Update on islet cell transplantation for type 1 diabetes

Abstract

Despite modern medical breakthroughs, diabetes mellitus is a worldwide leading cause of morbidity and mortality. Definitive surgical treatment of diabetes mellitus was established with the advent and refinement of clinical pancreas transplantation in the 1960s. During the following decades, critical discoveries involving islet isolation and engraftment took place. Clinical islet cell transplantation represents the potential for reduced insulin requirements and debilitating hypoglycemic episodes without the morbidity of surgery. Unfortunately, islet cell transplantation was unable to achieve comparable results with solid organ transplantation. This was until the Edmonton protocol (steroid-free immunosuppression) was described, which demonstrated that islet cell transplantation could be a viable alternative to pancreas transplantation. Significant advances in islet purification techniques and novel immunomodulatory agents have since renewed interest in islet cell transplantation. Yet the field is still challenged by a limited supply of islet cells, inadequate engraftment, and the deleterious effects of chronic immunosuppression. This article discusses the history and the current status of clinical islet cell transplantation.

Keywords: Islet cell transplantation; Type 1 diabetes; β cells.

Figure 1

Technique for percutaneous transhepatic pancreatic Islet cell transplantation. (A–C) Three sequential images of a digitally subtracted portogram using a 21-gauge percutaneously placed micropuncture needle (arrow at needle tip access of a small peripheral portal vein radical) via a right intercostal approach. This is typical of the fluoroscopic-guided right-sided percutaneous transhepatic approach. The dashed circle (B) is the site of the definitive access and correlates with the dashed circle in (D). (D) Single fluoroscopic spot image of the 21-gauge micropuncture access needle (arrow at the definitive needle tip access of a small peripheral portal vein radical) via a right intercostal approach. The dashed circle is the site of the definitive access and correlates with the dashed ellipse in (B). (E–F) Two sequential images of a digitally subtracted access portogram and initial access with a 5F micropuncture transition sheath catheter (solid arrow at catheter tip in right portal vein). The 5F transition sheath enables the operator to upsize the 0.018-inch wire for a 0.035-inch wire. The dashed arrows in (F) indicate some of the right-sided peripheral portal radicals. LPV, left portal vein; MPV, main portal vein; RPV, right portal vein. (G) Single digitally subtracted angiogram of the formal percutaneous transhepatic portogram just before the infusion of the pancreatic islets. The transhepatic portogram is being performed using a 5F pigtail catheter with its formed pigtail tip (solid black arrow) in the proximal portal vein near the confluence of the splenic vein and the mesenteric vein(s). The 5F pigtail catheter has been advanced through a short (11-cm) 6F transhepatic sheath (solid white arrow at sheath tip), which is placed to secure the percutaneous transhepatic access. At this point in time, the operator measures pressures through the pigtail catheter to obtain a baseline portal pressure. In this case the portal pressure was 9 mm Hg. Most operators use a cutoff of 10 to 12 mm Hg to decide whether to proceed with the islet cell infusion (<10 to 12 mm Hg is acceptable for subsequent islet cell infusion). The infusion of islets occurs over 15 to 40 minutes, depending on the volume of tissue to be infused and the changes in portal pressure that occur during islet infusion. The portal pressures are measured every 5 minutes interrupting the infusion. If the portal pressure doubles, the infusion is held until the pressure returns toward baseline. RPV, right portal vein; LPV, left portal vein. (H) Photograph of the pancreatic islet cell infusion. The islets are gradually infused by gravity using a closed bag system (hollow arrow). The infusion catheter in the portal vein is a 4- to 5F endhole catheter. (I) Single digitally subtracted angiogram of the percutaneous transhepatic portogram just after the pancreatic islet cell infusion. The transhepatic portogram is again being performed using the 5F pigtail catheter with its formed pigtail tip (solid black arrow) in the proximal portal vein. The formal postinfusion portogram is performed to rule out portal vein thrombosis, which can occur with pancreatic islet cell transplantation via the portal vein. At this time, the portal pressure is measured through the pigtail catheter to obtain a postprocedural portal pressure. In this case the portal pressure was 17 mm Hg. LPV, left portal vein; MPV, main portal vein; RPV, right portal vein. (J) Single fluoroscopic spot image of the transhepatic track near the portal vein radical that had been accessed. The peripheral portal vein radicals are seen filled with contrast (dashed arrows). Contrast is being injected through the 6F sheath (open arrow at radio-opaque sheath tip). The transhepatic track is seen between the two solid black arrows. (K) Single fluoroscopic spot image of the transhepatic track (between the solid black arrows) after the contrast has been washed away by the portal flow. Only the contrast in the transhepatic track (between solid arrows) is now seen. The open arrow points to the radio-opaque sheath tip. (L–N) Three fluoroscopic spot images in sequence as contrast-impregnated Gelfoam torpedoes are deployed in the transhepatic track to achieve hemostasis. (L) Deployment of the first (deeper) Gelfoam torpedo (boxed arrow 1). Notice that the actual sheath tip (open arrow) is beyond the radio-opaque marker of the sheath. (M) After the deployment of the first and second Gelfoam torpedoes (boxed arrows 1 and 2, respectively). The third Gelfoam torpedo (between solid arrows) is being deployed and is just within the actual tip of the sheath (open arrow). (N) After the deployment of all three contrast-impregnated Gelfoam torpedoes (boxed arrows 1 to 3), the actual sheath tip has fallen out of the capsular orifice of the transhepatic track.