A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) treatment is stem cell therapy. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). However, the mechanisms responsible for the beneficial effect are not fully understood. The aim here was to investigate the mechanism by studying the effect of intraspinally injected NP-iPS into asymptomatic and early symptomatic superoxide dismutase (SOD)1G93A transgenic rats. Prior to transplantation, NP-iPS were characterized in vitro for their ability to differentiate into a neuronal phenotype. Motor functions were tested in all animals, and the tissue was analyzed by immunohistochemistry, qPCR, and Western blot. NP-iPS transplantation significantly preserved MNs, slowed disease progression, and extended the survival of all treated animals. The dysregulation of spinal chondroitin sulfate proteoglycans was observed in SOD1G93A rats at the terminal stage. NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs. In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not differentiate. The findings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs).

• MeSH
• Amyotrophic Lateral Sclerosis therapy   MeSH
• Induced Pluripotent Stem Cells cytology   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Neural Stem Cells cytology   metabolism   transplantation   MeSH
• Neuronal Plasticity * MeSH
• Nerve Growth Factors genetics   metabolism   MeSH
• Peripheral Nerves physiology   MeSH
• Rats, Sprague-Dawley MeSH
• Apoptosis Regulatory Proteins genetics   metabolism   MeSH
• Nerve Regeneration MeSH
• Tenascin genetics   metabolism   MeSH
• Stem Cell Transplantation methods   MeSH
• Versicans genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

In the mammalian ovary, the hyaluronan (HA)-rich cumulus extracellular matrix (ECM) organized during the gonadotropin-induced process of oocyte maturation is essential for ovulation of the oocyte-cumulus complex (OCC) and fertilization. Versican is an HA-binding proteoglycan that regulates cell function and ECM assembly. Versican cleavage and function remain to be determined in ovarian follicle. We investigated versican expression in porcine ovarian follicles by real-time (RT)-PCR and western blotting. The aims of the present work were to determine whether 1) versican was produced and cleaved by porcine OCCs during gonadotropin stimulation; 2) these processes were autonomous or required the participation of mural granulosa cells (MGCs); and 3) versican cleavage was involved in the formation or degradation of expanded cumulus ECM. We demonstrate two cleavage products of G1 domain of versican (V1) accumulated in the HA-rich cumulus ECM. One of them, a G1-DPEAAE N-terminal fragment (VG1) of ~70 kDa, was generated from V1 during organization of HA in in vivo and in vitro expanded porcine OCCs. Second, the V1-cleaved DPEAAE-positive form of ~65 kDa was the only species detected in MGCs. No versican cleavage products were detected in OCCs cultured without follicular fluid. In summary, porcine OCCs are autonomous in producing and cleaving V1; the cleaved fragment of ~70 kDa VG1 is specific for formation of the expanded cumulus HA-rich ECM.

• MeSH
• Cell Differentiation MeSH
• Epitopes immunology   MeSH
• Cells, Cultured MeSH
• Oocytes cytology   immunology   metabolism   MeSH
• Swine MeSH
• Versicans genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Chemokine CCL2 antagonists & inhibitors   MeSH
• Carcinoma, Transitional Cell * immunology   physiopathology   pathology   MeSH
• Humans MeSH
• Neoplasm Metastasis immunology   physiopathology   pathology   MeSH
• Urinary Bladder Neoplasms * immunology   physiopathology   pathology   MeSH
• Versicans biosynthesis   genetics   adverse effects   MeSH
• Check Tag
• Humans MeSH

Focal cortical dysplasias (FCDs) of the brain are recognized as a frequent cause of intractable epilepsy. To contribute to the current understanding of the mechanisms of epileptogenesis in FCD, our study provides evidence that not only cellular alterations and synaptic transmission, but also changed diffusion properties of the extracellular space (ECS), induced by modified extracellular matrix (ECM) composition and astrogliosis, might be involved in the generation or spread of seizures in FCD. The composition of the ECM in FCD and non-malformed cortex (in 163 samples from 62 patients) was analyzed immunohistochemically and correlated with the corresponding ECS diffusion parameter values determined with the real-time iontophoretic method in freshly resected cortex (i.e. the ECS volume fraction and the geometrical factor tortuosity, describing the hindrances to diffusion in the ECS). The ECS in FCD was shown to differ from that in non-malformed cortex, mainly by the increased accumulation of certain ECM molecules (tenascin R, tenascin C, and versican) or by their reduced expression (brevican), and by the presence of an increased number of astrocytic processes. The consequent increase of ECS diffusion barriers observed in both FCD type I and II (and, at the same time, the enlargement of the ECS volume in FCD type II) may alter the diffusion of neuroactive substances through the ECS, which mediates one of the important modes of intercellular communication in the brain - extrasynaptic volume transmission. Thus, the changed ECM composition and altered ECS diffusion properties might represent additional factors contributing to epileptogenicity in FCD.

• MeSH
• Astrocytes metabolism   MeSH
• Brevican analysis   MeSH
• Diffusion MeSH
• Child MeSH
• Adult MeSH
• Extracellular Matrix chemistry   metabolism   MeSH
• Extracellular Space chemistry   metabolism   MeSH
• Iontophoresis methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Malformations of Cortical Development metabolism   pathology   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Brain Diseases metabolism   pathology   MeSH
• Neocortex pathology   MeSH
• Child, Preschool MeSH
• Tenascin analysis   MeSH
• Versicans analysis   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Collagen triple helix repeat containing 1 (CTHRC1) affects Wnt signalling, collagen deposition and bone formation. It is an extracellular matrix protein which is also abnormally expressed in the tumour microenvironment. CTHRC1 has not been studied in breast cancer by immunohistochemistry. AIMS: To examine expression of CTHRC1 together with periostin and versican in breast cancer patients and investigate its association with clinicopathological characteristics. METHODS: The formalin-fixed paraffin-embedded tissues of 173 invasive carcinomas (classified into WHO histotypes and luminal, triple negative and Her2 subtypes), as well as normal tissues, precursor lesions and metastatic lymph nodes were stained by relevant antibodies, assessed semiquantitatively by histoscore and statistically evaluated. RESULTS: Expression of CTHRC1, versican and periostin was significantly higher in breast cancer than in normal tissue or precursor lesions. CTHRC1 stromal expression was enhanced in triple negative cases and also in patients with bone metastasis. Periostin expression was high in primary tumours, in particular triple negative ones, and also in their lymph node metastases. Cox regression analysis showed that in patients with high periostin, the risk of bone metastases increased with increased CTHRC1 expression. CONCLUSIONS: CTHRC1 and periostin play important roles in breast cancer progression. These preliminary results show that combined evaluation of CTHRC1 and periostin could serve as a potential marker for breast cancer bone metastasis; the other observations contribute to the description of the tumour microenvironment, with implications for lymph node and bone metastasis.

• MeSH
• Adult MeSH
• Extracellular Matrix Proteins metabolism   MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Cell Adhesion Molecules metabolism   MeSH
• Biomarkers, Tumor metabolism   MeSH
• Bone Neoplasms metabolism   secondary   MeSH
• Breast Neoplasms metabolism   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Versicans metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

ACI is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. The method is based on in vitro chondrocyte cultivation. Two different culture conditions, rotating- wall-vessel bioreactor and static culture, were assessed by their effect on the re-differentiation potential of human articular chondrocytes seeded into a hydrogel scaffold. Gene expression analysis of the tissue-engineered construct revealed no significant difference between the tested systems.

• MeSH
• Aggrecans metabolism   MeSH
• Bioreactors MeSH
• Cell Differentiation genetics   MeSH
• Cell Culture Techniques MeSH
• Chondrocytes cytology   metabolism   transplantation   MeSH
• Gene Expression MeSH
• Cartilage, Articular cytology   metabolism   MeSH
• Collagen Type II metabolism   MeSH
• Collagen Type I metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Hydrogel, Polyethylene Glycol Dimethacrylate MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds MeSH
• Versicans metabolism   MeSH
• Check Tag
• Humans MeSH