Xenotransplantation: back to the future?

The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig‐to‐nonhuman‐primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple‐xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.     

Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?

INTRODUCTION: The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. The outcome of 20 liver transplants from Maastricht category 2 NHBD was compared with that of 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support with simultaneous application of chest and abdominal compression (CPS; n = 6) or cardiopulmonary bypass (CPB; n = 14) was used to maintain the donors. RESULTS: At a minimum follow-up of 2 years, actuarial patient and graft survival rates with livers from Maastricht category 2 NHBD were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with organs from HBDs. The graft survival rates was 83% for livers from NHBDs preserved with CPS and 42% in those maintained with CPB.     

Parathyroid resistance to FGF23 in kidney transplant recipients: back to the past or ahead to the future?

Fibroblast growth factor 23 (FGF23) modulates the metabolism of minerals and vitamin D. In chronic kidney disease (CKD), this process is disturbed owing to decreased parathyroid expression of FGF23's receptor complex Klotho-FGF receptor 1. In this issue, Krajisnik and colleagues demonstrate that similar alterations occur in parathyroid glands from kidney transplant recipients in association with a decline in allograft function. Is it possible that these data can be extrapolated to general early-stage CKD patients?     

Are we ready to utilize non-heart-beating donors for clinical allotransplantation in China?

The concept of brain death has not been accepted by the majority of Chinese. Importantly, it is not recognized as a legal entity. We have developed a non-heart-beating donation protocol based on literature searches (Medline, Ovid, and CNKI) and issues related to Chinese customs and ethics. The principles guiding protocol development included: separation of the decision to terminate life support from the donation decision, family-centered donation, freedom of conflict interest, and prohibition of organ sales. This protocol covers donation policy, potential donor identification and evaluation, family consent, determination of death, procurement, and special legal documents/organ distribution policy. A random survey was performed regarding donation. There have been several arguments about the development of this protocol. First, do donor family members have the right to make a decision to withdraw life support? Another issue is whether family members have the right to consent to donation without a will from the donor. Our survey found that over 96.1% of people do not have a will and have not discussed their interests in donation with family members. The last issue is whether the hospital can financially help for the funeral after donation. We have debated these issues nationwide with various opinions. We hope to find the right solutions through international debate. We believe that the use of non-heart-beating-donor organs has potential in China. We are hopeful that it will become a major organ source that is developed in such a way so as to be accepted internationally as well as in China.     

Outcome after admission to ITU following out-of-hospital cardiac arrest: are non-survivors suitable for non-heart-beating organ donation?

We have reviewed retrospective data from two large UK teaching hospitals regarding outcome following out-of-hospital cardiac arrest and the suitability of non-survivors for non-heart-beating organ donation. Patients were selected retrospectively from consecutive admissions from two intensive care units who had presented following out-of-hospital cardiac arrest, to a total of 50 patients in each centre. They had all been resuscitated to achieve a spontaneous cardiac output at the scene, in transit or after arrival in hospital, and required further intensive care support due to cardiovascular, respiratory, or neurological impairment. Eighty-six patients (86%) died in the Intensive Care Unit and only 14 (14%) survived to discharge from the Unit. A further nine (9%) patients died in hospital before discharge home. Four patients (4%) were alive after 6 months and three (3%) were alive after 1 year. Fifty-seven (57%) of patients had active withdrawal of treatment with only four (4%) being potentially suitable for organ procurement having not been excluded because of age, medical history or the length of time to die following withdrawal of treatment. Our results show that only a small increase in donor organs could be potentially achieved from this population. Further work is required to determine whether such patients should be considered as non-heart-beating donors.