Organogenesis最新文献

The development and repair of dentin are strictly regulated by hundreds of genes. Abnormal dentin development is directly caused by gene mutations and dysregulation. Understanding and mastering this signal network is of great significance to the study of tooth development, tissue regeneration, aging, and repair and the treatment of dental diseases. It is necessary to understand the formation and repair mechanism of dentin in order to better treat the dentin lesions caused by various abnormal properties, whether it is to explore the reasons for the formation of dentin defects or to develop clinical drugs to strengthen the method of repairing dentin. Molecular biology of genes related to dentin development and repair are the most important basis for future research.

Work toward renal generation generally aims either to introduce suspensions of stem cells into kidneys in the hope that they will rebuild damaged tissue, or to construct complete new kidneys from stem cells with the aim of transplanting the engineered organs. In principle, there might be a third approach; to engineer renal tissue 'modules' in vitro and to use them to replace sections of damaged host kidney. This approach would require the urine collecting system or ureter of the new tissues to connect to those of the host. In this report, we demonstrate a method that allows collecting duct trees or ureters, engineered from ES cells, to connect to the collecting duct system or ureter, respectively, of fetal kidneys in culture.

The use of primary human hepatocytes has been hampered by limited availability of adequate numbers of fresh and viable cells due to the ongoing shortage of liver donors. Thus, there is no surplus of healthy organs from which freshly isolated cells can be prepared when needed. However, primary hepatocytes can be successfully isolated from explanted liver specimens obtained from patients receiving orthotopic liver transplantation for decompensated liver cirrhosis or for metabolic liver disease without end-stage liver disease and are a valuable resource for the pharmaceutical industry research. This review focuses on the isolation, characterization and cryopreservation of hepatocytes derived from therapeutically resected livers with various hepatic diseases.

To develop a tissue-engineered vascular graft, we used pericardial effusion-derived progenitor cells (PEPCs) collected from drained fluid after open-heart surgery in children with congenital heart diseases to repopulate a decellularized porcine pulmonary artery. The PEPCs were compared with human fibroblasts (HS68) and human umbilical vein endothelial cells (HUVECs) in cell growth and migration. They were cultured with the matrices via an inner approach (intima), lateral approach (media), and outer approach (adventitia). PEPCs grew and migrated better than the other two cells 14 days after seeding in the decellularized vessel. In immunofluorescence assays, PEPCs expressed CD90 and CD105 indicating a vascular differentiation. PEPCs grew in a decellularized porcine pulmonary artery matrix may have the potential for producing tissue-engineered vascular grafts.

Cartilage and joint damage easily degenerates cartilage and turns into osteoarthritis (OA), which seriously affects human life and work, and has no cure currently. The temporal and spatial changes of multiple microenvironments upon the damage of cartilage and joint are noticed, including the emergences of inflammation, bone remodeling, blood vessels, and nerves, as well as alterations of extracellular and pericellular matrix, oxygen tension, biomechanics, underneath articular cartilage tissues, and pH value. This review summarizes the existing literatures on microenvironmental changes, mechanisms, and their negative effects on cartilage regeneration following cartilage and joint damage. We conclude that time-dependently rebuilding the multiple normal microenvironments of damaged cartilage is the key for cartilage regeneration after systematic studies for the timing and correlations of various microenvironment changes.

An alveolar cleft is a critical tissue defect often treated with surgery. In this research, the mimicked periosteum layer based on deposited silk fibroin membrane was fabricated for guided bone regeneration in alveolar cleft surgery. The deposited silk fibroin particle membranes were fabricated by spray-drying with different concentrations of silk fibroin (v/v): 0.5% silk fibroin (0.5% SFM), 1% silk fibroin (1% SFM), 2% silk fibroin (2% SFM), and 1% silk fibroin film (1% SFF) as the control. The membranes were then characterized and the molecular organization, structure, and morphology were observed with FT-IR, DSC, and SEM. Their physical properties, mechanical properties, swelling, and degradation were tested. The membranes were cultured with osteoblast cells and their biological performance, cell viability and proliferation, total protein, ALP activity, and calcium deposition were evaluated. The results demonstrated that the membranes showed molecular transformation of random coils to beta sheets and stable structures. The membranes had a porous layer. Furthermore, they had more stress and strain, swelling, and degradation than the film. They had more unique cell viability and proliferation, total protein, ALP activity, calcium deposition than the film. The results of the study indicated that 1% SFM is promising for guided bone regeneration for alveolar cleft surgery.

The prevalence of end-stage liver disease (ESLD) in the US is increasing at an alarming rate. It can be caused by several factors; however, one of the most common routes begins with nonalcoholic fatty liver disease (NAFLD). ESLD is diagnosed by the presence of irreversible damage to the liver. Currently, the only definitive treatment for ESLD is orthotopic liver transplantation (OLT). Nevertheless, OLT is limited due to a shortage of donor livers. Several promising alternative treatment options are under investigation. Researchers have focused on the effect of liver-enriched transcription factors (LETFs) on disease progression. Specifically, hepatocyte nuclear factor 4-alpha (HNF4α) has been reported to reset the liver transcription network and possibly play a role in the regression of fibrosis and cirrhosis. In this review, we describe the function of HNF4α, along with its regulation at various levels. In addition, we summarize the role of HNF4α in ESLD and its potential as a therapeutic target in the treatment of ESLD.

Osteopenia is common in phenylalanine hydroxylase deficient phenylketonuria (PKU). PKU is managed by limiting dietary phenylalanine. Osteopenia in PKU might reflect a therapeutic diet, with reduced bone forming materials. However, osteopenia occurs in patients who never received dietary therapy or following short-term therapy. Humans and animal studies find no correlation between bone loss, plasma hyperphenylalaninemia, bone formation, and resorption markers. Work in the Pah^enu2 mouse recently showed a mesenchymal stem cell (MSC) developmental defect in the osteoblast pathway. Specifically, Pah^enu2 MSCs are affected by energy dysregulation and oxidative stress. In PKU, MSCs oximetry and respirometry show mitochondrial respiratory-chain complex 1 deficit and over-representation of superoxide, producing reactive oxygen species affecting mitochondrial function. Similar mechanisms are involved in aging bone and other rare defects including alkaptonuria and homocysteinemia. Novel interventions to support energy and reduce oxidative stress may restore bone formation PKU patients, and in metabolic diseases with related mechanisms.