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Fan X.,National Center for Biomedical Engineering Science | Nash M.E.,CSIC - Institute of Polymer Science and Technology | Barry F.P.,Regenerative Medicine Institute | Shaw G.,Regenerative Medicine Institute | And 2 more authors.
Macromolecular Rapid Communications | Year: 2015

This communication outlines the advances made in the development of thermoresponsive substrates for human mesenchymal stem cell (hMSC) expansion and subsequent controlled specific and multilineage differentiation from a previous study performed by this group. Previously, the development of an inexpensive and technically accessible method for hMSC expansion and harvesting was reported, using the solvent casting deposition method and thermoresponsive poly(N-isopropylacrylamide). Here, the logical continuation of this work is reported with the multipassage expansion of hMSCs with phenotypic maintenance followed by induced adipogenic, osteogenic, and chondrogenic differentiation. Interestingly, 1 μm thick solvent cast films are not only capable of hosting an expanding population of phenotypically preserved hMSCs similar to tissue culture plastic controls, but also the cells detached via temperature control better maintain their ability to differentiate compared to conventionally trypsinized cells. This approach to hMSC expansion and differentiation can be highly attractive to stem cell researchers where clinical therapies have seen a collective deviation away from the employment of animal derived products such as proteolytic trypsin. Here, the expansion and gentle detachment of hMSCs on/from thermoresponsive platforms is charted to include subsequent controlled specific and multilineage differentiation. The simple technique and the avoidance of animal-derived detachment products make this approach easily reproducible and desirable for possible clinical cell therapies. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Broderick B.J.,Electrical and Electronic Engineering | Broderick B.J.,National Center for Biomedical Engineering Science | Corley G.J.,Electrical and Electronic Engineering | Corley G.J.,National Center for Biomedical Engineering Science | And 7 more authors.
Journal of Applied Physiology | Year: 2010

This study investigated the hemodynamic properties of the plantar venous plexus (PVP), a peripheral venous pump in the human foot, with Doppler ultrasound. We investigated how different ways of introducing mechanical changes vary in effectiveness of displacing blood volume from the PVP. The contribution of the PVP was analyzed during both natural and device-elicited compressions. Natural compressions consisted of weight bearing on the foot and toe curl exercises. Deviceelicited compressions consisted of intermittent pneumatic compression (IPC) of the foot and electrically elicited foot muscle contractions. Ten healthy participants had their posterior tibial, peroneal, anterior tibial, and popliteal vein blood flow monitored while performing these natural and device-elicited compressions of the PVP supine and in an upright position. Results indicated that 1) natural compression of the PVP, weight bearing and toe curls, expelled a significantly larger volume of blood than device-elicited PVP compression, IPC and electrical stimulation; 2) there was no difference between the venous volume elicited by weight bearing and by toe curls; 3) expelled venous volume recorded at the popliteal vein under all test conditions was significantly greater than that recorded from the posterior tibial and peroneal veins; 4) there was no significant difference between the volume in the posterior tibial and peroneal veins; 5) ejected venous volume recorded in the upright position was significantly higher than that recorded in the supine position. Our study shows thatweight bearing and toe curls make similar contributions to venous emptying of the foot. © 2010 by the American Physiological Society. Source


Birmingham E.,Center for Biomechanics Research | Birmingham E.,National Center for Biomedical Engineering Science | Birmingham E.,Regenerative Medicine Institute REMEDI | Niebur G.L.,National Center for Biomedical Engineering Science | And 14 more authors.
European Cells and Materials | Year: 2012

Mesenchymal stem cells (MSCs) within their native environment of the stem cell niche in bone receive biochemical stimuli from surrounding cells. These stimuli likely infl uence how MSCs differentiate to become bone precursors. The ability of MSCs to undergo osteogenic differentiation is well established in vitro; however, the role of the natural cues from bone's regulatory cells, osteocytes and osteoblasts in regulating the osteogenic differentiation of MSCs in vivo are unclear. In this study we delineate the role of biochemical signalling from osteocytes and osteoblasts, using conditioned media and co-culture experiments, to understand how they direct osteogenic differentiation of MSCs. Furthermore, the synergistic relationship between osteocytes and osteoblasts is examined by transwell co-culturing of MSCs with both simultaneously. Osteogenic differentiation of MSCs was quantified by monitoring alkaline phosphatase (ALP) activity, calcium deposition and cell number. Intracellular ALP was found to peak earlier and there was greater calcium deposition when MSCs were co-cultured with osteocytes rather than osteoblasts, suggesting that osteocytes are more infl uential than osteoblasts in stimulating osteogenesis in MSCs. Osteoblasts initially stimulated an increase in the number of MSCs, but ultimately regulated MSC differentiation down the same pathway. Our novel coculture system confi rmed a synergistic relationship between osteocytes and osteoblasts in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This study provides important insights into the mechanisms at work within the native stem cell niche to stimulate osteogenic differentiation and outlines a possible role for the use of co-culture or conditioned media methodologies for tissue engineering applications. Source

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