Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes

Abstract

Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CM) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression. Keratinocytes cultured in CM showed a significant increase in cell number compared to serum-free cultures and further significant increases in hypoxic CM. Assessment of ADSC gene expression on a cytokine array showed a range of wound healing cytokines expressed and under stringent hypoxic and serum-free conditions was upregulated (VEGF A, MMP9, Tissue Factor, PAI-1) or downregulated (CXCL5, CCL7, TNF-α). Several of these may contribute to the activity of conditioned media on the keratinocytes with potential applications in TM perforation repair. VEGFA protein was confirmed by immunoassay to be increased in conditioned media. Together with gene regulation associated with hypoxia in ADSCs, this study has provided several strong leads for a stem cell-derived approach to TM wound healing.

Histological and Behavioral Alterations Following hADSCs Intravenous Administration in Alzheimer’s Rat Model

“…There are various mechanisms for improving the effects of stem cells in AD. It had been confirmed that AD-SCs could have therapeutic effects by mediating paracrine signaling of angiogenesis, inflammation, cell homing, and cell survival (26,29,30). The ADSCs administration presented raised levels of growth factors like basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and neurotrophic factors such as glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) (16,31,32).…”

Function and Therapeutic Potential of Mesenchymal Stem Cells and Their Acellular Derivatives on Non-Healing Chronic Skin Ulcers

“…MSC acellular derivatives are being rigorously investigated as a means to accelerate the proliferation, migration and differentiation of keratinocytes and dermal fibroblasts, in order to regulate the complex interactions that occur during wound healing [123,167,168]. Scratch assays revealed that, relative to the control (medium with serum), dermal fibroblasts and keratinocytes enhanced their rate of wound closure when exposed to MSC acellular derivatives by increasing their migration instead of their proliferation rates [167].…”

Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

“…Human adipose-derived stem cells (ADSCs) are multidirectional differentiation potential stem cells extracted from adipose tissue. ADSCs can migrate to a damaged site and differentiate into skin appendages to repair damaged skin through their multidirectional differentiation potential [5][6][7][8]. At the same time, ADSCs can secrete various growth factors to inhibit the inflammatory response, accelerate wound angiogenesis, and promote wound healing [9].…”