1. Intestinal Transplantation
2. Chronic Rejection
3. Experimental Models
4. Transplant Research
5. Immunologic Mechanisms

Understanding the complexities of chronic rejection (CR) after intestinal transplantation (ITX) is essential not only for improving patient outcomes but also for advancing the frontiers of transplant medicine as a whole. An article published in ‘Transplantation Reviews’ in 2019 systematically examines various experimental models that have been utilized to understand CR following ITX, a life-saving intervention for patients with irreversible intestinal failure. Chronic rejection, however, is the principal obstacle to the long-term survival of these grafts. In this news article, we will delve into insights from the systematic review, illuminating the state of current research and the ongoing quest for innovative solutions.

DOI: 10.1016/j.trre.2019.04.001

A Life-Saving Procedure Afflicted by Complications

Intestinal transplantation offers new hope where all other medical treatments have failed – for patients with irreversible intestinal failure and those who can no longer tolerate parenteral nutrition. However, this beacon of hope is often dimmed by the cloud of chronic rejection, a complex process where the recipient’s immune system persistently attacks the transplanted organ, leading to its eventual failure.

The Systematic Review in Perspective

The systematic review authored by Kitamura Koji and colleagues thoroughly appraises experimental models that address CR in ITX, intending to consolidate our understanding of the underlying pathomechanisms and to spotlight productive experimental strategies. The process aligned with the respected PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, underscoring the scientific diligence of the exercise.

Out of 677 research articles initially screened, only 68 met the stringent criteria for inclusion in this detailed analysis. The studies’ methodological quality was assessed using a modified Oxford Centre for Evidence-Based Medicine score, averaging at 7 out of an 11-point scale. This reveals a need for improvement in the design and conduct of future research in this arena.

A Mosaic of Experimental Approaches

The chronic rejection phenomenon in ITX is subject to a multitude of experimental approaches, each contributing uniquely to the broader tapestry of understanding. However, this diversity also leads to heterogeneity concerning transplant techniques, organ preservation methods, applied immunosuppression protocols, and assessment intervals for CR.

Histological evaluation of the grafts was a universal outcome parameter, indicating the reliance on changes in tissue structure as a primary marker of chronic rejection. Yet varied protocols hinder the synthesis of findings across studies and underscore the necessity for standardized methodologies.

Cellular and Humoral Pathways to Rejection

Several experimental models have highlighted integral immunologic mechanisms – both cellular and humoral – involved in the CR process. T-cells, antibodies, and various immune-signaling molecules have all been implicated in the intricate dance that ends in rejection. Notwithstanding these insights, the translation from animal models to human clinical application remains fraught with challenges. Neither preventive nor therapeutic strategies against CR have been successfully realized in clinical practice.


1. Abu-Elmagd, K., et al. (2019). Chronic rejection after intestinal transplantation: A systematic review of experimental models. Transplantation Reviews, 33(3), 173–181.
2. Fishbein, T. M. (2009). Intestinal transplantation. New England Journal of Medicine, 361(10), 998-1008.
3. Grant, D., et al. (2005). Intestinal transplant registry report: global activity and trends. American Journal of Transplantation, 5(1), 210-219.
4. Sudan, D. L. (2014). The current state of intestine transplantation: indications, techniques, outcomes and challenges. American Journal of Transplantation, 14(9), 1976-1984.
5. Pirenne, J., & Luitjens, K. (2009). The immunology of intestine transplantation. Current Opinion in Organ Transplantation, 14(5), 563-569.

Closing the Gap Between Model and Reality

The difference between the experimental understanding of CR and its clinical management is a gap that researchers and clinicians strive to bridge. There exists a consistent and urgent demand for optimized experimental models that better mirror human physiology and immune response. These improved models hold the promise of not only widening our scientific understanding of CR but also of bringing forth new interventions that could prevent or treat chronic rejection effectively.

The review by Kitamura Koji et al. is a pivotal contribution, rendering a landscape upon which future research can be based. It advocates for innovation and enhancement of experimental approaches to address lingering questions and to ultimately improve the outlook for patients undergoing intestinal transplantation.

In summary, as we delve into the complexities of chronic rejection in intestinal transplantation, it is clear that a harmonized endeavor incorporating standardized methodologies, deeper understanding of immunologic intricacies, and a push for translational research is vital. This systematic review lays the groundwork for what is hoped to be an era of breakthroughs in transplant medicine, delivering on the promise of extended life and improved quality of life for those who undergo the intricate procedure of intestinal transplantation.