Three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes transdifferentiation of BM-MSCs.

Victims with extensive and deep burns are unable to regenerate eccrine sweat glands. Combining of stem cells and biomimetic ECM to generate cell-based 3D tissues is showing promise for tissue repair and regeneration. We co-cultured BrdU-labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) and eccrine sweat gland cells in Matrigel for 2 weeks in vitro and then evaluated for BM-MSCs differentiation into functional eccrine sweat gland cells by morphological assessment and immunohistochemical double staining for BrdU/pancytokeratin, BrdU/ZO-2, BrdU/E-cadherin, BrdU/desmoglein-2, BrdU/Na(+)-K(+)-ATPase α, BrdU/NHE1 and BrdU/CFTR. Cells formed spheroid-like structures in Matrigel, and BrdU-labeled BM-MSCs were involved in the 3D reconstitution of eccrine sweat gland tissues, and the incorporated BM-MSCs expressed an epithelial cell marker (pancytokeratin), epithelial cell junction proteins (ZO-2, E-cadherin and desmoglein-2) and functional proteins of eccrine sweat glands (Na(+)-K(+)-ATPase α, NHE1 and CFTR). In conclusion, three-dimensional co-culture of BM-MSCs and eccrine sweat gland cells in Matrigel promotes the transdifferentiation of BM-MSCs into potentially functional eccrine sweat gland cells.