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  • Chen, Shang  (8)
  • Han, Zhong-Chao  (8)
  • 1
    In: Acta Biomaterialia, Elsevier BV, Vol. 122 ( 2021-03), p. 199-210
    Type of Medium: Online Resource
    ISSN: 1742-7061
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2173841-5
    SSG: 12
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  • 2
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-01-22)
    Abstract: Chemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear. Methods Doxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing. Results MSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis. Conclusions Hsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2548671-8
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  • 3
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-12)
    Abstract: Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to have therapeutic potential for ischemic diseases and are considered an alternative to cell therapy. However, the low retention and poor stability of EVs post-transplantation in vivo remain obstacle prior to the clinical application of EVs. Methods This study was designed to investigate whether collagen matrix could increase the retention and stability of EVs and further improve the therapeutic effects in murine acute kidney injury (AKI) model. EVs were isolated from human placental MSCs (hP-MSC-EVs) and encapsulated in a collagen matrix. Then, we investigated whether collagen matrix can prolong the retention of EVs in vivo, further enhancing the therapeutic efficiency of EVs in AKI. Results Our results indicated that collagen matrix could effectively encapsulate EVs, significantly increase the stability of EVs, and promote the sustained release of EVs. Collagen matrix has improved the retention of EVs in the AKI model, which was proved by Gaussia luciferase (Gluc) imaging. The application of collagen matrix remarkably facilitated the proliferation of renal tubular epithelial cells in AKI compared with EVs alone. Moreover, collagen matrix could further augment the therapeutic effects of hP-MSC-EVs as revealed by angiogenesis, fibrosis and apoptosis, and functional analysis. Finally, we found that EVs play a therapeutic role by inhibiting endoplasmic reticulum (ER) stress. Conclusions Collagen matrix markedly enhanced the retention of EVs and further augmented the therapeutic effects of EVs for AKI. This strategy for improving the efficacy of EVs therapy provides a new direction for cell-free therapy.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2548671-8
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Stem Cell Research & Therapy Vol. 13, No. 1 ( 2022-12)
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-12)
    Abstract: Intravenous administration of mesenchymal stromal cells (MSCs) has an acknowledged competence of cardiac repair, despite a lack of systematic description of the underlying biological mechanisms. The lung, but not the heart, is the main trapped site for intravenously transplanted MSCs, which leaves a spatial gap between intravenously transplanted MSCs and the injured myocardium. How lung-trapped MSCs after intravenous transplantation rejuvenate the injured myocardium remains unknown. Methods MSCs were isolated from human placenta tissue, and DF-MSCs or Gluc-MSCs were generated by transduced with firefly luciferase (Fluc)/enhanced green fluorescence protein (eGFP) or Gaussia luciferase (Gluc) lactadherin fusion protein. The therapeutic efficiency of intravenously transplanted MSCs was investigated in a murine model of doxorubicin (Dox)-induced cardiotoxicity. Trans-organ communication from the lung to the heart with the delivery of blood was investigated by testing the release of MSC-derived extracellular vesicles (MSC-EVs), and the potential miRNA inner MSC-EVs were screened out and verified. The potential therapeutic miRNA inner MSC-EVs were then upregulated or downregulated to assess the further therapeutic efficiency Results Dox-induced cardiotoxicity, characterized by cardiac atrophy, left ventricular dysfunction, and injured myocardium, was alleviated by consecutive doses of MSCs. These cardioprotective effects might be attributed to suppressing GRP78 triggering endoplasmic reticulum (ER) stress-induced apoptosis in cardiomyocytes. Our results confirmed that miR-181a-5p from MSCs-derived EVs (MSC-EVs) inhibited GRP78. Intravenous DF-MSCs were trapped in lung vasculature, secreted a certain number of EVs into serum, which could be confirmed by the detection of eGFP + EVs. GLuc activity was increased in serum EVs from mice administrated with GLuc-MSCs. MiR-181a-5p, inhibiting GRP78 with high efficacy, was highly expressed in serum EVs and myocardium after injecting consecutive doses of MSCs into mice treated with Dox. Finally, upregulation or downregulation of miR-181a-5p levels in MSC-EVs enhanced or weakened therapeutic effects on Dox-induced cardiotoxicity through modulating ER stress-induced apoptosis. Conclusions This study identifies intravenously transplanted MSCs, as an endocrine reservoir, to secrete cardioprotective EVs into blood continuously and gradually to confer the trans-organ communication that relieves Dox-induced cardiotoxicity.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2548671-8
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  • 5
    In: iScience, Elsevier BV, Vol. 24, No. 11 ( 2021-11), p. 103243-
    Type of Medium: Online Resource
    ISSN: 2589-0042
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2927064-9
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  • 6
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-03-20)
    Abstract: The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment. Methods In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking. Results CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures. Conclusions CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2548671-8
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  • 7
    In: Extracellular Vesicle, Elsevier BV, Vol. 1 ( 2022-12), p. 100018-
    Type of Medium: Online Resource
    ISSN: 2773-0417
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 8
    In: eLife, eLife Sciences Publications, Ltd, Vol. 12 ( 2023-09-11)
    Abstract: Animals are made up of cells of different types, with each type of cell specializing on a specific role. But for the body to work properly, the different types of cells must be able to coordinate with each other to respond to internal and external stimuli. This can be achieved through signaling molecules, that is, molecules released by a cell that can elicit a specific response in other cells. There are many types of different molecules, including hormones and signaling proteins. Gases can also be potent signaling molecules, participating in various biological processes. Nitric oxide (NO) is a gas signaling molecule that can freely diffuse through the membranes of cells and has roles in blood vessel constriction and other disease processes, making it a promising therapeutic agent. Unfortunately, using artificial carriers to deliver nitric oxide to the organs and tissues where it is needed can lead to issues, including immune reactions to the carrier and long-term toxicity. One way to avoid these effects is by using cells to deliver nitric oxide to the right place. Huang, Qian, Liu et al. have used mesenchymal stem cells – which usually develop to form connective tissues such as bone and muscle – to develop a cell-based NO-delivery system. The researchers genetically modified the mesenchymal stem cells to produce a compound called β-GAL H363A . On its own β-GAL H363A does not do much, but in its presence, a non-toxic, non-reactive compound developed by Huang, Qian, Liu et al., called MGP, can drive the release of NO from cells. To confirm the usefulness of their cells as a delivery system, Huang, Qian, Liu et al. transplanted some of the genetically modified mesenchymal stem cells into the kidneys of mice, and then showed that when these mice were given MGP, the levels of NO increased in the kidneys but not in other organs. This result confirms that the cell-based delivery system provides spatial and temporal control of the production of NO. These findings demonstrate a new delivery system for therapies using gas molecules, which can be controlled spatiotemporally in mice. In the future, these types of systems could be used in the clinic for long-term treatment of conditions where artificial carriers could lead to complications.
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2023
    detail.hit.zdb_id: 2687154-3
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