Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration

Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP(+)) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP(+)-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous.