Armando Salim Munoz-Abraham

3D Printing of Organs for Transplantation: Where Are We and Where Are We Heading?

In the field of transplantation, the demand for organs continues to increase and has far outpaced the supply. This ever-growing unmet need for organs calls for innovative solutions in order to save more lives. The development of new technologies in the field of biomedical engineering might be able to provide some solutions. With the advent of 3D bioprinting, the potential development of tissues or organ grafts from autologous cells might be within the reach in the near future. Based on the technology and platform used for regular 3D printing, 3D bioprinters have the ability to create biologically functional tissues by dispensing layer after layer of bioink and biogel that if left to mature with the proper environment will produce a functional tissue copy with normal metabolic activity. In the present day, 3D-bioprinted bladders, tracheal grafts, bone, and cartilage have proven to be functional after development and implantation in animal models and humans. Promising ongoing projects in different institutions around the world are focused on the development of 3D-bioprinted organs such as the livers and kidneys with integrated vasculature, in order for the tissue to be able to thrive once it has been transplanted. This review focuses on the background, the present, and the future of 3D bioprinting and its potential role in transplantation.

A new method to measure intestinal secretion using fluorescein isothiocyanate-inulin in small bowel of rats

BACKGROUND Small intestine ischemia can be seen in various conditions such as intestinal transplantation. To further understand the pathologic disruption in ischemia-reperfusion injury, we have developed a method to measure fluid changes in the intestinal lumen of rats. METHODS Two 10-cm rat intestine segments were procured, connected to the terminal apertures of a perfusion device, and continuously infused with 3 mL of HEPES solution (control solution) containing 50 μM of fluorescein isothiocyanate (FITC)-inulin. The perfusion device consists of concentric chambers that contain the perfused bowel segments, which are maintained at 37°C via H₂O bath. The individual chamber has four apertures as follows: two fill and/or drain the surrounding HEPES solution on the blood side of the tissue. The others provide flow of HEPES solution containing FITC-inulin through the lumens. The experimental intestine was infused with the same solution with 100 μM of Forskolin. A pump continuously circulated solutions at 6 mL/min. Samples were collected at 15-min intervals until 150 min and were measured by the nanoflourospectrometer. RESULTS A mean of 6-μM decrease in the FITC-inulin concentration in the Forskolin-treated experimental intestine was observed in comparison with that in the control intestine. The FITC-inulin count dilution in the experimental intestine is a result of an increase of fluid secretion produced by the effect of Forskolin, with P values <0.0001. CONCLUSIONS We demonstrate that it is possible to measure luminal fluid changes over time using our new modified perfusion system along with FITC-inulin to allow real-time determinations of fluid and/or electrolyte movement along the small intestine.

Racial and ethnic disparities in access to and utilization of living donor liver transplants

Living donor liver transplantation (LDLT) is a comparable alternative to deceased donor liver transplantation and can mitigate the risk of dying while waiting for transplant. Although evidence exists of decreased utilization of living donor kidney transplants among racial minorities, little is known about access to LDLT among racial/ethnic minorities. We used Organ Procurement and Transplantation Network/United Network for Organ Sharing data from February 27, 2002 to June 4, 2014 from all adult liver transplant recipients at LDLT‐capable transplant centers to evaluate differential utilization of LDLTs based on race/ethnicity. We then used data from 2 major urban transplant centers to analyze donor inquiries and donor rule‐outs based on racial/ethnic determination. Nationally, of 35,401 total liver transplant recipients performed at a LDLT‐performing transplant center, 2171 (6.1%) received a LDLT. In multivariate generalized estimating equation models, racial/ethnic minorities were significantly less likely to receive LDLTs when compared to white patients. For cholestatic liver disease, the odds ratios of receiving LDLT based on racial/ethnic group for African American, Hispanic, and Asian patients compared to white patients were 0.35 (95% CI, 0.20–0.60), 0.58 (95% CI, 0.34–0.99), and 0.11 (95% CI, 0.02–0.55), respectively. For noncholestatic liver disease, the odds ratios by racial/ethnic group were 0.53 (95% CI, 0.40–0.71), 0.78 (95% CI, 0.64–0.94), and 0.45 (95% CI, 0.33–0.60) respectively. Transplant center‐specific data demonstrated that African American patients received fewer per‐patient donation inquiries than white patients, whereas fewer African American potential donors were ruled out for obesity. In conclusion, racial/ethnic minorities receive a disproportionately low percentage of LDLTs, due in part to fewer initial inquiries by potential donors. This represents a major inequality in access to a vital health care resource and demands outreach to both patients and potential donors. Liver Transpl 21:904‐913, 2015.

De-novo hepatocellular carcinoma after pediatric living donor liver transplantation

De-novo malignancies carry an incidence ranging between 3%-26% after transplant and account for the second highest cause of post-transplant mortality behind cardiovascular disease. While the majority of de-novo malignancies after transplant usually consist of skin cancers, there has been an increasing rate of solid tumor cancers over the last 15 years. Although, recurrence of hepatocellular carcinoma (HCC) is well understood among patients transplanted for HCC, there are increasing reports of de-novo HCC in those transplanted for a non-HCC indication. The proposed pathophysiology for these cases has been mainly connected to the presence of advanced graft fibrosis or cirrhosis and always associated with the presence of hepatitis B or C virus. We report the first known case of de-novo HCC in a recipient, 14 years after a pediatric living related donor liver transplantation for end-stage liver disease due to biliary atresia without the presence of hepatitis B or C virus before and after transplant. We present this case report to increase the awareness of this phenomenon and address on the utility for screening and surveillance of hepatocellular carcinoma among these individuals. One recommendation is to use similar guidelines for screening, diagnosis, and treatment for HCC as those used for primary HCC in the pre-transplant patient, focusing on those recipients who have advanced fibrosis in the allograft, regardless of etiology.

3D Bioprinting in Transplantation

The continued rise in patients suffering from organ failure has raised the need for additional sources for replacement organs to improve the quality of life for these patients. Organ transplantation is the standard of care for end-stage organ disease, and as such, there has been an ever-increasing need worldwide to find suitable grafts for those patients.

Surgical Approach to Abdominal Wall Defects and Hernias in Patients with End Stage Organ Disease and Transplantation

Abdominal wall hernias are one of the most common pathologies seen in the surgical world. Over one million abdominal hernia repairs take place in the USA every year. Abdominal wall defects represent a difficult challenge in patients with End Stage Organ Disease (ESOD) particularly those who suffer from chronic liver disease. Ascites, malnutrition, and increased abdominal pressure are some of the factors that predispose them to a greater risk for developing abdominal wall defects, in a population that in most cases are not ideal candidates for surgery. Recipients of abdominal organs, specifically after liver transplantation, are known to have a much higher risk of developing incisional hernias. In many series the incidence can be greater than 20%. Factors prompting to the development of a wall defect vary from patient to patient; the location and complexity of the defect, administration of immunosuppression, post-transplant complications, and the specific anatomy of the different incisions play a key role in the classification and risk stratification.

Host factors are dominant in the development of post-liver transplant non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is a recognized problem in patients after orthotopic liver transplantation and may lead to recurrent graft injury. As the increased demand for liver allografts fail to match the available supply of donor organs, split liver transplantation (SLT) has emerged as an important technique to increase the supply of liver grafts. SLT allows two transplants to occur from one donor organ, and provides a unique model for observing the pathogenesis of NAFLD with respect to the role of recipient environmental and genetic factors. Here we report on two recipients of a SLT from the same deceased donor where only one developed non-alcoholic steatohepatitis (NASH), suggesting that host factors are critical for the development of NASH.