Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice

BACKGROUND：Cell therapy has been promising for various diseases.We investigated whether transplantation of human umbilical cord mesenchymal stem cells（h UCMSCs）has any therapeutic effects on D-galactosamine/lipopolysaccharide（Gal N/LPS）-induced fulminant hepatic failure in mice.METHODS：h UCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with Gal N/LPS-induced fulminant hepatic failure.After transplantation,the localization and differentiation of h UCMSCs in the injured livers were investigated by immunohistochemical and genetic analy- ses. The recovery of the injured livers was evaluated histologi- cally. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test. RESULTS： hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adip- ogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the for- mation of hUCMSCs-derived hepatocyte-like cells in vivo.CONCLUSIONS： hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUC- MSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND： The established procedure for ABO-incompatible liver transplantation（ABO-I LT） was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin（IVIG） for ABO-I LT in patients with acute liver failure（ALF）.METHODS： The data from 101 patients who had undergone liver transplantation（LT） for ALF were retrospectively analyzed.The patients were divided into two groups： ABO-compatible liver transplantation group（ABO-C LT, n=66） and ABO-I LT group（n=35）. All the patients in the ABO-I LT group received a single dose of rituximab（375 mg/m2） and IVIG（0.4 g/kg per day） at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol.Quadruple immunosuppressive therapy including basiliximab,corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.RESULTS： The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%,respectively（P〉0.05）, and the graft survival rates were 80.0%and 86.3%, respectively（P〉0.05）. Two patients（5.7%） suffered from antibody-mediated rejection in the ABO-I LT group.Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.CONCLUSIONS： The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Feasibility of ABO-incompatible adult living donor liver transplantation for acute-on-chronic liver failure

To the Editor:In Korea,the annual number of deceased donors for or gan transplantation per million people is still less than10.Thus,approximately 40%of patients with acute liver failure or acute-on-chronic liver failure undergo living donor liver transplantation（LDLT）.;Although the use of ABO-incompatible（ABOi）living donors is an attrac tive option,ABOi LDLT has very restricted applications

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of < 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration < 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.

Management of intestinal failure in inflammatory bowel disease:Small intestinal transplantation or home parenteral nutrition?

Inflammatory bowel disease and Crohn&#x02019;s disease in particular, is a common cause of intestinal failure. Current therapeutic options include home parenteral nutrition and intestinal transplantation. For most patients, home intravenous therapy including parenteral nutrition, with a good probability of long-term survival, is the favoured choice. However, in selected patients, with specific features that may shorten survival or complicate home parenteral nutrition, intestinal transplantation presents a viable alternative. We present survival, complications, quality of life and economic considerations that currently influence individualised decision-making between home parenteral nutrition and intestinal transplantation.

Management of patients with a failed kidney transplant: Dialysis reinitiation, immunosuppression weaning, and transplantectomy

The number of patients reinitiating dialysis after a failed transplant increases over time and has more than doubled between the year 1988 and 2010 （an increase from 2463 to 5588）. More importantly, patients returning to dialysis have been shown to have a greater thanthree-fold increase in the annual adjusted mortality rates compared with those with a functioning graft. Continuation of immunosuppression to preserve residual graft function has been implicated to be a contributing factor, seemingly due to immunosuppression-ass-ociated cardiovascular and infectious complications and malignancy risk, among others. Nonetheless, maintenance low-dose immunosuppression has been suggested to confer survival beneft in patients returning to peritoneal dialysis. Whether early vs late reinitiation of dialysis or whether transplantectomy has an impact on patient survival remains poorly defined. Consensus guidelines for the management of a failed allograft are lacking. In this article, we present a literature overview on the ideal timing of dialysis reinitiation after graft loss, the management of immunosuppression after graft failure, and the risks and benefits of transplantectomy. The authors’ perspectives on the management of this special patient population are also discussed.

Classic Ehlers-Danlos syndrome and cardiac transplantation-Is there a connection?

Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.

Kidney transplantation after liver transplantation

Kidney transplantation after liver transplanta tion（KALT） offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efficacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta tion because of calcineurin inhibitor（CNI）-induced neph rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.

Adult to adult living related liver transplantation: Where do we currently stand?

Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers.

Patients 60 Years of Age and Older Should Have the Same Chance for Heart Transplantation or Not?

Heart transplantation is considered the best treatment modality for advanced heart disease. While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse effect of advanced age, however donor hearts＇ shortage continues to stimulate the discussion about the recipient＇s upper age limit. Our study was based on a retrospective analysis for the results of 52（18%） patients aged 60 years and older undergoing heart transplantation between May 2008 and December 2015, and these patients were compared with 236（82%） adult recipients who were younger than 60 years at the time of transplantation and during the same period. In older group, 71% were males with the mean age of 63.38±3.55 years, and in younger group, 83.4% were males with a mean age of 43.72±11.41 years（P=0.27）. Dilated cardiomyopathy was the most common indication for transplantation among patients in both groups（P=0.147）. In older group, the 3-month survival rate was higher than that in younger group（P=0.587）, however the 6-month survival rate showed no significant difference（P=0.225）. Although the 1-year survival rate was higher in older group（P=0.56）, yet the 3-year survival rate between the two groups showed no statistically significant difference（P=0.48）. According to our experience among older heart transplant candidates who were 60 years and older, we believe that advanced age should not be an excluding criterion to cardiac transplantation.

Early graft failure after meniscus allograft transplantation： an unusual cause of using all-inside meniscal repair device

Meniscal allograft transplantation （MAT） may offer .an attractive alternative to restore the normal biomechanical structure of knees. The mean early failure rate （≤2 years） of MAT is approximately 10%.1-3 A successful outcome of MAT depends on the ligamentous stability of knee, limb alignment, graft types, and graft fixation methodsY Graft fixations include the meniscal horns and the peripheral rim. Techniques for fixation of the peripheral rim include sutures or a meniscal repair device such as FasT-Fix （Smith ＆ Nephew Inc, Andover, MA, USA）. Here we present an unusual case of early graft failure using FasT-Fix sutured to the peripheral rim of the graft.