Investigation of the differentiation potential of pericyte cells as an alternative source of mesenchymal stem cells.

BACKGROUND: The mesenchymal stem cells (MSCs) with characterized by their multipotency and capacity to differentiate into various tissue cell types, have led to their incorporation in regenerative medicine research. However, the limited numbers of MSCs in the human body and their diverse differentiation capabilities in tissues highlight the need for exploring alternative regenerative cell sources. In this study, therefore, we conducted molecular level examinations to determine whether pericytes, specialized cell communities situated near blood vessels, could serve as a substitute for human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this context, the potential application of pericytes surrounds the vessels when MSCs are insufficient for functional purposes. METHODS: The pericytes utilized in this investigation were derived from the placenta and characterized at the third passage. Similarly, the hBM-MSCs were also characterized at the third passage. The pluripotent properties of the two cell types were assessed at the gene expression level. Thereafter, both pericytes and hBM-MSCs were directed towards adipogenic, osteogenic and chondrogenic differentiation. The cells in both groups were examined on days 7, 14, and, 21 and their differentiation status was compared both immunohistochemically and through gene expression analysis. RESULTS: Upon comparing the pluripotency characteristics of placental pericytes and hBM-MSCs, it was discovered that there was a substantial upregulation of the pluripotency genes FoxD3, Sox2, ZPF42, UTF1, and, Lin28 in both cell types. However, no significant expression of the genes Msx1, Nr6a1, Pdx1, and, GATA6 was observed in either cell type. It was also noted that pericytes differentiate into adipogenic, osteogenic and, chondrogenic lineages similar to hBM-MSCs. DISCUSSION: As a result, it has been determined that pericytes exhibit high differentiation and proliferation properties similar to those of MSCs, and therefore can be considered a suitable alternative cell source for regenerative medicine and tissue engineering research, in cases where MSCs are not available or insufficient. It is notable that pericytes have been suggested as a potential substitute in studies where MSCs are lacking.

Investigation of impacts of decellularized heart extracellular matrix and VEGF on cardiomyogenic differentiation of mesenchymal stem cell through Notch/Hedgehog signaling pathways.

OBJECTIVE: Decellularization is the process to obtain natural scaffolds with tissue integrity and extracellular matrix components, and recellularization is used to produce tissue-like constructs with specific cell types. In this study, rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) were cultured on decellularized heart extracellular matrix. These cells were then induced to differentiate into cardiomyogenic cells under the stimulatory effect of vascular endothelial growth factor (VEGF) and other chemicals. This study aimed to investigate the effect of the cardiac extracellular matrix and VEGF on cardiomyogenic differentiation in the context of the Notch and Hedgehog signaling pathways. METHODS: Heart samples extracted from rats were decellularized by serial application of detergent to remove cells from the tissue, and then recellularized with rBM-MSCs. The recellularized tissue matrices were then analyzed for cardiomyogenesis. Cardiomyogenic differentiation was performed on decellularized heart extracellular matrix (ECM; three-dimensional scaffolds) and culture plates (two-dimensional cell culture system) for 28 days to understand the effects of the heart extracellular matrix. In addition, differentiation was induced with and without the stimulatory effect of VEGF to understand the effect of VEGF on cardiomyogenic differentiation of rBM-MSCs. RESULTS: Immunofluorescence staining showed that decellularization of the heart was performed effectively and successfully. After decellularization process, the heart extracellular matrix was completely free of cells. It was observed that rBM-MSCs transplanted onto the heart extracellular matrix remained viable and proliferated for 21 days after recellularization. The rBM-MSCs promoted cardiomyogenic differentiation in the conventional differentiation medium but were inversely affected by both VEGF and heart extracellular matrix proteins. Lower expression of connexin43 and cardiac troponin I genes was observed in cells induced by either matrix proteins or VEGF, compared to cells differentiated by chemical agents alone. CONCLUSION: In this study, we investigated the effect of decellularized heart extracellular matrix and VEGF on cardiomyogenic differentiation of rBM-MSCs. On the decellularized cardiac extracellular matrix, rBM-MSCs maintained their viability by adhering to the matrix and proliferating further. The adhesion of the cells to the matrix also produced a physical stimulus that led to the formation of histological structures resembling myocardial layers. Chemical stimulation of the decellularized heart extracellular matrix and cardiomyogenic differentiation supplements resulted in increased expression of cardiomyogenic biomarkers through modulation of the Notch and Hedgehog signaling pathways.

Reduced-Size Left Lateral Segment Grafts in Infants Weighing <10 kg.

BACKGROUND: Live donor liver transplantation for infants weighing <10 kg has unique complexities, as patient/graft size discrepancies may cause vascular perfusion deficiencies. Failure of the abdominal closure further complicates this already challenging procedure. To overcome these potential problems, several techniques for graft size reduction-either anatomic or nonanatomic-have been proposed in the literature. Technically easier and less time-consuming, nonanatomic size reductions have the advantage of avoiding the risk of injury to the portal pedicle. This study aimed to evaluate and compare the effects of nonanatomic graft size reduction in infants weighing <10 kg with a large estimated preoperative graft recipient weight ratio. METHODS: We enrolled 106 infants weighing <10 kg. Of these infants, 50 received reduced-size grafts. The outcomes were compared between the groups. RESULTS: No difference was observed between the groups according to survival and vascular or biliary complications. None of the patients required an open abdomen or mesh closure. CONCLUSION: Nonanatomic size reduction of left lateral segment grafts can be safely applied without compromising vascular supply, graft function, and patient survival with comparable vascular and biliary complication rates. This technique is safe and efficient in overcoming the complications caused by large-for-size syndrome in infants weighing <10 kg.

Investigation of the effect of pancreatic decellularized matrix on encapsulated Islets of Langerhans with mesenchymal stem cells.

OBJECTIVE: In this study, it was aimed to provide a therapeutic approach for T1DM by encapsulating the pancreatic islets with mesenchymal stem cells and decellularized pancreatic extracellular matrix to support the survival of islets while maintaining their cellular activity. METHOD: Pancreatic extracellular matrix was decellularized using different concentrations of detergent series. After the preparation of the protein-based tissue extracellular matrix was shown to be free of cells or any genetic material by molecular, immunofluorescence and histochemical techniques. Following the homogenization of the decellularized pancreatic extracellular matrix and the analysis of its protein composition by LC-MS, the matrix proteins were incorporated with pancreatic islets and rat adipose tissue-derived MSCs (rAT-MSCs) in alginate microcapsules. Glucose-stimulated insulin secretion property of the islet cells in the microbeads was evaluated by insulin ELISA. The gene expression profile of the encapsulated cells was analyzed by Real-Time PCR. RESULTS: Unlike the protein composition of whole pancreatic tissue, the decellularized pancreas matrix was free of histone proteins or proteins originated from mitochondria. The protein matrix derived from pancreatic tissue was shown to support the growth and maintenance of the islet cells. When compared to the non-encapsulated pancreatic islet, the encapsulated cells demonstrate to be more efficient in terms of insulin expression. CONCLUSION: The extracellular pancreatic matrix obtained in this study was directly used as supplementary in the alginate-based microcapsule enhancing the cell survival. The tissue matrix protein and alginate had a synergistic effect on total insulin secretion, which might have the potential to overcome the insulin deficiency. Despite the improvement in the cell viability and the number, the efficiency of the insulin secretion in response to glucose stimulation from the alginate microcapsules did not meet the expectation when compared with the non-encapsulated pancreatic islets.

Portal Vein Pull-Through Technique and Thrombectomy for Extensive Portal Vein Thrombosis.

BACKGROUND: Herein, a different technique is presented describing complete dissection of the entire portal vein (PV), superior mesenteric vein (SMV), and splenic vein, thus enabling a complete thrombectomy without the risk of uncontrolled hemorrhage due to blind thrombectomy. METHODS: In cases where a thrombectomy would not be an option because of extensive thrombosis involving the confluence of the PV and SMV, small branches of the SMV, including the inferior mesenteric vein, were divided. Both the SMV and splenic vein were encircled separately. Then, the side branches of the PV above the pancreas, left gastric vein on the left side, and superior pancreatoduodenal vein on the right side were divided. The lateral and posterior part of the PV were dissected within the pancreas both from above and below, allowing the main PV completely free from attachments. At this point, the splenic vein and SMV were clamped, and the main PV was divided above the pancreas and then pulled back through the pancreatic tunnel. The thrombus was easily dissected of the vein under direct visualization, and afterward the PV was redirected to its original position. Then, the liver transplant was carried out in a regular fashion. RESULTS: This technique was applied to 2 patients. The first was a 43-year-old man who underwent a right lobe living donor liver transplant because of hepatitis B virus-related cirrhosis. The patient is still alive and well with stable liver function after 15 years of follow-up. The second was a 69-year-old woman who underwent a right lobe living donor liver transplant because of hepatitis C virus and hepatocellular carcinoma. She survived the procedure and her liver function was entirely normal afterward. She died of pneumonia and sepsis 5 months after transplant. CONCLUSIONS: This technique enables complete dissection of the entire PV, SMV, and splenic vein. Thus, complete thrombectomy under direct visualization without the risk of uncontrolled hemorrhage can be performed.

Resveratrol improves vascular endothelial dysfunction in the unpredictable chronic mild stress model of depression in rats by reducing inflammation.

Chronic psychological stress may cause depression and it is a risk factor for vascular endothelial dysfunction. Inflammation may contribute to endothelial dysfunction. Resveratrol, which has antiinflammatory and vasculoprotective properties, has been reported its beneficial effects on endothelial dysfunction induced by hypertension, diabetes and, aging. The effects of resveratrol on stress-induced endothelial dysfunction is not investigated yet. This study aimed to investigate the efficacy of resveratrol on vascular function in the unpredictable chronic moderate stress (UCMS) model of rats and to examine the possible mechanisms of resveratrol by assessment of proinflammatory markers. Male rats were assigned to 4 groups (n = 8 for each group): Control, Control+Resveratrol, UCMS, UCMS+Resveratrol. UCMS and UCMS+Resveratrol groups were exposed to the UCMS procedure for 12 weeks. Resveratrol (20 mg/kg/day, i.p., during 12 weeks) was given to the Control+Resveratrol and UCMS+Resveratrol groups.Then depressive-like behaviors were evaluated by forced swimming test. After behavioral tests, systolic blood pressure was recorded. Endothelial function of the thoracic aorta was evaluated by isolated organ bath system. Vascular eNOS expression and inflammatory markers such as TNF-α, IL-1ß, IL-6, CRP, ICAM1, MCP in serum and vascular tissue were analyzed to explore the mechanisms of resveratrol. UCMS resulted in depressive-like behavior, endothelial dysfunction and increased inflammatory cytokines in both serum and tissue samples. Resveratrol treatment improved depressive-like behavior, ameliorated vascular dysfunction, and reversed stress-induced inflammation. Our findings suggest that resveratrol exerted antidepressant-like effect and prevented vascular endothelial dysfunction by reducing systemic and peripheral inflammation in UCMS-induced depression in rats. Therefore, resveratrol may be a therapeutic option with a vasculoprotective effect in depression.

Bilioenteric Reconstruction Techniques in Pediatric Living Donor Liver Transplantation.

Biliary complications (BCs) are still a major cause of morbidity following liver transplantation despite the advancements in the surgical technique. Although Roux-en-Y (RY) hepaticojejunostomy has been the standard technique for years in pediatric patients, there is a limited number of reports on the feasibility of duct-to-duct (DD) anastomosis, and those reports have controversial outcomes. With the largest number of patients ever reported on the topic, this study aims to discuss the feasibility of the DD biliary reconstruction technique in pediatric living donor liver transplantation (LDLT). After the exclusion of the patients with biliary atresia, patients who received either deceased donor or right lobe grafts, and retransplantation patients, data from 154 pediatric LDLTs were retrospectively analyzed. Patients were grouped according to the applied biliary reconstruction technique, and the groups were compared using BCs as the outcome. The overall BC rate was 13% (n = 20), and the groups showed no significant difference (P = 0.6). Stricture was more frequent in the DD reconstruction group; however, this was not statistically significant (P = 0.6). The rate of bile leak was also similar in both groups (P = 0.6). The results show that the DD reconstruction technique can achieve similar outcomes when compared with RY anastomosis. Because DD reconstruction is a more physiological way of establishing bilioenteric integrity, it can safely be applied.

Hepatic Venous Outflow Reconstruction Directly Into the Right Atrium.

OBJECTIVES: Living-donor liver transplant for BuddChiari syndrome is particularly challenging because of the need for venous outflow reconstruction as grafts from living donors lack vena cava. In addition, recipient vena cava may be thrombotic and fibrotic to such an extent that it would not allow graft venous outflow reconstruction. Under these circumstances, the right atrium provides an easily accessible alternative for venous outflow reconstruction, omitting the need for vena cava replacement. MATERIALS AND METHODS: Data from 3 patients who were treated using this technique were collected and evaluated with regard to surgical technique and outcomes. RESULTS: All patients were alive without vascular complications after a mean follow-up of 67 months. The applied surgicaltechnique was similar except with regard to vena cava preservation. CONCLUSIONS: During the natural course of the disease, venous collaterals form as chronic thrombosis extends into the vena cava. The vena cava can be safely resected in these patients to facilitate hepatectomy through dense adhesions, which is another common clinical problem in this disease. Consequently, venous outflow reconstruction to the right atrium creates the feasible opportunity of draining the graftliver without having to replace the vena cava.

A rare location of benign osteoblastoma: review of the literature and report of a case.

Benign osteoblastoma is a rare primary bone tumor that constitutes approximately 1% of all primary bone tumors. Its occurrence in the craniomaxillofacial region as also rare and represents only 15% of all osteoblastomas. The tumor shows a predilection for the male gender and constitutes less than 1% of all tumors of the maxillofacial region. In the maxillofacial region, the mandible is affected more frequently than the maxilla, and the coronoid process of the mandible is the area most rarely affected by osteoblastoma. Before this report, 53 cases have been reported in the literature. In this report, a rare location of osteoblastoma, namely, the coronoid process of the mandible, is described.

Benign osteoma with Gardner syndrome: review of the literature and report of a case.

Gardner syndrome, a variant of familial adenomatous polyposis, is an autosomal dominant disease characterized by gastrointestinal polyps that develop in the colon as well as in the stomach and upper intestine (duodenum), multiple osteomas, and skin and soft tissue tumors. Cutaneous findings include epidermoid cysts, desmoid tumors, and other benign tumors. Polyps have a 100% risk of undergoing malignant transformation; consequently, early identification and therapy of the disease are critical. Osteoma is a benign neoplasm of bone tissue that is characterized by slow continuous growth and is the most common accompanying bone lesion seen in Gardner syndrome. The authors report a case of Gardner syndrome that was operated on because of the mandibular osteoma.