Tissue Eng Part A. 2017 Jan 26. doi: 10.1089/ten.TEA.2016.0494. [Epub ahead of print]

NANOG restores contractility of MSC based senescent microtissues.

Shahini A¹, Mistriotis P², Asmani M³, Zhao R⁴, Andreadis ST⁵.

Abstract

Mesenchymal stem cells (MSC) have been extensively used in the field of tissue engineering as a source of smooth muscle cells (SMC). However, recent studies showed deficits in the contractile function of SMC derived from senescent MSC and there are no available strategies to restore the contractile function that is impaired due to cellular or organismal senescence. Here we developed a tetracycline regulatable system and employed micropost tissue arrays to evaluate the effects of the embryonic transcription factor, NANOG on the contractility of senescent MSC. Using this system we show that expression of NANOG fortified the actin cytoskeleton and restored the contractile function that was impaired in senescent MSC. NANOG increased the expression of smooth muscle α-actin (ACTA2) as well as the contractile force generated by cells in 3D microtissues. Interestingly, NANOG worked together with transforming growth factor-beta1 (TGF-β1) to further enhance the contractility of senescent microtissues. The effect of NANOG on contractile function was sustained for about ten days after termination of its expression. Our results show that NANOG could reverse the effects of stem cell senescence and restore the myogenic differentiation potential of senescent MSC. These findings may enable development of novel strategies to restore the function of senescent cardiovascular and other SMC containing tissues.