Directing Stem Cells for Tissue Repair
During development and degenerative processes, communication between multiple different cell types along with physicochemical cues from an evolving ECM direct progenitor stem cells to specific lineages. Additionally, complex cell and ligand arrangements along with ECM mechanical properties play a critical role in regulating tissue and cell function.
Mesenchymal stem cells (MSCs), progenitor cells for bone and cartilage, show regenerative potential for nearly all tissue types, cartilage and meniscus regeneration and repair for osteoarthritis and injury are particularly promising applications. In these tissues, interactions between different cell types play an important role in modulating cell function. However, the role of cell-cell signaling in determining MSC fate. remains incompletely understood. We seek to understand how cell architecture alters cell fate through systematic and complete study of MSC interactions with other cells in both healthy and dysfunctional states.
The ECM mechanical and chemical properties provide environmental feedback that guides cell fate and directs cell migration. In the case of osteoarthritis, remodeling of the ECM results in changes to mechanical and chemical properties characterized by stiffening and loss of collagen and glycosaminoglycans. Hydrogel systems have been developed that have responsive elements to release growth factors or modulate the bulk properties in order to elicit desired responses (e.g., recellularization/wound healing, differentiation). Despite these advances, mimicking temporal ECM modulation remains challenging, especially when one considers the heterogeneity of the ECM, where a multitude of different proteins organized in nano-to-micro domains modulate cell and tissue function.
Therefore, it is of paramount interest to develop cellular niche models that enable rational temporal control over local mechanics and ligand arrangement with nanoscale precision; such models would enable one to better replicate and study developmental and injury repair processes and develop materials that enhance recellularization and tissue formation. The Meckes group works to develop nanomaterials with spatiotemporally arranged properties, which will be used to mimic disease progression and tissue formation processes to determine mechanisms for recellularizing and repairing diseased tissue.