Youthful Healing, Old Bodies: A Surprising Journey into Biotechnology
Understanding the biological process of aging is essential to improving it. Stanford researchers and Faculty Affiliates Professor Helen Blau (who leads the Baxter Laboratory for Stem Cell Biology), and Professor of Mechanical Engineering Juan Santiago (who leads the Stanford Microfluidics Laboratory), as well as PhD candidate John Ramunas, each aim to improve this understanding through their combined expertise. The story of their ongoing research project, seed funded by the Center on Longevity, exemplifies the organic evolution of research itself and the unexpected value of interdisciplinary collaboration.
THE STORY OF A PROJECT
The story begins with understanding how we heal. As we age, our healing process deteriorates until it is slow and incomplete in comparison with our younger selves. This gradual decline is linked to the deterioration of the rest of our system with age, and understanding how to slow — or even halt — its advance could have promising implications for longevity research.
When it comes to the nature of the healing process, there are some key elements that we already know: There are certain molecules crucially involved in healing (though to what extent remains uncertain), and the presence of these molecules diminishes with age. It is also known that the timing of the molecules’ delivery to an injured area is pivotal to successful recovery. Thus timing, as well as quantity, can impact the ultimate success of the healing process.
Is it possible that our deteriorating healing process is caused by the diminishing presence of these molecules in our system? Might there be a way of artificially mimicking the natural delivery of a younger organism, to achieve the same youthful healing process? These are the questions of aging, healing, and longevity that Blau, Santiago, and Ramunas sought to address: By creating a mechanism that would successfully deliver the crucial molecules to injured and old animals (in this case, the ubiquitous and much-studied lab mouse), the research team sought to pinpoint the biological underpinnings of rejuvenation.
PRACTICAL CHALLENGES
In the natural healing process of a young animal, the molecules involved are delivered at specific times, and in specific quantities. In order to successfully mimic the natural delivery, the artificial mechanism needed to be similarly exact. This was the first of a range of challenges:
First, a precise and reliable delivery method necessitated a pump mechanism, propelling the molecules into the system. Second, the lab mice, being both live and lively, needed to carry the pump with them as they went about their daily lives, requiring the pump to be small and portable. Third, the mechanism needed to be remotely controlled, as timing was of the essence.
These criteria resulted in the project’s first attempt at a pump, designed to be held in place by a “mouse backpack.” From this early stage, the project depended on the combined expertise of the three researchers — Blau brought a body of research in the healing responses of mice to injury, Santiago his expertise in mechanical engineering, and Ramunas his interdisciplinary experience which allowed him to support and intertwine both fields. It was at this point that the team approached the Center on Longevity, which in turn supported the innovative and multidisciplinary effort with seed funding.
Unfortunately, a significant challenge sprang up right away. It turned out that mice are not only very small creatures, but incredibly agile ones. Despite a range of designs, the mice could not be induced to keep their packs in place.
“Mice can squeeze through tiny spaces,” Ramunas described, explaining how the mice quickly and consistently dislodged their packs. “There was no way to keep the backpacks on them.”
This challenge left one option: implantable pumps.
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