Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects - A preclinical study.

For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects. TBM, and MSCs committed or not, and cultured in two- or three-dimensions were mixed with BCP and implanted in bilateral parietal bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant de novo bone formation was observed in rhBMP-2 and BG groups, and in a lesser amount, when BCP biomaterials were mixed with TBM or committed MSCs cultured in three-dimensions. Due to the efficacy and safety of the TBM/BCP combination approach, we recommend this one-step procedure for further clinical investigation. STATEMENT OF SIGNIFICANCE: For craniofacial repair, total bone marrow (BM) and BM mesenchymal stem cell (MSC)-based regenerative medicine have shown to be promising in alternative to bone grafting (BG). Therefore, clinicians might be unsure as to which approach will offer the most benefit. Here, BM and MSCs committed or not were mixed with calcium phosphate ceramics (CaP) and implanted in bone defects in rats. RhBMP-2 and BG were used as positive controls. After 7 weeks, significant bone formation was observed in rhBMP-2 and BG groups, and when CaP were mixed with BM or committed MSCs. Since the BM-based procedure does not require bone harvest or cell culture, but provides de novo bone formation, we recommend consideration of this strategy for craniofacial applications.

Health claims assessment in the field of joint and cartilage: a consensus viewpoint of the Group for the Respect of Ethics and Excellence in Science.

INTRODUCTION: In 2006, the European Parliament and Council issued a regulation (No. 1924/2006) for the nutrition and health claims made on foods, including food supplements. According to the regulation, the use of nutrition and health claims shall only be permitted if the substance in respect of which the claim is made has been shown to have a beneficial nutritional or physiological effect. In the field of joint and cartilage health, there is no clear scientific-based definition of the nature of such a beneficial nutritional or physiological effect. The objective of this paper is to scientifically define the possible content of health claims related to joint and cartilage health and to provide scientific guidelines for the design of clinical studies which need to be adopted to substantiate such health claims. METHODS: Literature review up to September 2011 followed by a consensus expert discussion organized by the Group for the Respect of Ethics and Excellence in Science (GREES). RESULTS: In line with the general principles of the PASSCLAIM and the Codex recommendations, the GREES identified four acceptable health claims related to joint and cartilage health based on the effects on discomfort, joint and cartilage structural integrity or risk factors for joint and cartilage diseases. The GREES considers that randomized controlled trials on a relevant outcome is the best design to assess health claims. Moreover, animal studies could also be of interest to substantiate some health claims, to assess the clinical relevance of endpoints used in human studies or to extrapolate data obtained in patients to the target (apparently) healthy population. CONCLUSION: According to the methodology and biomarkers used in the study and whether or not additional animal studies are provided to support the claim, various health claims can be acceptable in the field of joint and cartilage health.

Cartilage tissue engineering: From hydrogel to mesenchymal stem cells.

Articular cartilage does not repair itself spontaneously. To promote its repair, the transfer of stem cells from adipose tissue (ATSC) using an injectable self-setting cellulosic-hydrogel (Si-HPMC) appears promising. In this context, the objective of this work was to investigate the influence of in vitro chondrogenic differentiation of ATSC on the in vivo cartilage formation when combined with Si-HPMC. In a first set of experiments, we characterized ATSC for their ability to proliferate, self renew and express typical mesenchymal stem cell surface markers. Then, the potential of ATSC to differentiate towards the chondrogenic lineage and the optimal culture conditions to drive this differentiation were evaluated. Real-time RT-PCR and histological analysis for sulphated glycosaminoglycans and type II collagen revealed that 3-dimensional culture and hypoxic condition favored ATSC chondrogenesis regarding mRNA expression level and the corresponding proteins production. In order to assess the phenotypic stability of chondrogenically-differentiated ATSC, real-time RT-PCR for specific terminal chondrogenic markers and alkaline phosphatase activity assay were performed. In addition to promote chondrogenesis, our culture conditions seem to prevent the terminal differentiation of ATSC. Histological examination of ATSC/Si-HPMC implants suggested that the in vitro chondrogenic pre-commitment of ATSC in monolayer is sufficient to obtain cartilaginous tissue in vivo.

An injectable cellulose-based hydrogel for the transfer of autologous nasal chondrocytes in articular cartilage defects.

Articular cartilage has a low capacity for spontaneous repair. To promote the repair of this tissue, the transfer of autologous chondrocytes using a three-dimensional matrix appears promising. In this context, the aim of the present work was to investigate the potential use of autologous rabbit nasal chondrocytes (RNC) associated with an injectable self-setting cellulose-based hydrogel (Si-HPMC). Firstly, the influence of Si-HPMC on chondrocytic phenotype was investigated by real-time PCR for specific chondrocyte markers (type II collagen and aggrecan) and type I collagen. Thereafter, autologous RNC were amplified in vitro for 4 weeks before transplantation with Si-HPMC into a rabbit articular cartilage defect followed by analysis 6 weeks later. Implants were histologically characterized for the presence of sulfated GAG and type II collagen. Transcripts analysis indicated that dedifferentiated RNC recovered expression of the main chondrocytic markers after in vitro three-dimensional culture within Si-HPMC. Histological analysis of autologous RNC transplanted in an articular cartilage defect revealed the formation of repair tissue with a histological organization similar to that of healthy articular cartilage. In addition, immunohistological analysis of type II collagen suggested that the repair tissue was a hyaline-like cartilage. Si-HPMC hydrogel associated with nasal chondrocytes therefore appears a promising injectable tissue engineering device for the repair of articular cartilage.