Dataset Information

Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-?/SMAD2 and PI3K/Akt pathways.

ABSTRACT: In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-?1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-?/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-?/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-?/SMAD2 and PI3K/AKT pathways.

SUBMITTER: Jun EK

PROVIDER: S-EPMC3907828 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-β/SMAD2 and PI3K/Akt pathways.

Jun Eun Kyoung EK Zhang Qiankun Q Yoon Byung Sun BS Moon Jai-Hee JH Lee Gilju G Park Gyuman G Kang Phil Jun PJ Lee Jung Han JH Kim Areee A You Seungkwon S

International journal of molecular sciences 20140106 1

In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but al ...[more]

PMID: 24398984

Similar Datasets

Project description:BackgroundThe balance of oral microbiomes is crucial to maintain oral health. Microecological imbalance can impair the function of mesenchymal stem cells (MSCs) and lead to delay wound healing. Probiotics is a promising prevention approach for the treatment of oral inflammatory diseases caused by a bacterial infection. However, the effect of probiotics on oral MSCs and wound healing is unclear. In the present study, we used one type of probiotics Lactobacillus reuteri extracts to determine whether bacterial extracts could regulate the functions of gingiva MSCs (GMSCs) and promote wound healing.MethodsLactobacillus reuteri was prepared with bacterial extracts using ultrasonic crushing apparatus. The effects of Lactobacillus reuteri extracts on GMSCs were tested using the cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of Lactobacillus reuteri extracts in the wound in mice, the wound position of bilateral mesial gingival of the maxillary first molar was established, the wound area with a size of 1?mm?×?2?mm and the full thickness gingiva was removed. Mice with wound were randomly distributed to two groups: injection of 0.9% NaCl (NS group) or injection of 50??g/ml bacterial extracts.ResultsWe discovered that 50??g/ml Lactobacillus reuteri extracts increased the capacities of migration, expression of stem cell markers, osteogenic differentiation, and proliferation of GMSCs. In addition, local injection of 50??g/ml bacterial extracts could promote wound-healing process in mice models. Mechanistically, we found that Lactobacillus reuteri extracts accelerated the process of wound healing via PI3K/AKT/?-catenin/TGF?1 pathway.ConclusionsThese data showed that Lactobacillus reuteri extracts could activate the potentials of GMSCs, thus promote wound healing. Our discovery provided the insight of the underlying mechanism activating functions of MSCs and identified Lactobacillus reuteri extracts as a potential therapeutic strategy for accelerating oral wound and potential application in the future dental clinic.

Project description:BackgroundStem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells.MethodsThe effect of MAPC-conditioned medium (MAPC-CM) on the capacity of keratinocytes, fibroblasts and endothelial cells to migrate and proliferate was determined in vitro using scratch wound closure and WST1 assay, respectively. The effect of MAPC-CM on collagen deposition and angiogenesis was also assessed using in vitro methods. Additionally, two excisional wounds were created on the dorsal surface of mice (n = 8/group) and 100 μL of 20× MAPC-CM were intradermally injected to the wound margins. Wound tissues were collected at 3, 7 and 14 days post-wounding and stained with H&E for microscopic analysis. Immunohistochemistry was performed to investigate inflammation, angiogenesis and collagen deposition in the wounds.ResultsSkin fibroblasts, keratinocytes and endothelial cells treated with MAPC-CM all showed improved rates of scratch closure and increased cellular proliferation. Moreover, fibroblasts treated with MAPC-CM deposited more collagens I and III and endothelial cells treated with MAPC-CM showed increased capillary tube formation. Murine excisional wounds intradermally injected with MAPC-CM showed a significant reduction in the wound area and an increase in the rate of reepithelialisation. The results also showed that inflammatory cell infiltration was decreased while an increase in angiogenesis, as well as collagens I and III expressions, was observed.ConclusionThese findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis. Development of stem cell-free therapy for the treatment of wounds may be a more clinically translatable approach for improving healing outcomes.

Dataset Information

Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-?/SMAD2 and PI3K/Akt pathways.

Publications

Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-β/SMAD2 and PI3K/Akt pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets