Abstract
The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications. Efforts have been made to control MSC behavior by using material systems to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a simple approach based on ion transporter stimulation to determine stem cell fate that avoids the use of growth factors. Addition of borax alone, transported by the NaBC1-transporter, enhanced MSC adhesion and contractility, promoted osteogenesis and inhibited adipogenesis. Stimulated-NaBC1 promoted osteogenesis via the BMP canonical pathway (comprising Smad1/YAP nucleus translocation and osteopontin expression) through a mechanism that involves simultaneous NaBC1/BMPR1A and NaBC1/α5β1/αvβ3 co-localization. We describe an original function for NaBC1 transporter, besides controlling borate homeostasis, capable of stimulating growth factor receptors and fibronectin-binding integrins. Our results open up new biomaterial engineering approaches for biomedical applications by a cost-effective strategy that avoids the use of soluble growth factors.
Highlights
The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications
With the aim of evaluating MSC osteogenic commitment, we used a combined system for simultaneous stimulation of NaBC1 and α5β1 and αvβ[3] integrins[28]
Since integrins initiate the adhesion process by generating nascent integrin-matrix linkages that afterwards develop into mature integrin-extracellular matrix (ECM) linkages, recruiting additional components under force[35], our results indicate that active NaBC1 accelerates integrin clustering to form focal adhesions (FA) in the early stages that will become mature FA in polylactic acid (PLLA)-B2% and PLLA-B5% substrates, and demonstrates that NaBC1 activation regulates cell adhesion as previously reported for other ion channels[36]
Summary
The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications. Mesenchymal stem cells (MSCs) are multipotent and capable of differentiating mesodermal lineages (reticular, adipogenic, osteogenic and chondrogenic) under certain conditions that often include growth factors[1]. Their final fate in vivo depends on a combination of physical, chemical and biological cues, all of which are present in the natural stem cell niche. Force exerted by the cells on the ECM is mediated by major adhesion receptors, integrins, mechanosensors that pull on ECM proteins and transmit mechanical forces This interaction causes cytoskeleton contraction and integrin clustering, giving rise to focal adhesions[12] and an intracellular cascade of downstream signal transduction events that determine the stem cell fate. NaBC1 and showed that the simultaneous stimulation of NaBC1 and the vascular endothelial growth factor receptor (VEGFR)
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