RGM.20.003 – Bioengineering of donor organs through pre-transplant ex vivo perfusion
With an aging population and rising healthcare costs, the need for personalized strategies in medicine has grown considerably. In this context, regulation of gene expression or gene editing represents tailor-made solutions to help the body to repair and regenerate itself. In addition, transplant bioengineering may allow preventing undesirable processes or immune responses that may lead to rejection after transplantation. In the field of organ transplantation, ex-vivo perfusion provides a perfect and highly controllable environment for interventions to an isolated organ donor prior to transplantation. Many essential physiological parameters can be artificially manipulated, thus creating the optimal conditions for actively and permanently altering the graft’s genome by means of various gene therapy approaches, without exposing a whole patient to potential risks and side-effects of bioengineering. Immunoresponse and ischemia reperfusion (I/R) injury still represent crucial hurdles in transplantation and main causes of transplant failure. Targets of the genetic modification approach have already been identified and include for example silencing Human Leukocyte Antigen (HLA) expression, endothelial modification to induce post-transplant operational tolerance, as well as gene therapeutic interventions in ischemia/reperfusion mechanisms, which could protect the organ from acute transplant-related injury. Further targets could be identified using (animal) models of transplantation injury/inflammation and could be validated during ex-vivo perfusion. To capture the full potential of this innovative regenerative medicine programme, a synergistic and multidisciplinary effort is pivotal. To this regard, the interdisciplinary approach of this research consortium will be ensured by the participation of (academic and non-academic ) experts in the different fields of transplantation, spanning from basic/fundamental science to clinical application, which will form the optimal ground for future implementation and use of findings.
bioengineering, ex vivo organ perfusion, kidney transplantation
Germany, Medizinische Hochschule Hannover
|Organisation||University Medical Center Groningen (UMCG)|
|Name||Dr. C. (Cyril) Moers|