Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplantation in rats

Abstract

Islets of Langerhans have been enclosed in polycarbonate diffusion chambers and transplanted intraperitoneally to syngeneic streptozotocin diabetic rats. Direct implantation of 1100--1400 islets in these chambers failed to reverse diabetes during a period of 12 weeks, and viable islet tissue was not recoverable at the end of this period. Islets placed in chambers which had been implanted 3--12 weeks previously similarly failed to lower blood glucose of diabetic recipients, as a result of lack of survival of the islets. Insulin infusion into chambers previously implanted in vivo, I125 insulin diffusion studies in chambers recovered 6--8 weeks after implantation, and scanning electron microscopy of the recovered membranes all indicated that the pores were not totally occluded. The failure of islet transplantation via chambers in this simple syngeneic model has discouraging implications for their use as a means of avoiding allograft rejection.

Chronic response of adult rat brain tissue to implants anchored to the skull

“…The ensheathing reaction is believed to be a major contributing factor to decreases in indwelling device performance; however, the precise mechanisms that cause failure are not known [13][14][15][16][17][18][19][20][21][22][23]. For example, catheters implanted for draining excessive cerebrospinal fluid can be blocked by cellular ingrowth and may require frequent surgical revision [22,23].…”

“…For example, catheters implanted for draining excessive cerebrospinal fluid can be blocked by cellular ingrowth and may require frequent surgical revision [22,23]. Increases in microelectrode impedance and loss of neuronal recording has been attributed to the encapsulating brain tissue response [13,20,21], and it has been suggested that glial encapsulation may reduce the permeability of microdialysis membranes and cell encapsulation devices [17][18][19]24].…”

In vivo Studies on Insulin Permeability of an Immunoisolation Device Intended for Islet Transplantation Using the Microdialysis Technique

“…At this time, the amount of insulin recovered and the kinetics have almost fully returned to normal and are not significantly different from those in the control group. This is a rather unexpected finding, since several publications report increasing fibrosis during the first months after implantation [19][20][21][22]. A possible explanation could be changes in, or even degradation of, the membrane material.…”

“…The in vivo diffusion barrier will depend partly on the immunoisolating membrane but also on the tissue reaction in the recipient. The development of an avascular foreing body reaction around an implant, a common problem in the fields of both macro-and microencapsulation, will hinder the survival and function of the encapsulated graft, while a well-vascularized surrounding tissue should be favorable [19][20][21][22].…”

Pancreas and islet transplantation

“…Theoretically a semiporous membrane will exclude cells or molecules able to mediate rejection, while allowing flux of insulin and glucose. The composition, structure and diffusion characteristics of several membranes and chambers and the problems with their use has been assessed by Theodorou et al [239].…”