Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety

Background: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. Methods: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. Results: The number and percent of donors with drug use has significantly increased over the study period ( P <0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival ( P <0.0001). Conclusions: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

Proliferation Increasing Genetic Engineering in Human Corneal Endothelial Cells: A Literature Review

The corneal endothelium is the inner layer of the cornea. Despite comprising only a monolayer of cells, dysfunction of this layer renders millions of people visually impaired worldwide. Currently, corneal endothelial transplantation is the only viable means of restoring vision for these patients. However, because the supply of corneal endothelial grafts does not meet the demand, many patients remain on waiting lists, or are not treated at all. Possible alternative treatment strategies include intracameral injection of human corneal endothelial cells (HCEnCs), biomedical engineering of endothelial grafts and increasing the HCEnC density on grafts that would otherwise have been unsuitable for transplantation. Unfortunately, the limited proliferative capacity of HCEnCs proves to be a major bottleneck to make these alternatives beneficial. To tackle this constraint, proliferation enhancing genetic engineering is being investigated. This review presents the diverse array of genes that have been targeted by different genetic engineering strategies to increase the proliferative capacity of HCEnCs and their relevance for clinical and research applications. Together these proliferation-related genes form the basis to obtain a stable and safe supply of HCEnCs that can tackle the corneal endothelial donor shortage.

Thoracic Organ Procurement during Multi-Organ Retrieval

Procurement of thoracic organs can be divided into two major categories- donation after brain death (DBD) or donation after circulatory determination of death (DCDD). In this section we will focus primarily on DBD, which is the commoner of these two or at times referred to as standard procurement. DCDD is a relatively new and promising field that has helped ameliorate donor shortage, aided by the latest advances in medical technology. However, DBD continues to be the major avenue of organ donation. There are several different combinations of thoracic procurement surgeries: heart, double lung, single lung/ 2-single lungs, heart-lung en bloc for transplantation, Double Lung procurement for Bronchial arterial revascularization, Heart and Lung procurement in DCDD donors with the OCS, NRP or Lungs for EVLP.

Preliminary studies of constructing a tissue-engineered lamellar corneal graft by culturing mesenchymal stem cells onto decellularized corneal matrix

AIM: To construct a competent corneal lamellar substitute in order to alleviate the shortage of human corneal donor. METHODS: Rabbit mesenchymal stem cells (MSCs) were isolated from bone marrow and identified by flow cytometric, osteogenic and adipogenic induction. Xenogenic decellularized corneal matrix (XDCM) was generated from dog corneas. MSCs were seeded and cultured on XDCM to construct the tissue-engineered cornea. Post-transplantation biocompatibility of engineered corneal graft were tested by animal experiment. Rabbits were divided into two groups then underwent lamellar keratoplasty (LK) with different corneal grafts: 1) XDCM group (n=5): XDCM; 2) XDCM-MSCs groups (n=4): tissue-engineered cornea made up with XDCM and MSCs. The ocular surface recovery procedure was observed while corneal transparency, neovascularization and epithelium defection were measured and compared. In vivo on focal exam was performed 3mo postoperatively. RESULTS: Rabbit MSCs were isolated and identified. Flow cytometry demonstrated isolated cells were CD90 positive and CD34, CD45 negative. Osteogenic and adipogenic induction verified their multipotent abilities. MSC-XDCM grafts were constructed and observed. In vivo transplantation showed the neovascularization in XDCM-MSC group was much less than that in XDCM group postoperatively. Post-transplant 3-month confocal test showed less nerve regeneration and bigger cell-absent area in XDCM-MSC group. CONCLUSION: This study present a novel corneal tissue-engineered graft that could reduce post-operatively neovascularization and remain transparency, meanwhile shows that co-transplantation of MSCs may help increase corneal transplantation successful rate and enlarge the source range of corneal substitute to overcome cornea donor shortage.

Intermediate outcomes of right-to-left inverted living-donor lobar lung transplantation

OBJECTIVESOwing to the severe donor shortage in Japan, living-donor lobar lung transplantation (LDLLT) remains a valuable option. As only lobes are implanted in LDLLT, grafts may be too small, especially for adult recipients. To overcome this obstacle, we developed right-to-left inverted LDLLT. In this procedure, the right lower lobe, which is 25% bigger than the left lower lobe, is used as the left-side graft instead of the left lower lobe. This study aimed to investigate the characteristics and intermediate outcomes of right-to-left inverted LDLLT.METHODSSince the first right-to-left inverted LDLLT performed in 2014, 48 LDLLTs have been performed in our institution, of which 15 were right-to-left inverted LDLLTs. We reviewed their characteristics and intermediate outcomes.RESULTSThe reasons for choosing an inverted procedure instead of the standard LDLLT were small-for-size graft in 11 cases and anatomical variation of donor vessels in 4 cases. The first patient underwent left single LDLLT using a right lower lobe graft, and the following 14 patients underwent bilateral LDLLT using 2 right lower lobe grafts. A native upper lobe-sparing procedure was additionally applied in 2 patients. No complications occurred in the bronchial and vascular anastomoses. No operative mortality occurred, and all the patients were discharged home after LDLLT. The 3-year survival was 92.3%, with a median follow-up time of 40 months. The donor postoperative course was uneventful, and all the donors returned to their regular routine postoperatively.CONCLUSIONRight-to-left inverted LDLLT is a safe and useful option with encouraging intermediate outcome.

Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.

Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.