Immunobiology of Transplantation: Impact on Targets for Large and Small Molecules

Abstract

Organ transplantation is the preferred method of treatment for many forms of end-stage organ failure. However, immunosuppressive drugs that are used to avoid rejection can result in numerous undesirable effects (infection, malignancy, hypertension, diabetes, and accelerated arteriosclerosis). Moreover, they are not effective at preventing chronic rejection resulting in late graft loss. This review summarizes the fundamental concepts underlying the rejection of solid-organ allografts with the aim of highlighting potential new targets for therapeutics. Future improvement will depend on new therapeutic moieties, including biologics, to target various pathways of both the innate and adaptive arms of immunity. Results from some of the most recent clinical trials in transplantation and emerging new therapies are also discussed.

Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization

“…The cervix was gently lifted up to expose the intact uterine artery and veins, which also enabled the attachment of a titanium clip (Weck Closure Systems Ltd, Resarch Triangle Park, NC, USA) on the superior gluteal vessels. The common iliac vessels and the lumbar vessels (2)(3)(4) were then transected between double ligatures. Both uterine horns were then double ligated and cut at a site between the tip of the uterine horn and the oviduct.…”

“…Although, human allogeneic UTx may prove to be successful in terms of pregnancy, there will still be problems related to the surgical risk to retrieve the uterus from a live donor and the adverse effects that are related to the intake of immunosuppression [4]. Recent progress in stem cell research and biomaterials has given hope to the replacement of a live donor as an organ source, with a customized organ construct for transplantation using autologous cells [5], thus circumventing main obstacles in organ transplantation such as lack of donor organs and long-term immunosuppressive treatments.…”

Heme Oxygenase, Inflammation, and Fibrosis: The Good, the Bad, and the Ugly?

“…A major problem in transplantation biology is the immunological barrier between donor and recipient, which may cause graft rejection. Based on clinical and pathological criteria, graft rejection has been classified into three major forms: hyperacute, acute, and chronic graft rejection (Azimzadeh et al, 2011). Hyperacute rejection starts within minutes of transplantation and exhibits thrombosis of graft vessels and ischemic necrosis due to circulating recipient antibodies, and organ failure occurs hours after transplantation.…”

Uterine Tissue Engineering and the Future of Uterus Transplantation

“…All transplanted patients face the risks of tissue rejection and immunosuppressant-related side effects 85. Long-term graft survival remains a challenge5,9 and patients become susceptible to infections and certain malignancies, including increased risks of hypertension, diabetes and accelerated arteriosclerosis 5. High doses of immunosuppressive drugs following UTx may, at least temporary, be required to halt progression of organ rejection.…”