Stem Cell Engineering
The in vivo stem cell microenvironment is critical for providing signaling cues to regulate the balance between quiescence and activation or differentiation of stem cells and to control tissue formation and repair. The effects of these cues are especially important to understand in the context of tissue engineering, where stem cells are often integrated into tissue-engineered constructs. Thus, there is a significant need to understand the effects of cues from the microenvironment on stem cell behavior, including migration and differentiation. Traditionally, the field of stem cell biology has largely focused on gene regulated-differentiation via biochemical cues. However, in vivo stem cells are also presented with many physical cues, such as tissue stiffness, shear stress from fluid flow, and tissue topography. Remarkably, these types of physical cues have recently been identified as regulators of stem cell differentiation. We believe that understanding stem cell mechanobiology (i.e., how stem cells convert mechanical cues into biological responses) will enable more efficient and effective engineering of stem cells for therapeutic applications in the clinic.
For example, we are currently investigating the mechanobiology of mesenchymal stem cells (MSCs), which are found in bone marrow and other tissues. One of MSCs’ unique properties is their ability to differentiate into many different cell types (e.g., bone, cartilage, muscle) and, and as a result, they are currently involved in an increasing number of clinical trials which capitalize on their therapeutic potential for tissue repair in many diseases. As such, they are commonly injected intravenously into patients through regenerative medicine-based treatments, or incorporated into tissue engineered scaffolds. However, a major limitation in the field of regenerative medicine is lack of knowledge about mechanisms of MSC biodistribution, and why only small fractions of MSCs are detected in target tissues following injection into the patient. We are using engineered microenvironments to test hypotheses related to the migration and differentiation of MSCs in response to various physical and biochemical cues encountered during homing or integration into tissue engineered scaffolds.
Check out our recent paper on how physical confinement alters mesenchymal stem cell migration.
Check out our recent paper on the effects of culture conditions on MSC exosome biogenesis and vascularization activity.
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