Pax7 Expressing Cells Contribute to Dermal Wound Repair, Regulating Scar Size through a ß-Catenin Mediated Process.
Journal - Stem cells (Dayton, Ohio) (United States )
During skin wound healing, fibroblast-like cells reconstitute the dermal compartment of the repaired skin filling the wound gap. A subset of these cells are transcriptionally active for ß-catenin/T-cell factor (TCF) signaling during the proliferative phase of the repair process, and ß-catenin levels control the size of the scar that ultimately forms by regulating the number of dermal fibroblasts. Here, we performed cell lineage studies to reveal a source of the dermal cells in which ß-catenin signaling is activated during wound repair. Using a reporter mouse, we found that cells in the early wound in which TCF-dependent transcription is activated express genes involved in muscle development. Using mice in which cells express Pax7 (muscle progenitors) or Mck (differentiated myocytes) are permanently labeled, we showed that one quarter of dermal cells in the healing wound are Pax7 expressing progeny, but none are Mck progeny. Removing one allele of ß-catenin in Pax7 expressing progeny resulted in a significantly smaller scar size with fewer Pax7 expressing progeny cell contributing to wound repair. During wound healing, ß-catenin activation causes muscle satellite cells to adopt a fibrotic phenotype and this is a source of dermal cells in the repair process. STEM CELLS 2011;29:1371-1379.Copyright © 2011 AlphaMed Press.
Ultrafast Mid-IR Laser Scalpel: Protein Signals of the Fundamental Limits to Minimally Invasive Surgery.
Journal - PloS one (United States )
Lasers have in principle the capability to cut at the level of a single cell, the fundamental limit to minimally invasive procedures and restructuring biological tissues. To date, this limit has not been achieved due to collateral damage on the macroscale that arises from thermal and shock wave induced collateral damage of surrounding tissue. Here, we report on a novel concept using a specifically designed Picosecond IR Laser (PIRL) that selectively energizes water molecules in the tissue to drive ablation or cutting process faster than thermal exchange of energy and shock wave propagation, without plasma formation or ionizing radiation effects. The targeted laser process imparts the least amount of energy in the remaining tissue without any of the deleterious photochemical or photothermal effects that accompanies other laser wavelengths and pulse parameters. Full thickness incisional and excisional wounds were generated in CD1 mice using the Picosecond IR Laser, a conventional surgical laser (DELight Er:YAG) or mechanical surgical tools. Transmission and scanning electron microscopy showed that the PIRL laser produced minimal tissue ablation with less damage of surrounding tissues than wounds formed using the other modalities. The width of scars formed by wounds made by the PIRL laser were half that of the scars produced using either a conventional surgical laser or a scalpel. Aniline blue staining showed higher levels of collagen in the early stage of the wounds produced using the PIRL laser, suggesting that these wounds mature faster. There were more viable cells extracted from skin using the PIRL laser, suggesting less cellular damage. ß-catenin and TGF-ß signalling, which are activated during the proliferative phase of wound healing, and whose level of activation correlates with the size of wounds was lower in wounds generated by the PIRL system. Wounds created with the PIRL systsem also showed a lower rate of cell proliferation. Direct comparison of wound healing responses to a conventional surgical laser, and standard mechanical instruments shows far less damage and near absence of scar formation by using PIRL laser. This new laser source appears to have achieved the long held promise of lasers in minimally invasive surgery.