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Screening for Drugs that Enhance Wound Healing by Spurring Greater Stem Cell Activity

The enhancement of stem cell activity is a very broad theme in medical research and development. It encompasses most present stem cell therapies, treatments that largely work through their effects on native stem cell populations, the parabiosis studies in search of blood-borne factors that both influence stem cells and change with age, and research such as the open access paper here, in which more traditional drug screening is used to search for candidates that can increase stem cell activity in a specific tissue of interest:

Advances in adult tissue stem cell biology have led to the idea that pharmacological activation of resident stem cells might represent a therapeutic strategy for tissue repair. Indeed, pharmacological candidates that regulate tissue stem cells have been identified. Here, we asked whether this is a viable strategy for skin repair. Skin is a complex tissue with many endogenous tissue stem cells. These include epidermal stem cells and a population of dermal stem cells called skin-derived precursors (SKPs). Cultured SKPs can clonally reconstitute the dermis and induce hair follicle morphogenesis, suggesting key roles for the endogenous precursors in dermal maintenance and hair follicle biology.

Here, we have tested the idea that increasing the number or self-renewal of endogenous SKPs would enhance skin repair. To do so, we screened libraries of compounds that are used clinically in humans, looking for drugs that enhance SKP self-renewal. We identified two compounds, alprostadil and trimebutine maleate, that increased SKP self-renewal, likely by activating the MEK-ERK pathway. Both compounds enhanced wound healing when applied topically. These findings provide proof of principle for the idea that compounds that regulate SKPs in culture have therapeutic efficacy in vivo, and identify potential drug candidates that can be repositioned for use in humans.

Link: http://dx.doi.org/10.1016/j.stemcr.2015.12.002

Comments

A lot of people who suffer wound healing problems are doing so because they are aged. So unless you can override the signaling locally, as Reason has pointed out, stem cell treatments are on a collision course with aging.

Posted by: Jim at January 13th, 2016 3:08 PM

@Jim: this, as I've pointed out before, is one of the reason SENS Research Foundation follows and has invested in parabiosis research: to identify factors in the aging vs. youthful systemic environment that will hinder or facilitate (respectively) the implementation of cell therapy and tissue engineering as well as other rejuvenation biotechnologies. Proof-of-principle of this approach is clearly seen in the work of Conboy, Rando, Villeda, Wyss-Coray, Wagers, and others.

Equally, and particularly in persons of relatively advanced age, the restoration of the cellular and molecular integrity of aging tissues by applying each rejuvenation biotechnology will further normalize the systemic milieu, progressively making each additional therapy easier and more effective to apply, in a bootstrapping process that will accelerate as more and better rejuvenation biotechnologies come onstream.

Posted by: Michael at January 19th, 2016 2:05 PM

Stem cells combined with senolytics is one combination that has been suggested may improve stem cell engrafting Michael. I would very much like to test that given a few people in the field have talked about the idea.

Posted by: Steve h at January 19th, 2016 5:59 PM

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