Stretch-activated ion channels in human neural stem cell mechanotransduction
Stem cells therapy aims to replace damaged tissue with healthy stem-cell-derived tissue. In the brain it is being pursued as a strategy to treat conditions such as multiple sclerosis, stroke, Parkinson’s disease and spinal cord injury. For the promise of stem cell therapy to be realized, one needs to be able to precisely control the conversion of stem cells into the required cell type, through a process called differentiation. For instance, how can neural stem cells be experimentally manipulated to become neurons rather than a housekeeping glial cells? Stem cells can detect the physical properties of the tissue surrounding them, such as its rigidity, and these properties strongly influence the process of differentiation. This project aims to answer the questions: how does a stem cell assess whether it is surrounded by a rigid or soft tissue? And how is this information factored into the decision to become a specific cell type? We address these problems in human neural stem cells by focusing on proteins that let ions pass through the cell membrane in response to mechanical stimulation. Successful completion of the project will provide new drug targets that can be exploited to manipulate stem cell commitment to alternative cell fates, with applications in regenerative medicine and tissue engineering.
The California Stem Cell Research and Cures Act of 2004 aims to translate stem cell research into clinical therapies. The Act notes that “About half of California’s families have a child or adult who has suffered or will suffer from a serious, often critical or terminal, medical condition that could potentially be treated or cured with stem cell therapies”. Successful stem cell therapy requires a better grasp of how stem cells differentiate into specialized cells. Here we study how environment mechanics instructs stem cell differentiation and aim to identify a key molecular player. We focus on neural stem cells, which could potentially cure conditions like multiple sclerosis, stroke, Parkinson’s disease and spinal cord injury. Our findings will offer new guidelines for improved stem cell differentiation. They will also shed light on how the rigidity of matrices and scaffolds used in tissue engineering affects the growth of reconstructed organs and tissues. Anticipated benefits to Californians include: 1. Better means for generating specific brain cells types for treating neurological diseases. 2. Application of similar techniques to stem cell therapy involving mesenchymal and embryonic stem cells. 3. New opportunities for drug discovery and screening, based on knowing a key molecule involved in stem cell fate. 4. Creation of biotechnology start-ups using our findings to improve tissue engineering and prosthetic implants. 5. Jobs creation in the biotechnology/health sector.