Differentiation of Skin Derived Stem Cells Into Bladder Smooth Muscle Cells

Purpose

Cystoplasty is used for repair of congenital abnormalities such as bladder exstrophy or treatment of acquired conditions such as neurogenic bladder. Skin derived stem cells (SKPs) are neural crest derived progenitors that retain the ability to differentiate into a variety of mesenchymal and neuronal cell types and could be extremely useful for bladder augmentation. We therefore tested the ability of SKPs to differentiate into bladder smooth muscle cells (BSMcell), a mesenchymal cell type, by exposing them to microenvironments that stimulate proliferation or differentiation of BSMcells.

Material and Methods

Rat SKPs were injected into ex vivo organ cultures of either mouse embryonic bladders or adult rat bladders exposed to mechanical strain. Alternatively, SKPs were exposed to different patterns of mechanical strain in vitro. Expression of smooth muscle specific markers was analyzed by immunofluorescence microscopy (SMactin, desmin, SMmyosin) and real time PCR (SMactin, SMmyosin, SM22, calponin, myocardin).

Results

SKPs that were injected into embryonic (E12.5) mouse bladders integrate into the developing muscle and urothelial layer and express SMactin and desmin. SKPs injected into stretch injured adult bladders primarily integrate into the urothelium and the interstitial spaces; few SKPs express BSMcell specific markers. Exposure of SKPs to sustained or sinusoidal patterns of stretch modifies expression of BSMcell specific markers.

Conclusions

SKPs can differentiate into BSMcells when provided with adequate microenvironmental cues such as the embryonic bladder and could potentially be used for bladder augmentation surgery.

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