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Regenerative medicine approaches to cartilage tissue repair have mainly been concerned with the implantation of a scaffold material containing monolayer expanded cells into the defect, with the aim to differentiate the cells into chondrocytes. While this may be a valid approach, the secretome of the implanted cells and its effects on the endogenous resident cells, is gaining in interest. This review aims to summarize the knowledge on the secretome of mesenchymal stem cells, including knowledge from other tissues, in order to indicate how these mechanisms may be of value in repairing articular cartilage defects. Potential therapies and their effects on the repair of articular cartilage defects will be discussed, with a focus on the transition from classical cell therapy to the implantation of cell free matrices releasing specific cytokines.

Background aims The diverse phenotypic changes and clinical and economic disadvantages associated with the monolayer expansion of bone marrow–derived mesenchymal stromal cells (MSCs) have focused attention on the development of one-step intraoperative cells therapies and homing strategies. The mononuclear cell fraction of bone marrow, inclusive of discrete stem cell populations, is not well characterized, and we currently lack suitable cell culture systems in which to culture and investigate the behavior of these cells. Methods Human bone marrow–derived mononuclear cells were cultured within fibrin for 2 weeks with or without fibroblast growth factor-2 supplementation. DNA content and cell viability of enzymatically retrieved cells were determined at days 7 and 14. Cell surface marker profiling and cell cycle analysis were performed by means of multi-color flow cytometry and a 5-ethynyl-2′-deoxyuridine incorporation assay, respectively. Results Total mononuclear cell fractions, isolated from whole human bone marrow, was successfully cultured in fibrin gels for up to 14 days under static conditions. Discrete niche cell populations including MSCs, pericytes and hematopoietic stem cells were maintained in relative quiescence for 7 days in proportions similar to that in freshly isolated cells. Colony-forming unit efficiency of enzymatically retrieved MSCs was significantly higher at day 14 compared to day 0; and in accordance with previously published works, it was fibroblast growth factor-2–dependant. Conclusions Fibrin gels provide a simple, novel system in which to culture and study the complete fraction of bone marrow–derived mononuclear cells and may support the development of improved bone marrow cell–based therapies.

Mesenchymal stem cells are universally regarded across many fields of medicine, as one of the most promising cell types for use in cell-based therapies. Although not yet fully understood, the therapeutic effects of these cells are largely attributed to the trophic actions of growth factors and cytokines present in the cell secretome. Specifically, the angiogenic and neurogenic properties of these cells make them attractive for the repair of vascularised and innervated tissues. In this study, we investigate the effect of mesenchymal stem cell conditioned media on in vitro assays of angiogenesis and nerve growth. We describe the use of two state of the art high content and high throughput cell analysis systems and compare them against manual analysis techniques. Mesenchymal stem cell secretomes stimulated angiogenesis and nerve growth in vitro in a donor dependant manner. Levels of neuroregulin, platelet-derived growth factor-AA and glial-derived neurotrophic factor, positively correlated with the observed angiogenic effects of these cells. High content and high throughput cell analysis systems such as the ones used in this study, may provide rapid screening tools to assist not only with patient selection but the identification of predictive therapeutic markers to support clinical outcome monitoring for patients treated with stem cell therapies.

Background context Transplantation of bone marrow cells into spinal cord lesions promotes functional recovery in animal models, and recent clinical trials suggest possible recovery also in humans. The mechanisms responsible for these improvements are still unclear. Purpose To characterize spinal cord motor neurite interactions with human bone marrow stromal cells (MSCs) in an in vitro model of spinal cord injury (SCI). Study design/setting Previously, we have reported that human MSCs promote the growth of extending sensory neurites from dorsal root ganglia (DRG), in the presence of some of the molecules present in the glial scar, which are attributed with inhibiting axonal regeneration after SCI. We have adapted and optimized this system replacing the DRG with a spinal cord culture to produce a central nervous system (CNS) model, which is more relevant to the SCI situation. Methods We have developed and characterized a novel spinal cord culture system. Human MSCs were cocultured with spinal motor neurites in substrate choice assays containing glial scar-associated inhibitors of nerve growth. In separate experiments, MSC-conditioned media were analyzed and added to spinal motor neurites in substrate choice assays. Results As has been reported previously with DRG, substrate-bound neurocan and Nogo-A repelled spinal neuronal adhesion and neurite outgrowth, but these inhibitory effects were abrogated in MSC/spinal cord cocultures. However, unlike DRG, spinal neuronal bodies and neurites showed no inhibition to substrates of myelin-associated glycoprotein. In addition, the MSC secretome contained numerous neurotrophic factors that stimulated spinal neurite outgrowth, but these were not sufficient stimuli to promote spinal neurite extension over inhibitory concentrations of neurocan or Nogo-A. Conclusions These findings provide novel insight into how MSC transplantation may promote regeneration and functional recovery in animal models of SCI and in the clinic, especially in the chronic situation in which glial scars (and associated neural inhibitors) are well established. In addition, we have confirmed that this CNS model predominantly comprises motor neurons via immunocytochemical characterization. We hope that this model may be used in future research to test various other potential interventions for spinal injury or disease states. © 2014 Elsevier Inc. All rights reserved.

Resume Le cancer de la prostate est en frequence le deuxieme cancer chez l’homme. Souvent, initialement hormono-dependant, la perte de reponse aux traitements anti-androgeniques survient au cours de la progression tumorale, traduisant l’emergence d’un phenotype hormono-independant. Afin d’etudier les bases morphologiques, genetiques et moleculaires associees a la perte d’hormono-dependance, nous avons etabli un modele de xenogreffe d’adenocarcinome prostatique humain, PAC120, avec ses deux variants : hormono-dependant (HD) et hormono-independant (HID). La croissance de PAC120 HD peut etre inhibee par castration chirurgicale ou par administration d’un antagoniste de la LHRH, le FE200486 (Ferring, San Diego, CA). L’evolution vers l’hormono-independance est associee a une differenciation mucoide ou neuroendocrine, a la survenue d’alterations chromosomiques supplementaires et a des variations d’expression de genes. PAC120 est un nouveau modele de cancer de prostate qui offre l’opportunite d’etudier les mecanismes d’echappement hormonal et d’evaluer l’efficacite de nouveaux agents therapeutiques.

The results of X-ray diffraction, magnetic susceptibility and Mossbauer investigations of RFe 10 Cr 2 intermetallic compounds (R=Y, Nd, Gd, Tb, Dy, Ho, Er and Tm) are presented and discussed. The variation with a sample composition of the lattice constants, unit cell volume, Curie temperature, iron and rare earth magnetic moments, magnetic anisotropy field and 57 Fe hyperfine interaction parameters are shown. The Curie temperatures of the RFe 10 Cr 2 series follow the same trend as in other R-Fe compounds and range from 466 K (for TmFe 10 Cr 2 ) to 585 K (for GdFe 10 Cr 2 ). Spin reorientation transition phenomena caused by the competition between the rare earth and iron sublattice magnetic anisotropies are observed for R=Tb, Dy and Er. The sample composition has little influence on the 57 Fe hyperfine interaction parameters. The numerical analysis of Mossbauer spectra shows that chromium atoms have a pronounced preference for occupying 8i sublattice in the whole series of the investigated compounds. From the magnetic susceptibility and Mossbauer data the approximate values of iron and rare earth magnetic moments are derived.

Hyperfine fields have been studied at liquid nitrogen temperature in Cd x Cu 1− x Fe 2 O 4 (0 ⩽ x ⩽ 0.5) ferrites by Mossbauer and NMR spectroscopies. The distributions of the hyperfine fields at iron sites, caused by substitution of cadmium for copper, are observed both in the tetrahedral and octahedral crystal sublattices. In both sublattices the values of the averaged hyperfine field decrease with increasing cadmium concentration. The hyperfine field distributions and size reductions are more pronounced in the octahedral sublattice than in the tetrahedral one. They are explained by different statistical distributions of the metallic cations within the tetrahedral and octahedral crystal sublattices. The Mossbauer effect and NMR data are in a good agreement each with other.

The influence of samarium on the magnetic and electron transport properties of amorphous SmxFe80−xB20, 0 ⩽ × ⩽ 6, was investigated by Mossbauer spectroscopy and by electrical resistivity and magnetoresistance measurements. The resistivity of the alloys increases by about 5% in the temperature range from 78 to 290 K. For Sm6Fe74B20 ribbons a positive contribution to the magnetoresistance was found. The averaged value of the 57Fe hyperfine magnetic field decreases slightly with increasing samarium content. Variations in the line intensities of Mossbauer spectra recorded for ribbons at 78 K indicate a rotation of magnetization towards the normal to the ribbon via positive magnetostriction.

The RFe 2 Si 2 and RFe 2 Ge 2 intermetallic compounds, where R denotes a rare earth element, were investigated by X-ray diffraction and Mossbauer spectroscopy. The two series behave similarly in many respects. The values of lattice constants, isomer shift and quadrupole splitting vary gradually across the range of rare earths. Small deviations of the lattice constants of YbFe 2 Si 2 and CeFe 2 Si 2 compounds from the overall trend of the lattice parameters may indicate a non-trivalent state of ytterbium and cerium ions. The quadrupole splitting observed for both series reflects a deviation from the ideal tetrahedral coordination of iron-site neighbours.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

1. 1. Two major glycoprotein components were released in vitro by rat gastric mucosal cells after 4 hr incubation with radioisotopes: a high molecular weight fraction with the characteristics of a fucomucin and a low molecular weight fraction, the latter having a higher specific radioactivity than the former. 2. 2. Pulse chase experiments indicate that several low and high molecular weight glycoproteins are synthesized simultaneously with no precursor-product relationship between them. 3. 3. Common antigenic determinants, specific to the stomach were found on the 2 fractions, using immunofluorescence, both fractions appeared to be present in the same cells.

The influence of the Rayleigh and Compton contributions to a Mossbauer scattering line is studied. A Mossbauer scattering spectrum of absorption character is theoretically predicted and experimentally observed for iron impurities in beryllium.

Immunofluorescence studies showed that human gastric M 1 antigens and intestinal M 3 antigen are associated respectively with the mucus cells of surface gastric epithelium and with the intestinal goblet cells of the normal adult gastrointestinal tract. In the fetus and new born, it was possible to demonstrate by use of double labeling (fluorescein and rhodamine) that some goblet cells of colonic glands contain both the M 1 and M 3 antigens. This ‘fetal-type’ association of M antigens, which could not be found in the normal adult colonic mucosa, was observed in some goblet cells of the transitional mucosa adjacent to human colonic adenocarcinomas. Probably it represents the reappearance of a fetal-type pattern associated with the tumors.

Forty-one benign and malignant ovarian tumors and 12 normal ovaries were studied immunologically, with extracts of gastric mucosa as reference, in the presence of antimucosa antisera, adult gastric antipepsinogens (anti Pg I–II, anti Pg III and anti Pg IV) and fetal gastric antipepsinogens (anti Pg IV). Pepsinogens were identified in 7 out of 24 benign tumors, all of the mucinous type and in 1 out of 17 malign tumors. Pepsinogen secretion did not occur in normal ovaries. The potentiality of pepsinogen synthesis by tumoral ovaries was the same as that of other antigens of the gastric or intestinal type as recently found in the same tumors. This potentiality did not seem to be linked to the malignancy of the tumors studied.