more patients with low glycemic variability and C-peptide≥1.0ng/ml, at month 12(9/10 vs. 12/30; P=0.005) and 24(7/10 vs. 6/30; P=0.007). In addition, 9/10 became insulin-independent versus 15/30 (P=0.03). Grafts with all cells cultured ≥96 hours did not contain more beta cells but a higher endocrine purity (49% versus 36%, P=0.03). In multivariate analysis, longer culture duration and older recipient age were independently associated with longer graft function.
CONCLUSIONS: Human islet isolates with insufficient beta cell mass for implantation within 72 hours can be cultured for 96 hours and longer to combine multiple preparations in orde to reach the desired beta cell dose and therefore result in a better metabolic benefit.