A total pancreatectomy and islet autotransplant (TPIAT) offers substantial pain relief and improved quality of life for pancreatitis patients. Isolating a large quantity of islet cells from chronic pancreatitis pancreas (CPP) is critical for achieving long-term insulin independence after transplantation. It is difficult to obtain high islet mass from fibrotic CPP. In our laboratory, we developed improved islet isolation techniques to obtain a high islet yield, even from severely fibrotic CPP. This modified islet isolation processes were tested first with donor research pancreases (n=25) and included 1) Adjusting the collagenase enzyme blend (CEB) doses based on severity of fibrosis instead of using the standard one vial/pancreas approach. 2) Adequate/prolonged delivery of tissue dissociation enzyme throughout the pancreas by using both intraductal and parenchymal injection methods, and 3) Early collection and warm recirculation of CEB if digestion time is prolonged for >minutes. We transplanted the results of this study in to our clinical isolation.

As part of our clinical program, 12 patients have undergone a total pancreatectomy with an islet autotransplant at the Jewish Hospital/University of Louisville. Etiology of chronic pancreatitis (CP) was associated with alcoholism (n=7); idiopathic (n=3); gall stone (n=1); and pancreas divisum (n=1). Following pancreatectomy, the pancreas was transported with UW solution and brought to a cGMP clean room facility for processing. The pancreas was cannulated and manually distended with CEB solution intraductally. The enzyme mixture consisted of CIzyme collagenase (VitaCyte) and Neutral Protease (SERVA). The enzyme dose was adjusted according to the severity of fibrosis. The final islet product was evaluated for sterility and islet viability was assessed by FDA/PI.

Using our modified islet isolation techniques, we digested >90% of the pancreases. The average tissue volume obtained at digest level was 10±8.6cc. The average transplanted islet mass was 5,033±656 IEQ/kg and the average IEQ/gram pancreas was 4,383±1264. The average infused tissue volume was 9±6.5cc. Our results indicated that it is possible to obtain >4,000 IEQ/gram even from severely CPP. This study demonstrates that multiple approaches may be necessary to digest fibrotic pancreases.

CITATION INFORMATION: Balamurugan A, Loganathan G, Tucker W, Dhanasekaran M, Narayanan S, Patel A, Mokshagundam S, Williams S, Hughes M. Improved Method to Obtain High Islet Mass from Severely Fibrotic Pancreatitis Pancreases Intended for Clinical Islet Auto-Transplantation. Am J Transplant. 2017;17 (suppl 3).

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