Using cell sheets to regenerate mouse submandibular glands

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Nam K, Kim K, Dean SM, Brown CT, Davis RS, Okano T, Baker OJ

Tissue engineering strategies for craniofacial bone regeneration generally involve the actions of a scaffold material to support

The numerous effects of hyposalivation on the lifestyle and health status of affected patients motivates development of tissue engineering strategies for salivary gland regeneration. While some stem cell based strategies have been proposed, key challenges include maintenance of cells at the site of delivery to effect repair and damage to extracellular matrix proteins in the process of cell harvest after tissue culture. Temperature-responsive polymers grafted to tissue culture plates enable lifting of cell sheets after culture with maintenance of the extracellular matrix and cellular contracts that are typically lost upon enzymatic treatment to lift cells from traditional culture plates. Such cell sheets have been applied in tissue engineering strategies for regeneration of a variety of tissues. A recent article by Nam et al. explored the potential use of cell sheets to regenerate mouse submandibular glands. The study involved isolation of murine submandibular gland cells and culture to form cell sheets on temperature-responsive culture plates, and the authors compared single cell sheets and double cell sheets in vitro and in murine wound healing models. The authors found single cell sheets formed polarized features consistent with secretory epithelia, but lacked the three-dimensional glandular arrangement that could be achieved with double cell sheets. While single and double cell sheets both demonstrated an agonist-mediated response in vitro, the response was stronger from double cell sheets. Single and double cell sheets promoted submandibular gland wound healing in a murine model after 8 days, and the double cell sheets promoted improved tissue integrity and functionality.  Overall, the article suggests that cell sheet-based approaches present potential for salivary gland regeneration, with double sheet delivery approaches facilitating improved tissue function.

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