Chondrogenic Differentiation Alters the Immunosuppressive Property of Bone Marrow-Derived Mesenchymal Stem Cells, and the Effect is Partially due to the Upregulated Expression of B7 Molecules

To investigate the immunosuppressive properties of mesenchymal stem cells (MSCs), in the present study we examined the immunogenicity of undifferentiated and tri-lineage (chondrocytes, osteoblasts and adipocytes) differentiated rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic-differentiation, rat bone marrow-derived MSCs stimulated human peripheral blood monocyte-derived DCs (hDCs), leading to 8- and 4-fold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The Chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs inrosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDCs maturation causing higher CD83 expression in hDCs, whereas undifferentiated MSCs, osteogenic-and adipogenic-differentiated MSCs showed inhibitory effect on hDCs maturation. The co-stimulatory molecules B7 were up-regulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of co-cultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of DCs. The up-regulated expression of B7 molecules on the chondrogenic differentiated MSCs may be partially responsible for this event.

Scientifi c discourses on chronic pain without organic cause Incorporating gender perspective for pain resignifyng-repoliticizing

Chronic pain, without any organic or physical cause (DC), which in psycho-medical terminology is known as fi bromyalgia, (FM), is diagnosed each year to a considerable number of women in capitalistic societies. Our main interest in the following paper is to go in depth in the elaboration of this symptom, its treatment and the psychosocial effects, both in the social order as well as in the lives of the people who suffer from it. Our main goal in the following paper is to look deeper in the elaboration (conceptualization) of this symptom, its treatment and psychological affects, both in the social order as well as in the lives of the people who suffer from it, we are using linked speeches in Spanish magazines publications. The result has been the emergence of three hegemonic discourse positions: One position “scientist”, one “therapeutic of the conformity” position and one “economic and legalistic” position. Each of these has a specifi c feature, but on the whole, is enhanced, producing effects such as the absence of social context to explain the disease; disregard of gender differences in the management and treatment; the instrumentalization of pain to legitimize their practices and the subjection of women to the “psycho-biomedical” paradigm. In that way, a new signifi cance and politicization of the concept of pain is proposed.

Allogenic Peripheral Blood Derived Mesenchymal Stem Cells (MSCs) Enhance Bone Regeneration in Rabbit Ulna Critical-Sized Bone Defect Model

Mesenchymal stem cells (MSCs) were demonstrated to exist within peripheral blood (PB) of several mammalian species including human, guinea pig, mice, rat, and rabbit. Whether or not the PB derived MSCs (PBMSCs) could enhance the regeneration of large bone defects have not been reported. In this study, rabbit MSCs were obtained from mononuclear cells (MNCs) cultures of both the PB and bone marrow (BM) origin. The number of PBMSCs was relatively lower, with the colony forming efficiency (CFE) ranging from 1.2-13 per million MNCs. Under specific inductive conditions, PBMSCs differentiated into osteoblasts, chondrocytes, and adipocytes, showing multi- differentiation ability similar to BMMSCs. Bilateral 20 mm critical-sized bone defects were created in the ulnae of twelve 6-month old New Zealand white rabbits. The defects were treated with allogenic PBMSCs/Skelite (porous calcium phosphate resorbable substitute), BMMSCs/Skelite, PBMNCs/Skelite, Skelite alone and left empty for 12 weeks. Bone regeneration was evaluated by serial radiography, peripheral quantitative computed tomography (pQCT), and histological examinations. The x-ray scores and the pQCT total bone mineral density in the PBMSCs/Skelite and BMMSCs/Skelite treated groups were significantly greater than those of the PBMNCs/Skelite and Skelite alone groups (p

Osteoclastogenesis induced by sRANKL and M-CSF from the non-adherent cell population of human bone marrow is inhibited by rhBMP-2 alone or together with rhVEGF

During bone development and repair, angiogenesis, osteogenesis and bone remodelling are closely associated processes that share some common mediators. In the present study non-adherent human bone marrow mononuclear cells under the induction of sRANKL and M-CSF, differentiated into osteoclasts with TRAP positive staining, VNR expression, and Ca-P resorptive activity. The effects of various combinations of rhBMP-2 (0, 3, 30, 300 ng/ml) and rhVEGF (0, 25 ng/ml) on osteoclastogenesis potentials were examined in this experimental system. The percentages of TRAP-positive multiple nucleated cells represent osteoclast differentiation potential and the percentages of resorptive areas in the Ca-P coated plates resemble osteoclast resorption capability. The presence of rhBMP-2 at 30 and 300 ng/ml showed inhibitory effects on osteoclast differentiation and their resorptive capability in the human osteoclast culture system. rhVEGF (25 ng/ml) enhanced the resorptive function of osteoclast whenever it was used alone or combined with 3 ng/ml rhBMP-2. However, rhVEGF induced resorptive function was inhibited by 30 ng/ml and 300 ng/ml rhBMP-2 at a dose-dependent manner. Statistical analysis demonstrated that an interactive effect exists between rhBMP-2 and rhVEGF on human osteoclastogenesis. These findings suggested that an interactive regulation may exist between BMPs and VEGF signaling pathways during osteoclastogenesis, exact mechanisms are yet to be elucidated.