Suitability of human juvenile pancreatic islets for clinical use

Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity as possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme used to dissociate the pancreas is a critical determinant of islet yield, which is correlated with posttransplant function. Here, we present our experience with IAT procedures to compare islet product data using the new enzyme SERVA/Nordmark (SN group; n = 46) with the standard enzyme Liberase-HI (LH group; n = 40). Total islet yields (mean ± standard deviation; 216 417 ± 79 278 islet equivalent [IEQ] in the LH group; 227 958 ± 58 544 IEQ in the SN group; p = 0.67) were similar. However, the percentage of embedded islets is higher in the SN group compared to the LH group. Significant differences were found in pancreas digestion time, dilution time, and digested pancreas weight between the two groups. Multivariate linear regression analysis showed the two groups differed in portal venous pressure changes. The incidence of graft function and insulin independence was not different between the two groups. The SN and LH enzymes are associated with similar outcomes for IAT. Further optimization of the collagenase/neutral protease ratio is necessary to reduce the number of embedded islets obtained when using the SN enzyme.

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“…(27,28), donor BMI (23), islet isolation technique (28) and type of enzyme used for pancreas dissociation (13,26 …”

Section: We Have Successfully Utilized the New Enzyme Sn For Autologomentioning

confidence: 99%

Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche Enzymes

Anazawa

Balamurugan

Bellin

et al. 2009

American Journal of Transplantation

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“…19 Pancreata from younger donors (<15 years old) would still remain a challenge to isolate free islets despite attempts that were made to obtain highly purified islets from donors with certain age range (6 months to 17 yrs). 51,52 In fact, the pancreata from younger donors with lower BMI yield less tissue volume and therefore, digested tissues could be transplanted into type 1 diabetic patients without purification. Transplanting tissues from younger donors without purification might have a great advantage because of the potential for islet regeneration, particularly if transplanted into the omentum.…”

Section: Discussionmentioning

confidence: 99%

The Choice of Enzyme for Human Pancreas Digestion Is a Critical Factor for Increasing the Success of Islet Isolation

Valiente

McFadden

et al. 2015

Transplantation Direct

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Background We evaluated three commercially available enzymes for pancreatic digestion by comparing key parameters during the islet isolation process, as well as islet quality post-isolation. Methods Retrospectively compared and analyzed islet isolations from pancreata using three different enzyme groups: Liberase HI (n=63), Collagenase NB1/Neutral Protease (NP) (n=43), and Liberase Mammalian Tissue Free Collagenase/Thermolysin (MTF C/T) (n=115). A standardized islet isolation and purification method was used. Islet quality assessment was carried out using islet count, viability, in vitro glucose-stimulated insulin secretion (GSIS), glucose-stimulated oxygen consumption rate (ΔOCR), and in vivo transplantation model in mice. Results Donor characteristics were not significantly different among the three enzyme groups used in terms of age, sex, hospital stay duration, cause of death, body mass index (BMI), hemoglobin A1c (HbA1c), cold ischemia time (CIT), and pancreas weight. Digestion efficacy (percentage of digested tissue by weight) was significantly higher in the Liberase MTF C/T group (73.5 ± 1.5 %) when compared to the Liberase HI group (63.6 ± 2.3 %) (p<0.001) and the Collagenase NB1/NP group (61.7 ± 2.9%) (p<0.001). The stimulation index for GSIS was significantly higher in the Liberase MTF C/T group (5.3 ± 0.5) as compared to the Liberase HI (2.9 ± 0.2) (p<0.0001) and the Collagenase NB1/NP (3.6 ± 2.9) (p=0.012) groups. Furthermore, the Liberase MTF C/T enzymes showed the highest success rate of transplantation in diabetic NOD Scid mice (65%), which was significantly higher than the Liberase HI (42%, p=0.001) and the Collagenase NB1/NP enzymes (41%, p<0.001). Conclusions Liberase MTF C/T is superior to Liberase HI and Collagenase NB1/NP in terms of digestion efficacy and glucose-stimulated insulin secretion in vitro. Moreover, Liberase MTF C/T had a significantly higher success rate of transplantation in diabetic NOD Scid mice compared to Liberase HI and Collagenase NB1/NP enzymes.

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“…17, 27,28,29 For the pediatric pancreata, we currently use a new enzyme mixture that consists of a higher proportion of intact C1:C2 Clostridium histolyticum (Ch) collagenase and Ch neutral protease. The new enzyme mixture improved islet yields in pediatric pancreata without compromising their functional capacity in vivo.…”

Section: Islet Isolationmentioning

confidence: 99%

Total Pancreatectomy and Islet Autotransplantation in Children for Chronic Pancreatitis

et al. 2014

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Objective Describe the surgical technique, complications and long term outcomes of total pancreatectomy and islet auto transplantation (TP-IAT) in a large series of pediatric patients. Summary Background Data Surgical management of childhood pancreatitis is not clear; partial resection or drainage procedures often provide transient pain relief, but long term recurrence is common due to the diffuse involvement of the pancreas. Total pancreatectomy (TP) removes the source of the pain, while islet auto transplantation (IAT) potentially can prevent or minimize TP-related diabetes. Methods Retrospective review of 75 children undergoing TP-IAT for chronic pancreatitis who had failed medical, endoscopic or surgical treatment between 1989–2012. Results Pancreatitis pain and the severity of pain statistically improved in 90% of patients after TP-IAT (p =<0.001). The relief from narcotics was sustained. Of the 75 patients undergoing TP-IAT, 31 (41.3%) achieved insulin independence. Younger age (p=0.032), lack of prior Puestow (p=0.018), lower body surface area (p=0.048), IEQ per Kg Body Weight (p=0.001) and total IEQ (100,000) (0.004) were associated with insulin independence. By multivariate analysis, 3 factors were associated with insulin independence after TP-IAT:(1) male gender, (2) lower body surface area and the (3) higher total IEQ per kilogram body weight. Total IEQ (100,000) was the single factor most strongly associated with insulin independence (OR = 2.62; p value < 0.001). Conclusions TP-IAT provides sustained pain relief and improved quality of life. The β cell function is dependent on islet yield. TP-IAT is an effective therapy for children with painful pancreatitis that fail medical and or endoscopic management

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Suitability of human juvenile pancreatic islets for clinical use

Cited by 66 publications

References 38 publications

Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche Enzymes

Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche Enzymes

The Choice of Enzyme for Human Pancreas Digestion Is a Critical Factor for Increasing the Success of Islet Isolation

Total Pancreatectomy and Islet Autotransplantation in Children for Chronic Pancreatitis

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