Background and Aim: Human umbilical cord mesenchymal stem cells (hUC-MSCs) and its conditioned medium (CM) promote wound healing. This study investigated the wound healing potential of hUC-MSC CM in vitro and in vivo using diabetic animal models. Materials and Methods: The CM from hUC-MSC CM prepared under hypoxic conditions (hypoxic hUC-MSC) was evaluated for stimulating rat fibroblast growth, collagen production (in vitro), and wound healing in animal models (in vivo). An excision wound on the dorsal side of the diabetes-induced rats was established, and the rats were randomly divided into non-treatment, antibiotic, and hypoxic hUC-MSC CM groups. The cell number of fibroblasts and collagen secretion was evaluated and compared among the groups in an in vitro study. By contrast, wound size reduction, width of re-epithelialization, and the collagen formation area were assessed and compared among the groups in an in vivo study. Results: CM under hypoxic conditions contained a higher concentration of wound healing-related growth factors. Hypoxic hUC-MSC CM could facilitate fibroblast cell growth and collagen synthesis, although not significant compared with the control group. Re-epithelialization and collagen production were higher in the hUC-MSC CM group than in the antibiotic and non-treatment groups. Conclusion: Hypoxic hUC-MSC CM possessed more positive effects on the wound healing process based on re-epithelialization and collagen formation than antibiotic treatment did.

Skeletal muscle is one of the most abundant and dynamic tissues of the body, with a strong regenerative capacity. Muscle injuries can occur as a result of a variety of events, including tissue ischaemia. Lower limb ischaemia occurs when there is an insufficient nutrient and oxygen supply, often caused by stenosis of the arteries due to atherosclerosis. The aim of this study was to develop and validate a multiparametric scoring tool for assessing ischaemia severity in skeletal muscle in a commonly used preclinical animal model. Tissue ischaemia was surgically induced in mice by ligation and excision of the femoral artery. Calf muscles were carefully dissected, prepared for histological analysis, and scored for inflammation, fibrosis, necrosis, adipocyte infiltration, and muscle fibre degeneration/regeneration. Kendall’s coefficient of concordance (W) showed a very good agreement between the appraisers when scoring each individual histological feature: inflammation (W = 0.92, p ≤ 0.001 ), fibrosis (W = 0.94, p ≤ 0.001 ), necrosis (W = 0.77, p ≤ 0.001 ), adipocyte infiltration (W = 0.91, p ≤ 0.001 ), and fibre degeneration/regeneration (W = 0.86, p ≤ 0.001 ). Intrarater agreement was also excellent (W = 0.94 or more, p ≤ 0.001 ). There was a statistically significant negative association between the level of muscle ischaemia damage and the calf muscle weight and skeletal muscle fibre diameter. Here, we have developed and validated a new multiparametric, semiquantitative scoring system for assessing skeletal muscle damage due to ischaemia, with excellent inter- and intrarater reproducibility. This scoring system can be used for assessing treatment efficacy in preclinical models of hind limb ischaemia.

BACKGROUND: Secretome production by stem cells depends on their culture conditions such as oxygen concentration and the composition of the culture media. In this study, we investigated the secretion of neurotrophic growth factors of human umbilical cord mesenchymal stem cells (hUC-MSCs) in amino acid-rich culture medium and under hypoxic condition.METHODS: hUC-MSCs were cultured in normoxic and various hypoxic (1%, 5%, 10%) conditions in an amino acid-rich culture medium. The end-point parameters (cell proliferation and survival, cell morphology and growth factor secretion) were measured at 3 time-points (48 hours, 72 hours and 96 hours). ELISA-based methods were used for neurotrophic factors detection, including neurotrophic growth factor (NGF), vascular endothelial factor (VEGF), and brain-derived neurotrophic factor (BDNF).RESULTS: NGF secretion was not detectable at any time points both in normoxia and hypoxia. BDNF secretion under normoxia was induced at 48 h time point and reached the highest level at an average of 181.9±13.01 pg/mL at 96 hours, whereas hypoxia exposure to hUC-MSCs only induced the BDNF secretion at low level. VEGF secretion was barely detectable in normoxic condition. However, VEGF secretion reached the highest level at an average of 7707.55±2110.85 pg/mL in 5% hypoxia at 96 hours.CONCLUSION: Combination of amino acid-rich culture medium and hypoxia condition dramatically induced high VEGF secretion by hUC-MSCs, especially at 5% hypoxia, induced mild BDNF secretion and had no effect toward NGF secretion.KEYWORDS: human umbilical cord mesenchymal stem cells, neurotrophic growth factor, amino acid-rich, hypoxia

No abstract

No abstract