Bone marrow-derived mesenchymal stem cells become anti-angiogenic when chondrogenically or osteogenically differentiated:implications for bone and cartilage tissue engineering

Osteochondral tissue repair requires formation of vascularized bone and avascular cartilage. Mesenchymal stem cells stimulate angiogenesis both in vitro and in vivo but it is not known if these proangiogenic properties change as a result of chondrogenic or osteogenic differentiation. We investigated the angiogenic/antiangiogenic properties of equine bone marrow-derived mesenchymal stem cells (eBMSCs) before and after differentiation in vitro. Conditioned media from chondrogenic and osteogenic cell pellets and undifferentiated cells was applied to endothelial tube formation assays using Matrigel™. Additionally, the cell secretome was analysed using LC-MS/MS mass spectrometry and screened for angiogenesis and neurogenesis-related factors using protein arrays. Endothelial tube-like formation was supported by conditioned media from undifferentiated eBMSCs. Conversely, chondrogenic and osteogenic conditioned media was antiangiogenic as shown by significantly decreased length of endothelial tube-like structures and degree of branching compared to controls. Undifferentiated cells produced higher levels of angiogenesis-related proteins compared to chondrogenic and osteogenic pellets. In summary, eBMSCs produce an array of angiogenesis-related proteins and support angiogenesis in vitro via a paracrine mechanism. However, when these cells are differentiated chondrogenically or osteogenically, they produce a soluble factor(s) that inhibits angiogenesis. With respect to osteochondral tissue engineering, this may be beneficial for avascular articular cartilage formation but unfavourable for bone formation where a vascularized tissue is desired. © Copyright 2014, Mary Ann Liebert, Inc.

Whole body vibration treatments in postmenopausal women can improve bone mineral density:results of a stimulus focussed meta-analysis

Whole body vibration treatment is a non-pharmacological intervention intended to stimulate muscular response and increase bone mineral density, particularly for postmenopausal women. The literature related to this topic is controversial, heterogeneous, and unclear despite the prospect of a major clinical effect. The aim of this study was to identify and systematically review the literature to assess the effect of whole body vibration treatments on bone mineral density (BMD) in postmenopausal women with a specific focus on the experimental factors that influence the stimulus. Nine studies fulfilled the inclusion criteria, including 527 postmenopausal women and different vibration delivery designs. Cumulative dose, amplitudes and frequency of treatments as well as subject posture during treatment vary widely among studies. Some of the studies included an associated exercise training regime. Both randomized and controlled clinical trials were included. Whole body vibration was shown to produce significant BMD improvements on the hip and spine when compared to no intervention. Conversely, treatment associated with exercise training resulted in negligible outcomes when compared to exercise training or to placebo. Moreover, side-alternating platforms were more effective in improving BMD values than synchronous platforms and mechanical oscillations of magnitude higher than 3 g and/or frequency lower than 25 Hz were also found to be effective. Treatments with a cumulative dose over 1000 minutes in the follow-up period were correlated to positive outcomes. Our conclusion is that whole body vibration treatments in elderly women can reduce BMD decline.However, many factors (e.g. amplitude, frequency and subject posture) affect the capacity of the vibrations to propagate to the target site; the adequate level of stimulation required to produce these effects has not yet been defined. Further biomechanical analyses to predict the propagation of the vibration waves along the body and assess the stimulation levels are required.