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Cited by 167Pancreatic function and diabetesDiabetes and associated disordersDiabetes Management and Research

Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle

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Christoffersson, Gustaf, Henriksnäs, Johanna, Johansson, Lars, Rolny, Charlotte, Ahlström, Håkan, Caballero-Corbalan, José, Segersvärd, Ralf, Permert, Johan +3 more·2010·Diabetes
DOI 10.2337/db10-0205PMC PMC3279536
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Abstract

OBJECTIVE: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation. RESEARCH DESIGN AND METHODS: The current study presents a new experimental model that is found to be applicable to clinical islet transplantation. Islets were implanted into striated muscle and intraislet vascular density and blood flow were visualized with intravital and confocal microscopy in mice and by magnetic resonance imaging in three autotransplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody, and diabetes was induced by alloxan treatment. RESULTS: Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable with those of islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in autotransplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared with adjacent muscle tissue through high-resolution magnetic resonance imaging. CONCLUSIONS: This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intraislet blood perfusion following transplantation to striated muscle under experimental and clinical situations.

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  • Several alternative transplantation sites to the liver have been proposed in humans, including the subcutaneous space, intramuscular space, and omentum.

    “In humans, several alternative transplantation sites to the liver have been proposed144, including the subcutaneous space145, intramuscular space146, and the omentum147,148.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [146]

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References 46 · Cited by 167

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  1. [1]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 15983207
  2. [2]Mattsson G Jansson L Carlsson PO Decreased vascular density in mouse pancreatic islets after transplantation. Diabetes 2002; 51: 1362– 1366 11978631
  3. [3]Poitout V Briaud I Kelpe C Hagman D Gluco-lipotoxicity of the pancreatic beta cell. Ann Endocrinol (Paris) 2004; 65: 37– 41 15122090
  4. [4]Bennet W Sundberg B Groth CG Brendel MD Brandhorst D Brandhorst H Bretzel RG Elgue G Larsson R Nilsson B Korsgren O Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes 1999; 48: 1907– 1914 10512353
  5. [6]Redmon JB Olson LK Armstrong MB Greene MJ Robertson RP Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J Clin Invest 1996; 98: 2786– 2793 8981925 PMC507744
  6. [7]Shapiro AM Gallant HL Hao EG Lakey JR McCready T Rajotte RV Yatscoff RW Kneteman NM The portal immunosuppressive storm: relevance to islet transplantation? Ther Drug Monit 2005; 27: 35– 37 15665744
  7. [8]Lifson N Kramlinger KG Mayrand RR Lender EJ Blood flow to the rabbit pancreas with special reference to the islets of Langerhans. Gastroenterology 1980; 79: 466– 473 7000613
  8. [9]Lifson N Lassa CV Dixit PK Relation between blood flow and morphology in islet organ of rat pancreas. Am J Physiol 1985; 249: E43– E48 2409813
  9. [10]Samols E Stagner JI Ewart RB Marks V The order of islet microvascular cellular perfusion is B-A-D in the perfused rat pancreas. J Clin Invest 1988; 82: 350– 353 2455737 PMC303515
  10. [11]Stagner JI Samols E The vascular order of islet cellular perfusion in the human pancreas. Diabetes 1992; 41: 93– 97 1345782
  11. [12]Stagner JI Samols E Bonner-Weir S Beta—alpha—delta pancreatic islet cellular perfusion in dogs. Diabetes 1988; 37: 1715– 1721 2903837
  12. [13]Stagner JI Samols E Koerker DJ Goodner CJ Perfusion with anti-insulin gamma globulin indicates a B to A to D cellular perfusion sequence in the pancreas of the rhesus monkey, Macaca mulatta. Pancreas 1992; 7: 26– 29 1372978
  13. [14]Nyman LR Wells KS Head WS McCaughey M Ford E Brissova M Piston DW Powers AC Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 2008; 118: 3790– 3797 18846254 PMC2564611
  14. [15]Bonner-Weir S Orci L New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes 1982; 31: 883– 889 6759221
  15. [16]Lau J Mattsson G Carlsson C Nyqvist D Kohler M Berggren PO Jansson L Carlsson PO Implantation site-dependent dysfunction of transplanted pancreatic islets. Diabetes 2007; 56: 1544– 1550 17400931
  16. [17]Lau J Carlsson PO Low revascularization of human islets when experimentally transplanted into the liver. Transplantation 2009; 87: 322– 325 19202435
  17. [18]Tominaga Y Uchida K Haba T Katayama A Sato T Hibi Y Numano M Tanaka Y Inagaki H Watanabe I Hachisuka T Takagi H More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism. Am J Kidney Dis 2001; 38: S168– S171 11576947
  18. [19]Rafael E Tibell A Ryden M Lundgren T Savendahl L Borgstrom B Arnelo U Isaksson B Nilsson B Korsgren O Permert J Intramuscular autotransplantation of pancreatic islets in a 7-year-old child: a 2-year follow-up. Am J Transplant 2008; 8: 458– 462 18093267
  19. [20]Nahrendorf M Swirski FK Aikawa E Stangenberg L Wurdinger T Figueiredo JL Libby P Weissleder R Pittet MJ The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 2007; 204: 3037– 3047 18025128 PMC2118517
  20. [21]Bryer SC Fantuzzi G Van Rooijen N Koh TJ Urokinase-type plasminogen activator plays essential roles in macrophage chemotaxis and skeletal muscle regeneration. J Immunol 2008; 180: 1179– 1188 18178858
  21. [22]Bohman S Andersson A King A No differences in efficacy between noncultured and cultured islets in reducing hyperglycemia in a nonvascularized islet graft model. Diabetes Technol Ther 2006; 8: 536– 545 17037968
  22. [23]Goto M Eich TM Felldin M Foss A Kallen R Salmela K Tibell A Tufveson G Fujimori K Engkvist M Korsgren O Refinement of the automated method for human islet isolation and presentation of a closed system for in vitro islet culture. Transplantation 2004; 78: 1367– 1375 15548977
  23. [24]Phillipson M Heit B Colarusso P Liu L Ballantyne CM Kubes P Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 2006; 203: 2569– 2575 17116736 PMC2118150
  24. [25]Ahren B Nobin A Schersten B Insulin and C-peptide secretory responses to glucagon in man: studies on the dose-response relationships. Acta Med Scand 1987; 221: 185– 190 3296670
  25. [26]Speier S Nyqvist D Cabrera O Yu J Molano RD Pileggi A Moede T Kohler M Wilbertz J Leibiger B Ricordi C Leibiger IB Caicedo A Berggren PO Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med 2008; 14: 574– 578 18327249 PMC3538807
  26. [27]Nyqvist D Kohler M Wahlstedt H Berggren PO Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes 2005; 54: 2287– 2293 16046293
  27. [28]Menger MD Vajkoczy P Beger C Messmer K Orientation of microvascular blood flow in pancreatic islet isografts. J Clin Invest 1994; 93: 2280– 2285 8182162 PMC294388
  28. [29]Bonner-Weir S O'Brien TD Islets in type 2 diabetes: in honor of Dr. Robert C. Turner. Diabetes 2008; 57: 2899– 2904 18971437 PMC2570382
  29. [30]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 U S A 2006; 103: 2334– 2339 16461897 PMC1413730
  30. [33]Weis J Astrom G Vinnars B Wanders A Ahlstrom H Chemical-shift micro-imaging of subcutaneous lesions. MAGMA 2005; 18: 59– 62 15711849
  31. [34]Markmann JF Rosen M Siegelman ES Soulen MC Deng S Barker CF Naji A Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes 2003; 52: 1591– 1594 12829620
  32. [35]Bhargava R Senior PA Ackerman TE Ryan EA Paty BW Lakey JR Shapiro AM Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 2004; 53: 1311– 1317 15111501
  33. [36]Merani S Toso C Emamaullee J Shapiro AM Optimal implantation site for pancreatic islet transplantation. Br J Surg 2008; 95: 1449– 1461 18991254
  34. [37]Stegall MD Lafferty KJ Kam I Gill RG Evidence of recurrent autoimmunity in human allogeneic islet transplantation. Transplantation 1996; 61: 1272– 1274 8610431
  35. [38]Axen KV Pi-Sunyer FX Long-term reversal of streptozotocin-induced diabetes in rats by intramuscular islet implantation. Transplantation 1981; 31: 439– 441 6454994
  36. [39]Lund T Korsgren O Aursnes IA Scholz H Foss A Sustained reversal of diabetes following islet transplantation to striated musculature in the rat. J Surg Res 2008; 160: 145– 154 19394966
  37. [40]Prior BM Yang HT Terjung RL What makes vessels grow with exercise training? J Appl Physiol 2004; 97: 1119– 1128 15333630
  38. [41]Brown MD Hudlicka O Modulation of physiological angiogenesis in skeletal muscle by mechanical forces: involvement of VEGF and metalloproteinases. Angiogenesis 2003; 6: 1– 14 14517399
  39. [42]Nozawa H Chiu C Hanahan D Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A 2006; 103: 12493– 12498 16891410 PMC1531646
  40. [43]Girn HR Ahilathirunayagam S Mavor AI Homer-Vanniasinkam S Reperfusion syndrome: cellular mechanisms of microvascular dysfunction and potential therapeutic strategies. Vasc Endovascular Surg 2007; 41: 277– 293 17704330
  41. [44]Weber C Fraemohs L Dejana E The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 2007; 7: 467– 477 17525755
  42. [45]Olerud J Johansson M Lawler J Welsh N Carlsson PO Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets. Diabetes 2008; 57: 1870– 1877 18420490 PMC2453615
  43. [46]Geissmann F Jung S Littman DR Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003; 19: 71– 82 12871640

Authors
Christoffersson, G., Henriksnäs, J., Johansson, L., Rolny, C., Ahlström, H., Caballero-Corbalan, J., Segersvärd, R., Permert, J., Korsgren, O., Carlsson, P.-O., & Phillipson, M.
Affiliations
  • Uppsala University (SE)
  • Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden;
  • Karolinska Institutet (SE)
Corresponding author
Phillipson, Mia
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2010-07-22
Volume
59
Issue
10
Pages
2569-2578
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db10-0205
PMC
PMC3279536
OpenAlex
W2103706790
Cited by
167
References
46
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 13 · 2022: 3 · 2021: 9 · 2020: 7 · 2019: 16 · 2018: 9 · 2017: 16 · 2016: 12 · 2015: 16 · 2014: 4 · 2013: 19 · 2012: 9
FWCI
16.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Royal Swedish Academy of Sciences
  • University of New South Wales
  • Svenska Sällskapet för Medicinsk Forskning
  • Stiftelsen Familjen Ernfors Fond
  • Uppsala Universitet
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
islet transplantation, striated muscle, islet revascularization, type 1 diabetes, neutrophils, autologous transplantation, alloxan-induced diabetes, forearm muscles
MeSH terms
Adenosine Diphosphate, Adenosine Triphosphate, Animals, Blood Glucose, Cell Separation, Diabetes Mellitus, Experimental, Islets of Langerhans, Leukocytes, Male, Mice, Inbred C57BL, Mice, Nude, Neutrophils, Organ Culture Techniques, Reoperation, Transplantation, Autologous, Transplantation, Heterotopic, Islets of Langerhans Transplantation, Muscle, Skeletal, Leukocyte Reduction Procedures, Mice

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