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Peripheral nerve injuries require a complex set of signals from cells, macrophages, and the extracellular matrix (ECM) to induce regeneration across injury sites and achieve functional recovery. Schwann cells (SCs), the major glial cell in the peripheral nervous system (PNS), are critical to nerve regeneration due to their inherent capacity for altering phenotype post-injury to facilitate wound healing. The ECM plays a vital role in wound healing as well as regulating cell phenotype during tissue repair. To examine the underlying mechanisms between the ECM and SCs, this work sought to determine how specific ECM cues regulate the phenotype of SCs. To address this, SCs were cultured on polydimethylsiloxane substrates of a variable Young's modulus coated with ECM proteins. Cells were analyzed for spreading area, proliferation, cell and nuclear shape, and c-Jun expression. It was found that substrates with a stiffness of 8.67 kPa coated with laminin promoted the highest expression of c-Jun, a marker signifying a "regenerative" SC. Microcontact printed, cell adhesive areas were then utilized to precisely control the geometry and spreading of SCs and by controlling spreading area and cellular elongation, expression of c-Jun was either promoted or downregulated. These results begin to address the significant interplay between ECM cues and phenotype of SCs, while offering a potential means to enhance PNS regeneration through cellular therapies.
This article was published in the following journal.
Name: Journal of tissue engineering and regenerative medicine
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A discoidin domain receptor for FIBRILLAR COLLAGEN that functions in a variety of cellular processes. For example, it regulates cell attachment to the EXTRACELLULAR MATRIX, remodeling of the extracellular matrix, CELL MIGRATION; CELL DIFFERENTIATION; CELL PROLIFERATION; and CELL SURVIVAL.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
A CCN protein family member found at high levels in NEPHROBLASTOMA cells. It is found both intracellularly and in the EXTRACELLULAR MATRIX and may play a role in the regulation of CELL PROLIFERATION and EXTRACELLULAR MATRIX synthesis.
An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of DESMOSOMES. They are composed of specialized areas of the plasma membrane where INTERMEDIATE FILAMENTS bind on the cytoplasmic face to the transmembrane linkers, INTEGRINS, via intracellular attachment proteins, while the extracellular domain of the integrins binds to EXTRACELLULAR MATRIX PROTEINS.
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