Analysis on Donor and Isolation-Related Factors of Successful Isolation of Human Islet of Langerhans From Human Cadaveric Donors

doi:10.1016/j.transproceed.2005.09.055

Transplantation Proceedings

Volume 37, Issue 8, October 2005, Pages 3402-3403

https://doi.org/10.1016/j.transproceed.2005.09.055 Get rights and content

Abstract

We analyzed the preexisting donor factors and isolation variables that affected isolation of human islets of Langerhans. Sixty-nine pancreata from cadaveric donors were analyzed for donor factors of age, gender, body mass index, cause of death as well as graft factors of cold ischemia time, pancreas status, distensibility during intraductal collagenase distension and time of collagenase expansion and digestion. Islet isolations that recovered >100,000 IEQ (n = 53) were compared to those generating less than 100,000 IEQ (n = 16) to analyze the factors affecting islet yield during donor harvest and isolation procedures. The mean islet recovery was 216.0 × 10³ (IEQ) or 2840 (IEQ) per gram of pancreas. Mean purity was 54%. The success rate of islet isolation was 76%. Mean age was 31 years, and mean cold ischemia time was 6.9 hours. In univariate analysis, the status of the pancreas was the only significant factor for successful isolation, and gender, time of collagenase expansion and digestion were marginal factors. In stepwise multivariate logistic regression analysis of donor and isolation-related factors, donor gender, pancreas status and digestion time were significant factors. During the same period we performed three cases of clinical islet allotransplantation and one autotransplantation. This study confirmed that the same donor factors and variables in the isolation process can affect the ability to obtain successful human islet isolation. Enough experience and pertinent review of donor and isolation factors can make islet isolation consistent, supporting clinical islet transplantation without unnecessary cost.

Section snippets

Cadaveric Donors

Seventy-five cadaveric pancreata were procured for islet isolation after obtaining informed consent from the relatives. Six cases were excluded in the analysis due to technical failures during either the digestion or the purification phases of the islet isolation process. Donor factors reviewed in charts included age, gender, body mass index (weight in kg/height in m²), cause of death (trauma vs nontrauma), cold ischemic time (time from cessation of blood flow to pancreas to time of intraductal

Results

Seventy-five pancreata were procured for isolation of human islets of Langerhans after exclusion of six technical failures. Mean age of donors was 31 years, and mean cold ischemia time was 6.9 hours. Quality control assays on isolated islets were mostly acceptable. The mean islet recovery was 216.0 × 10³ (IEQ) or 2840 (IEQ) per gram of pancreas. Mean purity was 54%. When islet isolation recovered >100,000 IEQ were arbitrarily considered successful, the success rate of islet isolation was 76%.

Discussion

Experience in islet isolations at several center has demonstrated that many factors affect the ability to recover human islets during organ procurement and isolation processes.2, 3, 4 Our center commenced to isolate islets of Langerhans in 1992 as the first center in Korea. It has facilities and techniques according to FDA/c-GMP requirements. Islet yield definitely increased year by year in our center, which showed the importance of experience.

Donor age is one of the important factors affecting

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Cited by (29)

Isolated pancreatic islet yield and quality is inversely related to organ donor age in rats
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Citation Excerpt :
The transplanted islets are obtained from donated cadaveric pancreata that undergo tissue digestion within GMP guidelines (Ricordi et al., 1989). Various factors impact islet quality and isolation yield including the donor's body mass index and cause of death (Kim et al., 2005), and these, in turn, influence clinical outcomes. Fully defining such factors is an important step in islet approval prior to transplantation.
Pancreatic islets consist of several endocrine cell types that maintain glucose homeostasis. Type 1 diabetes (T1D) results from autoimmune-mediated destruction of insulin producing beta cells in pancreatic islets. Islet transplantation is a treatment for certain individuals with T1D. Islet transplantation in rodents, as an experimental model of the clinical scenario, requires consistency of islet quantity and quality to obtain reproducible results. In this study, we investigated the yield and function of the isolated islets from rats of different ages. Pancreata were harvested from young (10–20 week-old), intermediate (21–40 week-old) and old (>41 week-old) male rats and islets were isolated using a standard protocol. Islet number, morphometry, viability, function, and metabolism were characterized. Islet yield, normalized to body weight, decreased as a function of increasing donor age. Islets from pancreata from young animals were larger and less fragmented compared to islets from organs from intermediate and older animals. Islet viability following overnight culture was the same for islets derived from young and intermediate aged donors but less for islets from old donors. Glucose-stimulated insulin secretion was decreased in islets from older donors. Islet metabolism following glucose challenge, as measured by oxygen consumption, revealed that islets from old donors were metabolically slower and lagged in response to glucose-stimuli. These data demonstrate that increasing donor age has a negative impact on isolated islet yield and quality.
Islet product characteristics and factors related to successful human islet transplantation from the collaborative islet transplant registry (CITR) 1999-2010
2014, American Journal of Transplantation
The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×10³ IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.
Usefulness of the secretory unit of islet transplant objects (SUITO) index for evaluation of clinical autologous islet transplantation
2011, Transplantation Proceedings
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These findings are in agreement with those of the University of Cincinnati group, which also demonstrated that female gender and low body weight were associated with insulin independence after autologous islet transplantation.19 It is well known that islet yield is affected by donor factors.20–22 However, gender has not been identified as an influential factor.
Assessing the engrafted islet mass is important in evaluating the efficacy of islet transplantation. We previously demonstrated that the average secretory unit of islet transplant objects (SUITO) index within 1 month of allogeneic islet transplantation was an excellent predictor of insulin independence. However, the usefulness of the SUITO index for evaluating autologous islet transplantation has not been explored. The purpose of the present study was to assess the relationship between the SUITO index and clinical outcomes after total pancreatectomy followed by autologous islet transplantation.
We performed 27 total pancreatectomies followed by autologous islet transplantation from October 2006 to January 2011. Cases were divided into an insulin-independent group (IIG; n = 12) and an insulin-dependent group (lDG; n = 15). The SUITO index was calculated by the formula [fasting C-peptide (ng/mL)/fasting glucose (mg/dL) −63] × 1,500. The average SUITO index within the first month of transplantation except for days 0, 1, and 2, maximum SUITO index, and most recent SUITO index were calculated in each case, and values were compared between the IIG and the IDG.
The average SUITO index within 1 month was significantly higher in the IIG than in the IDG (24.6 ± 3.4 vs 14.9 ± 2.0, respectively; P < .02). The maximum SUITO indices were 45.7 ± 7.7 in the IIG and 30.1 ± 8.1 in the IDG (not significant), and the recent SUITO indices were 36.9 ± 6.7 in the IIG and 22.8 ± 6.1 in the IDG (not significant).
The average SUITO index within 1 month was an excellent predictor of insulin independence after total pancreatectomy followed by autologous islet transplantation.
Multi-Criteria Decision Making support system for pancreatic islet transplantation
2011, Expert Systems with Applications
Citation Excerpt :
Cold ischemia time (CIT) is the duration of time from when the pancreas was placed in cold preservation solution until the warming up of the organ to start the digestion process. Kim et al. (2005) have found no significant influence of CIT in islets yielded, though Lakey et al. (1996) reported significant influence of this factor. We have considered three ranges of values [0–8], [8–12], and [12–20] h, in which a shorter time results in a higher probability of success.
Pancreatic islet transplantation consists of replacing insulin-producing cells to restore normal glycemia in diabetic patients. This is a minimal invasive procedure that has been proved successful. Unfortunately unpredictability of islet transplant outcome remains a frustrating and costly issue limiting the clinical implementation of this procedure. Multiple variables are involved in the procedure and assessment is subjective to individual operators. The aim of this study was to generate a system expressing the probability of transplant success in relation to four classes of identified variables (donor, organ, isolation and recipient). We have proposed the utilization of Multi-Criteria Decision Making methods (MCDM) as a powerful tool for evaluating pancreatic islet transplant-related information with the goal to achieve optimal decision. Technique Ordered Preference by Similarity to the Ideal Solution (TOPSIS), one of the most widely used MCDM methods in decision support systems, was here utilized with modification to fit better in a medical system. In our modified method, we have utilized fuzzy logic in order to consider uncertain and vague data.
Total pancreatectomy with islet autotransplantation: An overview
2009, HPB
Citation Excerpt :
This is largely as a result of the fact that total pancreatectomy, islet isolation and islet transplantation were carried out in the same site. The pancreata are subjected to a minimal period of cold ischaemia in autotransplantation as opposed to those in allotransplantation where the cold ischaemia time can be highly variable and may have a significant effect on the quantity and quality of the islets isolated.39,40 Islet purification does not improve insulin independence in islet autotransplantation.20
Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.
Gender issues in transplantation
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The effects of gender mismatch in clinical transplantation have been recognized for half a century. But gender issues in clinical transplantation affect outcomes at many levels beyond immunologic concerns. Many diseases leading to transplantation are predominantly expressed in one gender. Organ donation patterns have consistently been defined by a greater tendency of women to be live donors. Access to transplantation may be affected by subtleties in the interactions of transplant personnel with women versus men candidates. In the new field of stem-cell transplantation, functional differences in male versus female adult stem cells may shed light on gender differences in outcomes for solid organ transplantation. This review highlights gender issues related to transplantation with a goal of optimizing the care of all transplant patients.

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: This work was supported by grants from the Asan Institute for Life Science (2005-211).

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Clinical practiceIsolation and preservation of human isletAnalysis on Donor and Isolation-Related Factors of Successful Isolation of Human Islet of Langerhans From Human Cadaveric Donors

Abstract

Section snippets

Cadaveric Donors

Results

Discussion

N Engl J Med

Transplantation

Clinical practice
Isolation and preservation of human islet
Analysis on Donor and Isolation-Related Factors of Successful Isolation of Human Islet of Langerhans From Human Cadaveric Donors