Experimental immuno‐alteration

Abstract

In the past few years, remarkable advances have been made in preventing rejection of islet ailografts and xenografts (rat to mouse) by 6 procedures which do not involve continuous immunosuppressive therapy of recipient rodents. Four methods alter or destroy passenger lymphoid cdls in the islets prior to transplantation. These include in vitro culture of donor rat islets at low temperature and a single injection of anti-lymphocyte serum in the recipients, culture of rat or mouse islet aggregates in 95% 02, and pretreatment of mouse islets with Ia antibody and complement or with a monoclonal antidendritic cell antibody and complement. Two methods induce partial tolerance in recipients by preimmunization with donor blood treated either with Ia antibody and complement or ultraviolet irradiation. These preimmunization procedures permit the use of untreated donor islets.Two methods have been developed for the mass isolation of canine islets. Initial studies indicate that low-temperature culture of donor canine islets and a single injection of anti-lymphocyte serum will prevent rejection of canine islet allografts. The technical problems remaining for human islet allografts are selection of the optimum method of preventing islet allograft rejection based on studies in the dog, adaptation of the mass islet isolation techniques to the human pancreas, and selection of a safe and optimum site for transplantation.

Chondrocytes within Osteochondral Grafts Are More Resistant than Osteoblasts to Tissue Culture at 37°C

“…In conclusion, a simple procedure such as the incubation of osteochondral allografts at 37 • C for [16][17][18][19][20][21][22][23][24] hr prior to the currently applied storage conditions at 4 • C [18] might result in the development of an optimized osteochondral allograft with intact cartilage but devitalized bone [12]. Furthermore, recent evidence strongly suggests that the storage at 37 • C can be extended for several weeks without any adverse effect on the cartilage [32].…”

“…Whereas at 4 • C the metabolic activity of the cells is reduced and might thus limit the extent of the bone cell's starvation, at 37 • C their incapability to cope with the mode of nutritional supply may unfold under tissue culture conditions. More than 30 years ago, the concept of adding a tissue culture phase at room temperature or at 37 • C prior to transplantation-with the aim of prolonging allograft survival, e.g., of skin, thyroids, and Langerhans islets-was introduced [19][20][21][22][23]. The idea behind this was to remove immunologically active cells within the transplanted tissues [24].…”

Interaction of Cooling Rate, Warming Rate, and Extent of Permeation of Cryoprotectant in Determining Survival of Isolated Rat Islets of Langerhans During Cryopreservation

“…Three principal approaches have been proposed for minimizing the need for strong immunosuppression: the first is to obtain the best possible match between donor and recipient, the second is to make the recipient tolerant of the donor tissue, and the third involves a variety of procedures aimed at reducing the immunogenicity of the donor tissue (3)(4)(5). In each case, cryogenic preservation of the donor islets offers several important benefits (6).…”

Canine Islets in an Ultrafiltered Environment

“…The addition of tissue is superior to insulin administration in a very special way with respect to preventing and to some degree reversing the microvascular lesions of diabetes (43). However, clinical application has been disappointing ( 6 ) , and alternative approaches to the delivery or immune manipulation of islet tissue are necessary (7). Immunosuppression is not a desirable adjunct to long-term endocrine replacement, and immune alteration of islet tissue remains to a large degree theoretical (6).…”