Research of Small-Molecule Therapeutics in Transplantation and Tolerance

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 1323

Special Issue Editor


E-Mail Website
Guest Editor
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Interests: molecular biochemistry; cell biology; immunology; small molecule pharmacokinetics

Special Issue Information

Dear Colleagues,

Organ transplantation is the best curative treatment for patients with end-stage organ disease. An unavoidable complication leading to early allograft dysfunction is mediated primarily by ischemia-reperfusion injury (IRI). This peri-transplant clinical condition is characterized by interrelated phases involving donor-tissue ischemic necrosis and recipient reperfusion, which introduces the innate-adaptive immune interface that promotes pro- and anti-inflammatory responses. As the consequences of I/R injury remain vast, understanding the mechanistic factors leading to I/R injury remains a top priority. Determining the peak induction potential of the signaling networks that attenuate antioxidant, detoxification, and homeostatic functions may be the key to understanding why specific therapeutic strategies fail to advance through clinical trials.

In the past year, small-molecule therapeutics, comprised of RNA, protein, and/or drug-based molecules, have achieved impressive results regulating gene expression networks involved in pro- and anti-inflammatory responses to organ transplantation injury. They have been shown to significantly increase the capacity to prevent organ rejection by reducing oxidative stress and inflammation, modulating the immune response, and stimulating the production of protective enzymes that promote tissue repair. The aim of this Special Issue is to illustrate how these small molecules hold the potential to improve the survival of patients undergoing solid organ transplantation.

Dr. Kenneth J. Dery
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • organ transplantation
  • oxidative stress
  • ischemia-reperfusion injury
  • short-activating RNA
  • small-molecule therapeutics
  • early allograft dysfunction
  • morpholinos

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

11 pages, 816 KiB  
Article
Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study
by Massimiliano Veroux, Floriana Sanfilippo, Giuseppe Roscitano, Martina Giambra, Alessia Giaquinta, Giordana Riccioli, Domenico Zerbo, Daniela Corona, Massimiliano Sorbello and Pierfrancesco Veroux
Biomedicines 2024, 12(2), 290; https://doi.org/10.3390/biomedicines12020290 - 26 Jan 2024
Viewed by 820
Abstract
Background: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing [...] Read more.
Background: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). Results: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor’s age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40–3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50–4.51, p < 0.001), the donor’s acute kidney injury (OR 2.71, 95% CI: 1.61–4.52, p = 0.021) and, above all, the recipient’s arterial hypotension (OR 5.06, 95% CI: 2.52–10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival. Full article
Show Figures

Graphical abstract

Review

Jump to: Research

22 pages, 2385 KiB  
Review
Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting
by Dario Troise, Barbara Infante, Silvia Mercuri, Valeria Catalano, Elena Ranieri and Giovanni Stallone
Biomedicines 2024, 12(6), 1240; https://doi.org/10.3390/biomedicines12061240 - 3 Jun 2024
Viewed by 213
Abstract
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a [...] Read more.
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies. Full article
Show Figures

Figure 1

Back to TopTop