Research Article: hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding

Date Published: May 23, 2013

Publisher: Impact Journals LLC

Author(s): Hanadie Yousef, Michael J. Conboy, Ju Li, Matthew Zeiderman, Tandis Vazin, Christina Schlesinger, David V. Schaffer, Irina M. Conboy.

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Abstract

This work builds upon our findings that proteins secreted by hESCs exhibit pro-regenerative activity, and determines that hESC-conditioned medium robustly enhances the proliferation of both muscle and neural progenitor cells. Importantly, this work establishes that it is the proteins that bind heparin which are responsible for the pro-myogenic effects of hESC-conditioned medium, and indicates that this strategy is suitable for enriching the potentially therapeutic factors. Additionally, this work shows that hESC-secreted proteins act independently of the mitogen FGF-2, and suggests that FGF-2 is unlikely to be a pro-aging molecule in the physiological decline of old muscle repair. Moreover, hESC-secreted factors improve the viability of human cortical neurons in an Alzheimer’s disease (AD) model, suggesting that these factors can enhance the maintenance and regeneration of multiple tissues in the aging body.

Partial Text

Tissue regeneration and maintenance dramatically and invariably decline with age, eventually causing failure of multiple organ systems in all mammals. In muscle, the loss of tissue regeneration with age is thought to be imposed by signaling changes in the satellite stem cell niche, and interestingly, the aging of stem cell niches is to some extent similar between muscle, brain, blood, and other tissues [1-3]. Our previous work found that human embryonic stem cells (hESCs) produce soluble secreted molecules that can counteract the age-imposed inhibition of muscle regeneration, an “anti-aging” activity that is lost when the hESCs differentiate [4, 5].

 

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