Horm Metab Res 2011; 43(2): 92-99
DOI: 10.1055/s-0030-1270451
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Presence of Hyperemic Islets in Human Donor-Pancreata Results in Reduced Islet Isolation Yield

D. E. Hilling1 , H. A. M. Töns1 , P. J. Marang-van de Mheen2 , A. G. Baranski1 , E. K. van den Akker1 , O. T. Terpstra1 , E. Bouwman1
  • 1Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
  • 2Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands
Further Information

Publication History

received 30.08.2010

accepted 02.12.2010

Publication Date:
13 January 2011 (online)

Abstract

When studying histological characteristics of human donor-pancreata, a remarkably high number of hyperemic islets (HIs) were encountered. The abnormalities in these HIs ranged from single/multiple dilated vessels to hemorrhages extending into the exocrine tissue. We aimed to determine the relevance of the presence of HIs in human donor-pancreata for isolation outcome and to identify donor and procurement factors associated with the occurrence of HIs. The presence of HIs was scored semi-quantitatively (HI−, HI+) in 102 human donor-pancreata. Islet isolation was performed in 40 cases. Donor and procurement factors were retrospectively analyzed in 94 donors. HIs were found in 54.6% of all donor-pancreata. However, only 4.5% of all islets in the affected pancreata was hyperemic. The affected pancreata contained slightly more endocrine tissue, but produced significantly lower yields. When corrected for other factors known to influence isolation outcome, the presence of HIs and endocrine content were the only factors significantly influencing isolation outcome. Prolonged ICU stay and pre-procurement hypertension were associated with the presence of HIs. This study is a first indication that the presence of HIs in human donor-pancreata are associated with reduced isolation outcomes and suggest an impact of the procurement procedure and pre-procurement hemodynamic status of the donor on the islet quality. It is tempting to speculate that this contributes to the generally experienced difficulties in obtaining sufficient amounts of human islets.

References

  • 1 Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.  N Engl J Med. 2000;  343 230-238
  • 2 Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation.  Diabetes. 2005;  54 2060-2069
  • 3 Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, Pileggi A, Poggioli R, Ichii H, Khan A, Ferreira JV, Pugliese A, Esquenazi VV, Kenyon NS, Alejandro R. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience.  Am J Transplant. 2005;  5 2037-2046
  • 4 Ricordi C, Inverardi L, Kenyon NS, Goss J, Bertuzzi F, Alejandro R. Requirements for success in clinical islet transplantation.  Transplantation. 2005;  79 1298-1300
  • 5 Shapiro AM, Ricordi C. Unraveling the secrets of single donor success in islet transplantation.  Am J Transplant. 2004;  4 295-298
  • 6 Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, Matsumoto I, Ihm SH, Zhang HJ, Parkey J, Hunter DW, Sutherland DE. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes.  JAMA. 2005;  293 830-835
  • 7 Markmann JF, Deng S, Huang X, Desai NM, Velidedeoglu EH, Lui C, Frank A, Markmann E, Palanjian M, Brayman K, Wolf B, Bell E, Vitamaniuk M, Doliba N, Matschinsky F, Barker CF, Naji A. Insulin independence following isolated islet transplantation and single islet infusions.  Ann Surg. 2003;  237 741-749
  • 8 van Deijnen JH, Hulstaert CE, Wolters GH, van Schilfgaarde R. Significance of the peri-insular extracellular matrix for islet isolation from the pancreas of rat, dog, pig, and man.  Cell Tissue Res. 1992;  267 139-146
  • 9 van Deijnen JH, van Suylichem PT, Wolters GH, van Schilfgaarde R. Distribution of collagens type I, type III and type V in the pancreas of rat, dog, pig and man.  Cell Tissue Res. 1994;  277 115-121
  • 10 van Suylichem PT, van Deijnen JE, Wolters GH, van Schilfgaarde R. Amount and distribution of collagen in pancreatic tissue of different species in the perspective of islet isolation procedures.  Cell Transplant. 1995;  4 609-614
  • 11 Hughes SJ, McShane P, Contractor HH, Gray DW, Clark A, Johnson PR. Comparison of the collagen VI content within the islet-exocrine interface of the head, body, and tail regions of the human pancreas.  Transplant Proc. 2005;  37 3444-3445
  • 12 Hughes SJ, Clark A, McShane P, Contractor HH, Gray DW, Johnson PR. Characterisation of collagen VI within the islet-exocrine interface of the human pancreas: implications for clinical islet isolation?.  Transplantation. 2006;  81 423-426
  • 13 Uscanga L, Kennedy RH, Stocker S, Grimaud JA, Sarles H. Immunolocalization of collagen types, laminin and fibronectin in the normal human pancreas.  Digestion. 1984;  30 158-164
  • 14 Töns HA, Terpstra OT, Bouwman E. Heterogeneity of human pancreata in perspective of the isolation of the islets of langerhans.  Transplant Proc. 2008;  40 367-369
  • 15 Cross SE, Hughes SJ, Partridge CJ, Clark A, Gray DW, Johnson PR. Collagenase penetrates human pancreatic islets following standard intraductal administration.  Transplantation. 2008;  86 907-911
  • 16 Hilling DE, Rijkelijkhuizen JK, Töns HA, Terpstra OT, Bouwman E. Hyperemic islets, a possible explanation for poor yields in human and porcine islet isolation.  Transplant Proc. 2009;  41 316-318
  • 17 Hanley SC, Paraskevas S, Rosenberg L. Donor and isolation variables predicting human islet isolation success.  Transplantation. 2008;  85 950-955
  • 18 Lakey JR, Warnock GL, Rajotte RV, Suarez-Alamazor ME, Ao Z, Shapiro AM, Kneteman NM. Variables in organ donors that affect the ­recovery of human islets of Langerhans.  Transplantation. 1996;  61 1047-1053
  • 19 Mahler R, Franke FE, Hering BJ, Brandhorst D, Brandhorst H, Brendel MD, Federlin K, Schulz A, Bretzel RG. Evidence for a significant correlation of donor pancreas morphology and the yield of isolated purified human islets.  J Mol Med. 1999;  77 87-89
  • 20 Matsumoto I, Sawada T, Nakano M, Sakai T, Liu B, Ansite JD, Zhang HJ, Kandaswamy R, Sutherland DE, Hering BJ. Improvement in islet yield from obese donors for human islet transplants.  Transplantation. 2004;  78 880-885
  • 21 Nano R, Clissi B, Melzi R, Calori G, Maffi P, Antonioli B, Marzorati S, Aldrighetti L, Freschi M, Grochowiecki T, Socci C, Secchi A, Di Carlo V, Bonifacio E, Bertuzzi F. Islet isolation for allotransplantation: variables associated with successful islet yield and graft function.  Diabetologia. 2005;  48 906-912
  • 22 Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function.  Proc Natl Acad Sci USA. 2006;  103 2334-2339
  • 23 Brissova M, Fowler MJ, Nicholson WE, Chu A, Hirshberg B, Harlan DM, Powers AC. Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy.  J Histochem Cytochem. 2005;  53 1087-1097
  • 24 Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets.  Diabetes. 1988;  37 413-420
  • 25 Stewart ZA, Cameron AM, Singer AL, Dagher NN, Montgomery RA, Segev DL. Histidine-tryptophan-ketoglutarate (HTK) is associated with reduced graft survival in pancreas transplantation.  Am J Transplant. 2009;  9 217-221
  • 26 Basta G, Falorni A, Osticioli L, Brunetti P, Calafiore R. Method for mass retrieval, morphologic, and functional characterization of adult porcine islets of Langerhans: a potential nonhuman pancreatic tissue resource for xenotransplantation in insulin-dependent diabetes mellitus.  J Investig Med. 1995;  43 555-566
  • 27 Coleman R, Silbermann M. Erythrocytes within pancreatic B-cells of corticosteroid-treated mice.  Experientia. 1978;  34 1049-1050
  • 28 Imaoka M, Satoh H, Furuhama K. Age- and sex-related differences in spontaneous hemorrhage and fibrosis of the pancreatic islets in Sprague-Dawley rats.  Toxicol Pathol. 2007;  35 388-394
  • 29 Kaduk B, Husslein EM, Siegfried A. Morphology of the chronic toxicity of busulfan on the islets of Langerhans in the rat.  Hepatogastroenterology. 1987;  34 108-112
  • 30 Lucocq JM, Findlay JA. Islet organ, blood glucose and glucose tolerance of lean and obese Mongolian gerbils. A quantitative study.  Cell Tissue Res. 1981;  220 623-636
  • 31 Moldovan S, Livingston E, Livingston E, Kleinman R, Guth P, Brunicardi FC. Glucose-induced islet hyperemia is mediated by nitric oxide.  Am J Surg. 1996;  171 16-20
  • 32 Henderson JR, Moss MC. A morphometric study of the endocrine and exocrine capillaries of the pancreas.  Q J Exp Physiol. 1985;  70 347-356

Correspondence

D. E. HillingMD 

Leiden University Medical

Center

Department of Surgery, P-01-Q

PO Box 9600

2300 RC Leiden

The Netherlands

Phone: +31/71/526 2857

Fax: +31/71/526 6750

Email: d.e.hilling@lumc.nl

    >