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Exosomes from antler stem cells alleviates MSC senescence and osteoarthritis

ABSTRACT: The therapeutic functions of stem cells were mainly depending on paracrine effects rather than their own proliferation and differentiation on site. In advantage of easy to collected from conditioned medium, have contents of cytokines, growth factors, signaling lipids, mRNAs, and regulatory miRNAs, exosomes from stem cells were considered to be a promising material for stem cell-based cell-free therapies. In traditional Chinese medicine, antler extracts have been used to alleviates aging and aging related diseases. We have demonstrated that exosomes from antler stem cells (ASCs), the source of the annual full regeneration of deer antler, could alleviate cellular senescence and aging related diseases. With exosomes treatment, the senescent phenotype of primary MSCs and hMSCs at late passage were significantly mitigated. When injected into articular cavity, exosomes from ASCs markedly promote joint function recovery and bone and cartilage regeneration. By LC-MS/MS assay, we found that exosomes from ASCs contain various proteins which in the regulation of biological processes including cell proliferation and migration, immunoregulation, wound healing and angiogenesis. With the advantages of abundant sources, low risk of tumorigenicity and immunogenicity, exosomes from ASCs may consider as a promising bio-material for cell-free therapies in the future.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE172430 | GEO | 2021/04/21

REPOSITORIES: GEO

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Project description:As the only known mammalian organ that can fully and annually regenerate, deer antler has significant advantages over lower-order animal models when investigating the control of stem cell-based organ regeneration. Antler regeneration is known to be initiated and maintained by neural crest-derived stem cells in different states of activation. Antler stem cells can therefore be used as a model system to study the proteins and pathways involved in the maintenance of a stem cell niche and their activation and differentiation during organ formation. In the current study, the MSC markers CD73, CD90 and CD105 were examined within the antler tip. Label-free quantification was performed to investigate the protein profiles of antler stem cells under different stages of activation and included: dormant pedicle periosteum (DPP), antler growth center (GC), post-active stem cells from mid-beam antler periosteum (MAP), and deer facial periosteum (FP) as a control (n = 3 per group). PEAKS and IPA software were used to analyze the proteomic data. Our research confirmed the central role of stem cell activation in the development of this mammalian organ by localizing the MSC markers within the antler growth center. Label-free quantification revealed that the greatest number of unique proteins (eighty-seven) was found in the growth center tissue. There were only 12 proteins found with expression levels that significantly differed between DPP and FP. Protein profiles of these two groups indicated that antler stem cells may use similar mechanisms to maintain dormancy within a stem cell niche. The number of significantly regulated proteins between DPP, MAP and GC was 153. Among them, the majority were upregulated in the growth center. Activation of antler stem cells was associated with a number of biological processes and signaling pathways such as Hippo and canonical Wnt signaling. This work identifies the key canonical pathways, molecular/cellular functions and upstream regulators involved in mammal organ regeneration.