Dr. Fan Yang

A bioengineer by training, Dr. Fan Yang works at the interface of materials science, biology, engineering, and medicine. She is the Director and PI for Stem Cells and Biomaterials Engineering Laboratory at Stanford University, jointly supported by Departments of Orthopaedic Surgery and Bioengineering. Dr. Yang has extensive expertise in developing novel biomaterials and stem cell-based therapeutics for musculoskeletal tissue engineering, or engineering 3D in vitro cancer models for drug screening and mechanistic discovery. Her research group is particularly interested in developing biomaterials and cell-based therapeutics to improve regeneration of various musculoskeletal tissues including bone, cartilage, tendon, blood vessels etc.

Learn more about Dr. Yang here: https://profiles.stanford.edu/fan-yang

You can also find more photos (individual or group) from Dr. Fan's lab website: Fan Yang Group Members and Fan Yang Group Life

The Role of Movement in Determining the Fate of Stem Cells

The Journey of Stem Cells
Stem cells are unique. They have the potential to transform into different types of cells, making them incredibly valuable for medical research and treatments. However, the journey from a stem cell to a specialized cell is intricate and influenced by numerous factors, including their physical movement.
Why Movement Matters
Dr. Fan Yang and her team have discovered that the way stem cells move can significantly impact their fate. By observing over one thousand hours of videos of stem cells in motion, these scientists discovered a previously unknown pattern of cell movement-which they term “cell tumbling”- that plays a crucial role in stem cell differentiation in 3D.
The Science of Tumbling
Fan Yang's lab is dedicated to developing stem cell and biomaterials-based therapies that regenerate human tissues lost to disease or aging. In a groundbreaking study, her team focused on transforming stem cells into cartilage. "Cartilage is one of the most commonly injured tissues in the human body, yet has very limited capacity to regenerate," Yang explained.
To study cells in a 3D environment that closely approximates what they experience in the body, researchers embed them in small tubes of water-based gelatin. Traditionally, the gels used for this purpose are formed via covalent crosslink, which restrain cell movements. However, Yang's lab developed a new type of gel called sliding hydrogel, which provide molecular scale mobility that allow cells to reorganize their local niche, and exhibit minute-scale, rapid localized cell movements.
Surprising Discoveries
In an earlier study, Dr. Yang's team, including lead researcher Ayushman, found that stem cells embedded in the new sliding gel differentiated into cartilage much faster than those in conventional gels. "It's a very striking difference," Ayushman noted. "That triggered our curiosity, and we decided to dig deeper."
After analyzing a thousand hours of cell footage and conducting numerous experiments, the researchers believe the difference comes down to cell movement. They observed that stem cells don't just passively sit in the 3D niche. Instead, they actively interact with their 3D environment through physical movements such as pushing and pulling, which result in a unique dancing-like “cell tumbling” behavior. Using sliding hydrogels, the team demonstrates cell tumbling enhances stem cell differentiation towards multiple lineages (cartilage, bone, fat). Furthermore, they showed cell tumbling is a universal cell behavior that can occurs in multiple commonly used hydrogel platforms. Consistently, hydrogels that promote cell tumbling promotes stem cell differentiation in 3D via mechanotransduction. Importantly, the findings from this paper could be broadly used to enhance stem cell differentiation towards many tissue types such as heart cells, neurons, or other specialized cells.
Implications for Medical Research
Understanding the influence of local matrix mechanical cues of 3D matrix on stem cell tumbling and differentiation could revolutionize regenerative medicine and tissue engineering. This knowledge can help accelerate the translation of stem cell-based therapy for various diseases, by improving the efficiency and effectiveness of differentiation process.
Looking Ahead
The above research led by Dr. Fan Yang involved a collaboration across a team of basic and clinician scientists from six departments, and is a testament to the innovative spirit of the institution. As they continue to study these fascinating cell movements, they move closer to unlocking the full potential of stem cells for revolutionizing future medicine.
Broad impact in finding cures for degenerative joint diseases
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by inflammation and cartilage degradation. Current treatments focus on alleviating symptoms such as pain and inflammation, but no FDA-approved therapies exist that can halt or reverse the disease. While the biochemical drivers of OA have been extensively studied, the impact of matrix mechanical cues on OA progression remains largely unexplored.
In addition to stem cells, Yang's lab has recently published another paper showing that cell tumbling can occur in osteoarthritic chondrocytes too. Using sliding hydrogels, the same hydrogel platform reported in the Nature Materials paper, they demonstrated that increased cell tumbling of osteoarthritic cells reduces its inflammatory phenotype. Importantly, the team demonstrate that targeting nuclear mechanosensing and chromatin accessibility with a specific drug effectively reduces OA inflammation in 3D hydrogels. These novel findings shed light on the previously underappreciated role of extracellular matrix (ECM) mechanics in OA progression and highlight the potential for developing disease-modifying therapies that leverage epigenetic and mechanosensing-based mechanisms.

This study is available in PubMed.