Value Proposition
· Preserve bone-forming potential (osteogenic phenotype) in soft tissue environments
· Reduces immune rejection by promoting an immunosuppressive macrophage response
· Enables preconditioning of stem cells for enhanced engraftment success
· Applicable to a wide range of regenerative medicine and tissue engineering therapies
· Introduces a novel biophysical cue (fluid viscosity) for controlling stem cell behavior
· Supports long-term therapeutic efficacy through osteogenic memory imprinting
Technology Description
· Researchers at Johns Hopkins have developed a novel system that uses fluid viscosity to regulate the behavior and development of human mesenchymal stem cells (hMSCs), with applications in tissue regeneration and engraftment. This approach demonstrates that increasing the thickness of the fluid surrounding stem cells can shift their development toward bone-forming characteristics, even when placed on soft materials that would typically promote fat cell formation. The underlying mechanism involves a cascade of cellular responses that collectively promote osteogenic differentiation. Importantly, this viscosity-based method also enhances stem cell spreading and adhesion, and induces an immunosuppressive response in macrophages, which may help reduce immune rejection after transplantation. These findings position extracellular fluid viscosity as a powerful biophysical cue for improving stem cell therapies, offering new strategies for enhancing cell survival, function, and integration in regenerative medicine.
Unmet Need
· Current stem cell therapies using hMSCs face major challenges, including poor cell survival, loss of bone-forming potential, and immune rejection after transplantation. These limitations reduce the effectiveness of hMSC-based treatments for tissue regeneration and bone repair. There is a pressing need for strategies that can enhance stem cell durability, preserve therapeutic function, and minimize immune rejection—especially in regenerative applications where long-term cell performance is critical. Additionally, many tissue repair therapies lack methods to precondition cells in ways that improve their integration and survival in complex biological environments.
Stage of Development
· This technology is currently in the preclinical development stage, with strong in vitro evidence including:
o Elevated fluid viscosity encourages stem cells to take on an osteogenic phenotype (bone-like characteristics), even when placed on surfaces with specific stiffness and flexibility
o Mechanistic studies have identified the molecular pathways through which this phenotype is imprinted—providing insight into how viscosity influences stem cell fate.
o Additional findings demonstrate that elevated viscosity induces an immunosuppressive phenotype in hMSCs, suggesting broader therapeutic potential.
· The next phase of development will focus on in vivo validation, to confirm these in vitro results and assess translational relevance.
Data Availability
· Data available upon request.
Publication
Amitrano, A., Yuan, Q., Agarwal, B., Sen, A., Dance, Y. W., Zuo, Y., Phillip, J. M., Gu, L., &
Konstantopoulos, K. (2025). Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function. Science advances, 11(1), eadr5023. https://doi.org/10.1126/sciadv.adr5023
