Islets Transplantation

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Continuing Education Activity

Pancreatic islet cell transplantation is performed to prevent unrecognized hypoglycemia in type I diabetics. The procedure involves placing Islet cells into the portal vein via ultrasound or fluoroscopic guidance; laparoscopic placement has also been described. Indications for Islet cell transplantation include type I diabetics who have attempted to control their hypoglycemic episodes medically but continue to have hypoglycemic episodes without recognizing them. This activity reviews the evaluation and selection of patients suitable for pancreatic islet cell transplantation while also highlighting the role of the inter-professional team in evaluating and treating this condition.


  • Identify the anatomical structures of the pancreas on both the gross anatomic and histologic levels.
  • Review the current and possible future indications for islet cell transplantation.
  • Outline the steps/techniques and identify the equipment used in performing islet cell transplantation.
  • Summarize potential complications in patients receiving islet cell transplantation and review the clinical significance of these complications.


Pancreatic islet cell transplantation can reduce the number of unrecognized, hypoglycemic episodes refractory to medical management. The procedure has also had success in helping patients achieve independence from exogenous insulin administration. This procedure is less invasive than a solid organ pancreas transplant and is considered one of the safest transplant procedures with the potential to cure type I diabetes. Current research focuses heavily on promoting cell survival after transplantation. Inhibitory receptors within islet cells have shown to promote both function and survival under inflammatory and hyperglycemic stress states following graft transplantation.[1][2]

Anatomy and Physiology

The pancreas is made up of three parts: a head, body, and tail. The head receives its blood supply from the superior and inferior pancreaticoduodenal arteries, while branches from the splenic artery supply the body and tail. It has both exocrine and endocrine functions. A network of open circulation exists between the exocrine and endocrine pancreas physically linking the two via an integrated vascular system.

Islet cells are clusters of cells that are found throughout the pancreas and are responsible for its endocrine function. Islet cells are made up of five different types of cells, each secreting a unique hormone. Alpha cells secrete glucagon, delta somatostatin, beta insulin, gamma pancreatic polypeptide, and epsilon ghrelin. These hormones are secreted directly into the bloodstream in response to various stimuli.[3][4][5][6]


Islet cell transplantation is currently approved for patients with type I diabetes mellitus who experience unrecognized hypoglycemic episodes that are refractory to medical management. Long term follow-up has shown as many as 50 to 70% of patients remain insulin independent five years after transplant. These results show promising potential for allograft islet cell transplantation use for the treatment of type I diabetes mellitus. One of the major deterrents to this procedure gaining acceptance as a definitive cure is the requirement of lifelong immunosuppressants to prevent graft loss. Promising research in mice has shown improved graft survival with inhibition of a Prostaglandin D2 receptor. This receptor, GPR44/DP2, results in impaired insulin secretion once activated. 

Inclusion criteria:

  • Mentally stability and able to adhere to protocols
  • History consistent with type I diabetes, age of onset <40 years, insulin-dependent for >5 years
  • Age range 18 to 65
  • Despite adherence to intense insulin regimen and expert direction, the patient has at least two documented episodes of symptomatic hypoglycemia within a six month time interval.[2][7]


Donor pancreatic islet cells are infused into the recipient via the portal system. A portal venous pressure above 20 mmHg at baseline is a contraindication to transplantation due to the significantly increased risk of thrombosis. After a patient receives an islet cell allograft, they require lifelong immunosuppression. Because of this requirement, an inability to tolerate immunosuppression is a contraindication to transplantation.

Grafts also do not survive well when the body is fighting an active infection making active infection another contraindication. Malignancy is another contraindication, except for patients that have been cancer-free for more than five years after the excision of cutaneous basal cell or squamous cell carcinoma.[8][9]


There are varying techniques involving variations in types of equipment used for islet cell transplantation. The equipment listed will be for the procedure that is the current standard and was first described in 1987 by Ricordi. 

  • Two 16-20 gauge angiocatheters 
  • collagenase and a serine-protease inhibitor
  • Ricordi chamber (chamber separated by a filter with pores)
  • Nine stainless steel balls
  • peristaltic pump
  • Hank's solution
  • Heating circuit
  • Dithizone stain
  • Coils and gelatin sponges
  • Interventional radiologic imaging modality (ultrasound, fluoroscopy) [10]


This procedure is rapidly evolving as technology changes. Due to the radiologic equipment, the procedure routinely uses radiologists and radiologic personnel during the infusion of the cells. Transplant surgeons historically drove islet cell therapy, but now interventional radiologists are positioned in an important role for both clinical performance and research. Interventional radiologists and their team can share some of the roles and responsibilities of transplant surgeons and their technologists. Personnel typically required to perform the procedure may include, but are not limited to:

  • Transplant surgeon
  • Surgical technologist
  • Radiologist
  • anesthesiologist/C.R.N.A
  • Nurse [11]


Patients that may benefit from the procedure are first assessed and identified by endocrinologists. Patients that meet the criteria are then evaluated by a psychologist to determine their motivation and ability to commit to therapy. Transplant surgeons harvest the islet cells from deceased donors.

After harvesting islet cells, they must be separated from the exocrine pancreas in an enzymatic and density centrifugation process. Grafts then undergo assessment and rate as adequate when they contain 5,000 high-quality islets per Kg (recipient). Typically recipients are infused with islet cells from multiple donors. Infusing a larger number of islets increases the chances that an adequate number will survive.[12] 


Islets are isolated from the donor, but first, the duodenum and spleen are detached from the pancreas as well as lymph nodes, vessels, and peri-pancreatic fat. The head of the pancreas is then transected, and the catheters are placed into the main pancreatic duct. The pancreas is then perfused with the collagenase solution. The pancreas undergoes 10 minutes of cold perfusion and is then sliced into smaller pieces before being placed into the inferior portion of the Ricordi chamber. The digestive, enzymatic solution is then infused into the chamber. Hank's solution is subsequently released as a pump cycles the mixture.

The temperature is manipulated, and the solution circulated until islets are cleared from acinar tissue. The islets are collected and then stained with dithizone to evaluate them. Once the purity, viability, potency, and stability are verified through digital computer analysis, the islets are ready for the infusion process. Islet cells have a stability time of 72 hours after the harvesting process. They must be infused within 72 hours of harvesting to promote the best chance at survival. 

The donor islets must not exceed a tissue volume of 5 ml, which are then diluted with heparin and 40 to 60 ml of a solution, such as lactated Ringer. Graft implantation can be in multiple ways. Mini laparotomy with cannulation of one of the mesenteric or omental veins is one method performed by transplant surgeons. Another technique that is typically performed by interventional radiologists is accessing the portal vein under image guidance. It takes approximately 15 minutes to infuse the bag of islets, heparin, and solution once a vein has been cannulated. The portal vein pressure is monitored and must be kept at or below 22 mmHg. Once the infusion is complete and the catheter is removed from the vein, the gelatin sponges and coils are placed into the cannulation site.[10]


As with any surgical procedure, there can be possible complications. One of the most common complications is portal vein thrombosis. Thrombosis can lead to complete loss of the graft; however, since the addition of heparin in the infusion process, life-threatening thrombosis is rare.

Bleeding is another among the most frequent complications, occurring in up to 8% of islet transplant procedures. Mycotic aneurysms, infections, pancreatic fistulas, bile leak, and pancreatitis are some of the other complications that may occur with islet cell transplantation. As many as 30% of patients that undergo the procedure will need a repeat operation.[13]

Clinical Significance

In the clinical setting, the majority of grafts fail in the immediate post-infusion period; this is due to an extreme inflammatory response that occurs called the instant blood mediated inflammatory reaction. In this process, tissue factor on islet cells attracts and activates platelets resulting in a cascade of additional immune cell recruitment and clot formation. Anticoagulants and intense anti-inflammatory agents aim to minimize this process and subsequently prevent immediate rejection.

One of the main goals of islet cell transplantation is that patients will be able to achieve some form of insulin independence. The rate of insulin independence varies widely among centers, 20 to 90%. Long-standing experience with the infusion process appears to be the most influential factor in regards to the center's success rate. Insulin independence from islet cell infusion has an expiration date. Results are not lifelong and require another round of infusions after approximately three years to maintain independence. Beta cells can retain some function up to 5 years after infusion. 

Islet cell transplantation is now in use in the clinical setting; however, the harvesting, curating, and infusion process continues to evolve as ongoing discoveries occur in the experimental setting. This process will continue, which will produce more consistent and sustainable results in the clinical setting.[14][15]

Enhancing Healthcare Team Outcomes

The coordination and management of all physicians, nurses, technicians, and office staff needed for a single patient to undergo pancreatic islet cell transplantation requires clear communication between various teams and strict protocol adherence. Endocrinologists initiate the first step with the identification of potential patients. They must clearly communicate the patient's medical history, failed attempts at medical management, and recurrent episodes of unrecognized hypoglycemia to the transplant surgeon. The endocrinologist must also disclose the patient's history to a psychologist. Details of the patient's course become essential for a psychologist for them to understand and assess the patient's motivation to undergo the procedure. 

Communication, coordination, and standardization of how the islets are transplanted are of paramount importance. An Australian trial demonstrated that standardization of islet isolation allowed for results of trials performed at different sites to be comparable. Diminishing these procedural variations, which could be affecting outcomes, will enable further discovery as to what promotes graft survival. Improving graft survival will decrease patient morbidity as well as the need for repeat transplantation and additional medications. [Level 2]

Posttransplantation, patients require lifelong immunosuppression. A team of pharmacists, physicians, and psychologists are needed to ensure the medications chosen are tailored to the patient. Patients will continue to need blood glucose checks and regular appointments with different teams. Interprofessional communication amongst the various groups is essential to ensure regimen adherence, identify barriers to adherence, monitoring for side effects (mental and physical), and checking for graft functionality over time.[16] [Level 3] 

Article Details

Article Author

Kevin T. Spence

Article Editor:

Danielle E. Ladie


8/8/2022 8:57:59 PM

PubMed Link:

Islets Transplantation



Dinnyes A,Schnur A,Muenthaisong S,Bartenstein P,Burcez CT,Burton N,Cyran C,Gianello P,Kemter E,Nemeth G,Nicotra F,Prepost E,Qiu Y,Russo L,Wirth A,Wolf E,Ziegler S,Kobolak J, Integration of nano- and biotechnology for beta-cell and islet transplantation in type-1 diabetes treatment. Cell proliferation. 2020 Apr 27;     [PubMed PMID: 32339373]


Abadpour S,Tyrberg B,Schive SW,Huldt CW,Gennemark P,Ryberg E,Rydén-Bergsten T,Smith DM,Korsgren O,Skrtic S,Scholz H,Winzell MS, Inhibition of the prostaglandin D{sub}2{/sub}-GPR44/DP2 axis improves human islet survival and function. Diabetologia. 2020 Apr 29;     [PubMed PMID: 32350565]


Dybala MP,Kuznetsov A,Motobu M,Hendren-Santiago BK,Philipson LH,Chervonsky AV,Hara M, Integrated Pancreatic Blood Flow: Bi-Directional Microcirculation Between Endocrine and Exocrine Pancreas. Diabetes. 2020 Mar 20;     [PubMed PMID: 32198213]


Panzer JK,Hiller H,Cohrs CM,Almaça J,Enos SJ,Beery M,Cechin S,Drotar DM,Weitz JR,Santini J,Huber MK,Muhammad Fahd Qadir M,Pastori RL,Domínguez-Bendala J,Phelps EA,Atkinson MA,Pugliese A,Caicedo A,Kusmartseva I,Speier S, Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis. JCI insight. 2020 Apr 23;     [PubMed PMID: 32324170]


Zhao L,Wang L,Aierken R,Wang W,Wang X,Li M, Characterization of Insulin and Glucagon Genes and Their Producing Endocrine Cells From Pygmy Sperm Whale ({i}Kogia breviceps{/i}). Frontiers in endocrinology. 2020;     [PubMed PMID: 32296396]


Villarreal D,Pradhan G,Wu CS,Allred CD,Guo S,Sun Y, A Simple High Efficiency Protocol for Pancreatic Islet Isolation from Mice. Journal of visualized experiments : JoVE. 2019 Aug 30;     [PubMed PMID: 31524856]


Shapiro AM,Pokrywczynska M,Ricordi C, Clinical pancreatic islet transplantation. Nature reviews. Endocrinology. 2017 May;     [PubMed PMID: 27834384]


Venturini M,Sallemi C,Marra P,Palmisano A,Agostini G,Lanza C,Balzano G,Falconi M,Secchi A,Fiorina P,Piemonti L,Maffi P,Esposito A,De Cobelli F,Del Maschio A, Allo- and auto-percutaneous intra-portal pancreatic islet transplantation (PIPIT) for diabetes cure and prevention: the role of imaging and interventional radiology. Gland surgery. 2018 Apr;     [PubMed PMID: 29770308]


Flatt AJS,Bennett D,Counter C,Brown AL,White SA,Shaw JAM, β-Cell and renal transplantation options for diabetes. Diabetic medicine : a journal of the British Diabetic Association. 2020 Apr;     [PubMed PMID: 31705689]


Piemonti L, Islet Transplantation 2000;     [PubMed PMID: 25905200]


Gaba RC,Garcia-Roca R,Oberholzer J, Pancreatic islet cell transplantation: an update for interventional radiologists. Journal of vascular and interventional radiology : JVIR. 2012 May;     [PubMed PMID: 22417970]


McCall M,Shapiro AM, Update on islet transplantation. Cold Spring Harbor perspectives in medicine. 2012 Jul;     [PubMed PMID: 22762022]


Wojtusciszyn A,Branchereau J,Esposito L,Badet L,Buron F,Chetboun M,Kessler L,Morelon E,Berney T,Pattou F,Benhamou PY,Vantyghem MC, Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d'endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie - dialyse - transplantation (SFNDT). Diabetes     [PubMed PMID: 30223084]


Srinivasan P,Huang GC,Amiel SA,Heaton ND, Islet cell transplantation. Postgraduate medical journal. 2007 Apr     [PubMed PMID: 17403947]


Gamble A,Pepper AR,Bruni A,Shapiro AMJ, The journey of islet cell transplantation and future development. Islets. 2018 Mar 4     [PubMed PMID: 29394145]


Schuetz C,Markmann JF, Islet cell transplant: Update on current clinical trials. Current transplantation reports. 2016 Sep;     [PubMed PMID: 28451515]