Neural stem cell transplantation in a double-layer collagen membrane with unequal pore sizes for spinal cord injury repair

A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-μm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and signiifcantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental ifndings suggest that the transplantation of neural stem cells in a double-lay-er collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.

Combined transplantation of GDAs^(BMP) and hr-decorin in spinal cord contusion repair

Following spinal cord injury, astrocyte proliferation and scar formation are the main factors inhibiting the regeneration and growth of spinal cord axons. Recombinant decorin suppresses inflammatory reactions, inhibits glial scar formation, and promotes axonal growth. Rat models of T8 spinal cord contusion were created with the NYU impactor and these models were subjected to combined transplantation of bone morphogenetic protein-4-induced glial-restricted precursor-derived astro- cytes and human recombinant decorin transplantation. At 28 days after spinal cord contusion, dou- ble-immunofluorescent histochemistry revealed that combined transplantation inhibited the early in- flammatory response in injured rats. Furthermore, brain-derived neurotrophic factor, which was se- creted by transplanted cells, protected injured axons. The combined transplantation promoted ax- onal regeneration and growth of injured motor and sensory neurons by inhibiting astrocyte prolif- eration and glial scar formation, with astrocytes forming a linear arrangement in the contused spinal cord, thus providing axonal regeneration channels.

Biliary obstruction following transjugular intrahepatic portosystemic shunt placement in a patient after liver transplantation:A case report

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is a method used to decrease portal hypertension.Biliary stricture is the rarest of the complications associated with this procedure with only 12 cases previously reported in the literature.None of these cases have documented the resolution of biliary stenosis induced by a stent graft.The only curative solutions reported are liver transplantation or bypassing the stenosis with an artificial biliary tract using advanced endoscopic techniques.CASE SUMMARY This is the first reported case of biliary obstruction secondary to TIPS placement in a transplanted liver.In our patient,a portosystemic shunt was created to treat severe veno-occlusive liver graft disease manifesting itself primarily by fluid retention.A cholestatic liver lesion and cholangitis with abscesses developed due to a stent graft-induced stricture in the dorsal segment of the right hepatic duct and the stricture diminished following percutaneous drainage.Endoscopic drainage was performed after unsuccessful removal of the percutaneous catheter resulting in a bilio-cutaneous fistula.Although the liver graft now functions well,the stricture remains refractory even after 44 mo of treatment.CONCLUSION Biliary strictures caused by TIPS in both transplanted and native livers seem refractory to endoscopic treatment.

Challenges of recurrent hepatitis C in the liver transplant patient

Cirrhosis secondary to hepatitis C virus(HCV)is a very common indication for liver transplant.Unfortunately recurrence of HCV is almost universal in patients who are viremic at the time of transplant.The progression of fibrosis has been shown to be more rapid in the post-transplant patients than in the transplant na?ve,hence treatment of recurrent HCV needs to be considered for all patients with documented recurrent HCV.Management of recurrent HCV is a challenging situation both for patients and physicians due to multiple reasons as discussed in this review.The standard HCV treatment with pegylated interferon and Ribavarin can be considered in these patients but it leads to a lower rate of sustained virologic clearance than in the nontransplanted population.Some of the main challenges associated with treating recurrent HCV in post-transplant patients include the presence of cytopenias;need to monitor drug-drug interactions and the increased incidence of renal compromise.In spite of these obstacles all patients with recurrent HCV should be considered for treatment since it is associated with improve-ment in survival and a delay in fibrosis progression.With the arrival of direct acting antiviral drugs there is renewed hope for better outcomes in the treatment of post-transplant HCV recurrence.This review evaluates current literature on this topic and identifies challenges associated with the management of post-transplant HCV recurrence.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims: To evaluate the effect of intrapar-enchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Methods: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. Results: On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplanta-tion, consistent with structural improvements in mitochondria and nuclear compartments. Conclusions: Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

The aim of this study is to explore the effective-ness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus.A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities.The dia-gnosis of pemphigus was made on the basis of the clinical,histologic and immunofluorescence findings.The patient had shown resistance to conventional therapy with gluco-corticoid and immunosuppressive agents.Two months before admission,he complained of hip joint pain.X-ray and CT scan revealed aseptic necrosis of the femoral head.Stem-cell mobilization was achieved by treatment with cyclophosphamide,granulocyte colony-stimulating factor(G-CSF)and rituximab.Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use.Immunoablation was accomplished by using cyclophospha-mide(200 mg/kg;divided into 50 mg/kg on days-5,-4,-3,and-2),antithymocyte globulin(ATG;10 mg/kg;divided into 2.5 mg/kg on days-6,-5,-4,and-3),and rituximab(1200 mg/d;divided into 600 mg/d on days 0 and 7).Autologous peripheral hematopoietic stem cell transplanta-tion was followed by reconstitution of the immune system which was monitored by flow cytometry.The glucocorti-coid was withdrawn immediately after transplantation.The pemphigus titer turned negative 6 weeks after transplanta-tion and remained negative.The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up.The patient’s response suggests that autologous peri-pheral hematopoietic stem cell transplantation may be a potential“cure”for refractory pemphigus.However,fur-ther studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resist-ance to conventional therapy.

Extensor digitorum brevis and extensor hallusis brevis transplantation for treatment of long-standing facial pa-ralysis

Objective: To evaluate the efficacy of free transplan-tation of denervated muscles and vessels in the treatment of long-standing facial paralysis.Methods: A total of 26 patients with facial paralysis (10 males and 16 females, aged 16-65 years, mean: 47 years) were enrolled in this study to receive transplantation of denervated extensor digitorum brevis (EDB) and extensor hallusis brevis (EHB). The muscle tendon was slung to the ala nasi, the middle point of the nasolabial sulcus, the angu-lus otis and the chin to correct the nasal and oral deformity. The muscle belly was buried around the nerves that inner-vated the masseter muscle. Microsurgery was applied to anastomosing the tarsus lateral vessels to the superficial temporalis vessels.Results: After operation, all the patients immediately obtained satisfied static appearance. The movement of the paralyzed comer of the mouth could be obtained one month later and the smile of the paralyzed side could be restored after 3 months of training. And 88% patients achieved per-fect results, 8% obtained satisfactory results, and 4% got improvement 6 months after operation according to Stennert's paresis scoring system.Conclusions: Free transplantation of denervated muscles and vessels for the treatment of long-standing fa-cial paralysis, which seldom causes atrophy or liquefaction of the transferred muscles, can maintain muscle viability and induce reliable nerve regeneration. Therefore, it is a safe and efficient treatment method for the patients suffer-ing from facial paralysis.