Organogenesis

Based on successes in preclinical animal transplant models, adoptive cell therapy (ACT) with regulatory T cells (Tregs) is a promising modality to induce allograft tolerance or reduce the use of immunosuppressive drugs to prevent rejection. Extensive work has been done in optimizing the best approach to manufacture Treg cell products for testing in transplant recipients. Collectively, clinical evaluations have demonstrated that large numbers of Tregs can be expanded ex vivo and infused safely. However, these trials have failed to induce robust drug-free tolerance and/or significantly reduce the level of immunosuppression needed to prevent solid organ transplant (SOTx) rejection...

Antibody-mediated rejection (ABMR) is the major cause of chronic allograft dysfunction and loss in kidney transplantation. The immunological mechanisms of ABMR that have been featured in the latest studies indicate a highly complex interplay between various immune and nonimmune cell types. Clinical diagnostic standards have long been criticized for being arbitrary and the lack of accuracy. Transcriptomic approaches, including microarray and RNA sequencing of allograft biopsies, enable the identification of differential gene expression and the continuous improvement of diagnostics...

Hippo pathway is a cellular regulatory pathway composed of core molecules such as MST1/2, LATS1/2, SAV1, MOB1A/B and downstream YAP/TAZ. Fully involved in regulating cell proliferation, differentiation, migration and apoptosis, the Hippo pathway is critical in regulating stem cells of oral origin, for instance, DPSCs and PDLSCs, enamel formation and periodontium regeneration. Here, we summarized the Hippo pathway involved in these progresses and concluded crosstalks of the Hippo pathway with BCL-2, ERK1/2, ROCK, TGF-β/BMP and Wnt/β-catenin pathways, hoping to provide foundation for further clinical therapy...

The human eyelid embodies a vast diversity of functions. Acting as a protective shield for the ocular apparatus and as a light regulator in the sight process, eyelids stand a fascinating - yet omitted - role in facial aesthetics, serving as a racial trait by which humankind succeeded to manifest heterogeneity as a species. These assumptions are precisely forecasted right from in-utero life through intricate processes of growth and cell differentiation. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed morphological assessments on 41 embryos and fetuses with gestational ages ranging from 6 to 29 weeks...

Mesenchymal stem cells (MSC) and induced pluripotent stem cells (iPSC) have been reported to be able to differentiate to hepatocyte in vitro with varying degree of hepatocyte maturation. A simple method to decellularize liver scaffold has been established by the Department of Histology, Faculty of Medicine, Universitas Indonesia, in SCTE IMERI lab.15 This study aims to evaluate hepatocyte differentiation from iPSCs compared to MSCs derived in our decellularized liver scaffold. The research stages started with iPSC culture, decellularization, seeding cell culture into the scaffold, and differentiation into hepatocytes for 21 days...

Encephalitis, the most significant of the central nervous system (CNS) diseases caused by Herpes simplex virus 1 (HSV-1), may have long-term sequelae in survivors treated with acyclovir, the cause of which is unclear. HSV-1 exhibits a tropism toward neurogenic niches in CNS enriched with neural precursor cells (NPCs), which play a pivotal role in neurogenesis. NPCs are susceptible to HSV-1. There is a paucity of information regarding the influence of HSV-1 on neurogenesis in humans. We investigated HSV-1 infection of NPCs from two individuals...

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...

Cardiac hypertrophy contributes to heart failure and is pathogenically modulated by a network of signaling cascades including Wnt/β-catenin signaling pathway. miRNAs have been widely demonstrated to regulate gene expression in heart development. miR-128 was routinely found as a brain-enriched gene and has been functionally associated with regulation of cardiac function. However, its role and molecular mechanisms that regulate cardiac hypertrophy remain largely unclear. Adeno-associated virus serotype 9 (AAV9)-mediated constructs with miR-128 or anti-miR-128 were generated and delivered to overexpression or blockade of miR-128 in vivo followed by HF induction with isoproterenol (ISO) or transverse aortic constriction (TAC)...

Cells with osteogenic potential are believed to be an ideal source for bone tissue bioengineering. Large bone defects require temporary substitution of the damaged parts. In this respect, the transplantation of bone cells cultured on osteogenic substrates has been investigated. To use the natural bone matrix, one approach is the so-called demineralized bone matrix (DBM). In this study, we evaluated the interaction of human fetal osteoblasts (hFOB 1.19 cells, a human fetal osteoblastic cell line) with DBM fragments...

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...

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...

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...

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...

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...

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 Pahenu2 mouse recently showed a mesenchymal stem cell (MSC) developmental defect in the osteoblast pathway...

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)...

Synergistic promotion of angiogenesis and osteogenesis in bone tissue-engineered constructs remains a crucial clinical challenge, which might be overcome by simultaneous employment of superior techniques including coculture systems, differentiation-stimulated factors, combinatorial scaffolds and bioreactors.Current study investigated the effect of flow perfusion along with coculture of human adipose stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs) on osteogenic and angiogenic differentiation...

Labial minora fusion persisting to the reproductive age is a rare type of labial fusion. Only 17 sporadic case-reports have been published to describe this disease. We report a retrospective cohort study of nine patients undergone surgical dissections in our hospital with labial minora fusion of reproductive age. General information, a medical history, gynecological examinations, preoperative ultrasonography and observations during surgery were reviewed. Four patients found vulva deformity at age 1.25 ± 1...

As a chaperone protein of progesterone receptor (PR), FK-506 Binding Protein 52 (FKBP52) can enhance the activity of PR, but the mechanism of FKBP52 affecting PR expression levels is difficult to clarify. Here, we report a novel in vitro model of ectopic endometrial stromal cells (ESCM) established through the primary culture method of endometrial stromal cells, which is used to study the details of relationship between FKBP52 abnormality and PR expression level in endometriosis (Ems). At the same time, the clinical study of the relationship between FKBP52 and PR expression levels in endometriosis patients was used to verify our conclusions...

The nail apparatus serves as a protective layer over the dorsal aspect of each distal phalanx of both hands and feet. Besides protection, other functions include serving as part of defense or attack mechanisms, scratching, and dexterity. Nail development has been a subject of interest since the 19th century, from both the phylogenetic and ontogenetic points of view. Despite the early spark of interest, nail embryology has yet been analyzed by a relatively small number of scientists. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed a morphological analysis on 41 embryos and fetuses with gestational ages that varied between 6 and 29 weeks...