Regenerative potential of partially differentiated mesenchymal stromal cells in a mouse model of a full-thickness skin wound
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Date
2018-08-31
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Abstract
Mesenchymal stromal cells (MSCs, known as mesenchymal stem cells) are considered to be a promising therapeutic
tool for many diseases. But it is still unclear which cells are more efficient and safe for wound healing and
tissue regeneration for clinical applications: undifferentiated, partially differentiated stem cells or differentiated
cells. In this study, we modified MSCs with keratinocyte-conditioned medium (KCM) and examined MSCs, partially
differentiated MSCs (PMSCs) and differentiated cell migration, accumulation in the wounded area as well
as cell regenerative efficiency in a full-thickness skin wound model. In addition to that, the impact of intradermal
and intravenous cell delivery methods of wound healing was evaluated. C57BL/6J mouse compact bone MSCs
were treated with a KCM for 14 days. Flow cytometry analysis showed the appearance of keratinocyte surface
markers which were absent in MSCs, whereas the specific markers for MSCs were lost. Cells were injected either
intravenously or intradermally in C57BL/6J mice. Wound closure, cell migration and accumulation in the wounded
area were further analysed. Wound healing was assessed by the rate of wound closure and by histological evaluation.
Cells were monitored using optical imaging. We demonstrated that PMSCs showed morphology similar to
keratinocyte cells, had enhanced migration and increased survival at the site of injury. PMSCs had a beneficial
effect on wound healing and tissue regeneration. This effect was reinforced when these cells were injected intravenously.
Due to their partial differentiation status, we assume that PMSCs can differentiate more rapidly into
epidermal cell lineages thus causing faster and qualitatively improved wound healing.
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Keywords
Mesenchymal stromal cells, Partial differentiation, Keratinocyte-conditioned medium, Skin regeneration