The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review.

Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.

Differentiation of Human Mesenchymal Stem Cells from Wharton's Jelly Towards Neural Stem Cells Using A Feasible and Repeatable Protocol.

The transplantation of neural stem cells (NSCs) capable of regenerating to the cells of the central nervous system (CNS) is a promising strategy in the treatment of CNS diseases and injury. As previous studies have highlighted mesenchymal stem cells (MSCs) as a source of NSCs, this study aimed to develop a feasible, efficient, and reproducible method for the neural induction of MSCs isolated from Wharton's jelly (hWJ-MSCs). We induced neural differentiation in a monolayer culture using epidermal growth factor, basic fibroblast growth factor, N2, and B27 supplements. This resulted in a homogenous population of proliferating cells that expressed certain neural markers at both the protein and mRNA levels. Flow cytometry and immunocytochemistry confirmed the expression of neural markers: nestin, sex-determining region Y (SRY) box 1 and 2 (SOX1 and SOX2), microtubule-associated protein 2 (MAP2), and glial fibrillary acidic protein (GFAP). The qRT-PCR analysis revealed significantly enhanced expression of nestin and MAP2 in differentiated cells. This study confirms that it is possible to generate NSCs-like cells from hWJ-MSCs in a 2D culture using a practical method. However, the therapeutic effectiveness of such differentiated cells should be extended to confirm the terminal differentiation ability and electrophysiological properties of neurons derived from them.

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration.

INTRODUCTION: Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic in-nervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). MATERIALS AND METHODS: Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DbH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the inves-tigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. RESULTS: The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympa-thetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 µg/kg b.w./day, the percentages of SP+/DbH+ and CGRP+/DbH+ nerve fibers were similar to the control. However at a ten times higher dose, BPA caused an increased number of SP+/ DbH+ and CGRP+/ DbH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. CONCLUSIONS: BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were excep-tionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic pa-renchymal cells.

Application of MRI for the Diagnosis of Neoplasms.

AIM: The aim of the study was to determine the most commonly diagnosed neoplasms in the MRI scanned patient population and indicate correlations based on the descriptive variables. METHODS: The SPSS software was used to determine the incidence of neoplasms within the specific diagnoses based on the descriptive variables of the studied population. Over a five year period, 791 patients and 839 MRI scans were identified in neoplasm category (C00-D48 according to the International Statistical Classification of Diseases and Related Health Problems ICD-10). RESULTS: More women (56%) than men (44%) represented C00-D48. Three categories of neoplasms were recorded. Furthermore, benign neoplasms were the most numerous, diagnosed mainly in patients in the fifth decade of life, and included benign neoplasms of the brain and other parts of the central nervous system. CONCLUSIONS: Males ≤ 30 years of age with neoplasms had three times higher MRI scans rate than females of the same age group; even though females had much higher scans rate in every other category. The young males are more often selected for these scans if a neoplasm is suspected. Finally, the number of MRI-diagnosed neoplasms showed a linear annual increase.

Zinc Transporter 3 (Znt3) as an Active Substance in the Enteric Nervous System of the Porcine Esophagus.

Zinc transporter 3 (ZnT3), a member of the SLC 30 zinc transporter family, is involved in the transport of zinc ions from the cytoplasm into synaptic vesicles or intracellular organelles. The aim of the present study was to investigate for the first time the percentage of ZnT3-like immunoreactive (ZnT3-LI) neurons in the enteric nervous system (ENS) of the porcine esophagus and denotation of their neurochemical coding. Routine double- and triple-immunofluorescence labeling of cervical, thoracic, and abdominal fragments of esophagus for ZnT3 with protein gene product (PGP 9.5; used as pan-neuronal marker), nitric oxide synthase (NOS), somatostatin, vasoactive intestinal peptide (VIP), vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), and galanin (GAL) was performed. The percentage of ZnT3-LI neurons in myenteric ganglia amounted to 50.2 ± 4.7, 63.4 ± 8.3, and 77.1 ± 1.1 % of all PGP 9.5-like immunoreactive neuronal cells in cervical, thoracic, and abdominal esophagus, respectively. In submucous ganglia, these values in particular parts of esophagus amounted to 46.3 ± 6.3, 81.0 ± 8.1, and 74.4 ± 4.4 %. Znt3 co-localized mainly with VAChT, NPY, GAL, NOS, and VIP, but the degree of co-localization depended on the "kind" of enteric ganglia and part of esophagus studied. The obtained results suggest that both ZnT3 and zinc ions may play important and various roles in the neuronal regulation of esophageal functions.