The Human Umbilical Cord Tissue-Derived MSC Population UCX^®Promotes Early Motogenic Effects on Keratinocytes and Fibroblasts and G-CSF-Mediated Mobilization of BM-MSCs when Transplanted In Vivo

Abstract

Mesenchymal stromal cells (MSCs) play an important role in tissue regeneration mainly through the secretion of trophic factors that enhance the repair of damaged tissues. The main goal of this work was to study the paracrine mechanisms by which an umbilical cord tissue-derived MSC population (UCX(®)) promotes the migration capacity of human dermal fibroblasts and keratinocytes, which is highly relevant for skin regeneration. Furthermore, the differences between paracrine activities of MSCs from the umbilical cord tissue and the bone marrow (BM-MSCs) were also evaluated. In vitro scratch assays revealed that conditioned media (CM) obtained from both growing and stationary-phase UCX(®) cultures induced human dermal fibroblast (HDF) and keratinocyte (HaCaT) migration. These assays showed that the motogenic activity of UCX(®) CM to HaCaTs was significantly higher than to HDFs, in opposition to the effect seen with CM produced by BM-MSCs that preferentially induced HDF migration. Accordingly, a comparative quantification of key factors with vital importance in the consecutive stages of wound healing revealed very different secretome profiles between UCX(®) and BM-MSCs. The relatively higher UCX(®) expression of EGF, FGF-2, and KGF strongly supports early induction of keratinocyte migration and function, whereas the UCX(®)-specific expression of G-CSF suggested additional roles in mobilization of healing-related cells including CD34(-)/CD45(-) precursors (MSCs) known to be involved in tissue regeneration. Accordingly, in vitro chemotaxis assays and an in vivo transplantation model for chemoattraction confirmed that UCX(®) are chemotactic to CD34(-)/CD45(-) BM-MSCs via a cell-specific mobilization mechanism mediated by G-CSF. Overall, the results strongly suggest different paracrine activities between MSCs derived from different tissue sources, revealing the potential of UCX(®) to extend the regenerative capacity of the organism by complementing the role of endogenous BM-MSCs.

Hypoxia enhances the wound-healing potential of adipose-derived stem cells in a novel human primary keratinocyte-based scratch assay

“…Previously, when assessing the wound healing effect of ASCs and other mesenchymal stem cells on keratinocytes in a scratch assay, a combination of conditioned media from stem cells and the spontaneously transformed aneuploid immortal keratinocyte cell line, HaCaT, has often been preferred (3,7,8). However, as transformed cells often display an altered response to growth factors and cytokines compared to their non-cancerous counterparts (9), and may respond in a hyperactive manner to hypoxia-induced factors, such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) (9–11), this cell line may not be the best option to predict in vivo responses.…”

Addition of Autologous Mesenchymal Stem Cells to Whole Blood for Bioenhanced ACL Repair Has No Benefit in the Porcine Model

“…Linear stiffness values of 32% of the intact ACL values in this study were comparable to earlier results that averaged between 20% and 33%. 28, 31, 40 The linear stiffness results are encouraging as this is the parameter that tissue engineers attempt to replicate as ligaments and tendons routinely operate in the range that is less than 10% of the failure load when patients perform activities of daily living. 6 …”

Stem Cells in Skin Wound Healing: Are We There Yet?

“…Curiously, BM-MSCs-conditioned medium (CM) improved macrophage recruitment by potentiating secretion of macrophage inflammatory protein-1alpha/beta and erythropoietin. 26 BMMSCs, 26,54 hASCs, 55 and umbilical cord mesenchymal stem cells 56 were also shown to release KGF, fibroblast growth factor 2, and epidermal growth factor. These promoted KCs migration in vivo, significantly influencing wound re-epithelialization.…”

“…These promoted KCs migration in vivo, significantly influencing wound re-epithelialization. 26,55,56 Likewise, the impact on wound angiogenesis/ vascularization at the wound site was also associated to vascular endothelial growth factor (VEGF) secreted by mouse bone marrow mesenchymal stem cells 26 and hASCs. 55 Other important regulators of angiogenesis, namely angiogenin, VEGF-A, and leptin, were also identified in hASCs, human bone marrow mesenchymal stem cells, DSCs, and dermal papilla cells (DPCs) secretome.…”