Affiliation:
1. National University of Singapore
2. Singapore-MIT Alliance for Research and Technology Centre
Abstract
Abstract
Background
Elderly patients develop pressure ulcers that are very difficult to treat and current treatments have several limitations. Native skin stem cells diminish with age and may explain poor skin renewal in the elderly. Hence, an exogenous supply of stem cells to wounds in the elderly may produce a successful therapy. We evaluated the wound healing potential of an aloe vera-polycaprolactone nanocarrier impregnated with human Wharton’s jelly stem cells (hWJSCs + AV/PCL) or its conditioned medium (hWJSC-CM + AV/PCL) on elderly human skin using in vitro wound assays and on excisonal wounds created in an elderly preclinical mouse model.
Methods
hWJSCs and human skin fibroblasts (HSFs) were derived and characterized using our previously published protocols. The influence of hWJSC-CM on elderly human skin fibroblasts (eHSFs) were compared with that of young HSFs (yHSFs) and untreated eHSF controls. The healing of excisonal wounds created in elderly mice over a 21 day period was evaluated using various methods.
Results
Scratch wounds of hWJSC-CM-treated eHSFs completely closed by day 2 compared to untreated eHSF controls. Collagen and elastin levels were significantly increased while senescence-related genes were significantly downregulated in hWJSC-CM-treated eHSFs compared to untreated eHSFs. Angiogenesis assays produced significantly greater tubule numbers and ring formation in the presence of CM from hWJSC-CM-treated eHSFs. Excisional wounds in elderly mice treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL completely healed by day 21 and wound closure rates were significantly greater compared to controls. Histology of elderly mice wounds treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL showed changes in skin structure. Epidermal and dermal thickness, CD31 and gene expression levels of ECM, collagen, angiogenesis, scarless, granulation and immune cell chemoattraction were significantly greater in elderly mice treated with hWJSC + AV/PCL and hWJSC-CM + AV/PCL.
Conclusions
The results confirmed that hWJSCs in combination with the stem cell niches in nanoscaffolds and the antimicrobial properties of aloe vera provide an attractive wound dressing patch for treatment of chronic wounds in the elderly.
Publisher
Research Square Platform LLC
Reference71 articles.
1. Salleh NAM. (2017) Jobs for the future. The Straits Times, B4, May 1.
2. Pieper B. Mechanical forces: pressure, shear, and friction. Bryant RA, Nix DP Acute and chronic wounds: current management concepts 3rd ed St Louis: Mosby. 2007:205 – 34.
3. Age and Its Effect on Wound Healing. (2014) Advanced Tissue, Nov 6.
4. Immune aging in diabetes and its implications in wound healing;Moura J;Clin Immunol,2019
5. Age decreases endothelial progenitor cell recruitment through decreases in hypoxia-inducible factor 1α stabilization during ischemia;Chang EI;Circulation,2007