Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

Jiang, Tiechao; Wang, Zhongyu; Sun, Ji

doi:10.1186/s13287-020-01723-6

Cited by 109 publications

(74 citation statements)

References 41 publications

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“…Regarding the proliferation and migration of keratinocytes and fibroblasts, we found that exosomes secreted by bone marrow-derived MSCs significantly increase both processes in these cells. These results corroborate well and extend previous reports on exosomes obtained from other sources such as adipose-tissue-derived MSCs [32][33][34] as well as bone marrow-derived MSCs [35]. It is known that in chronic wounds the cells residing in the periphery of the lesion have low proliferative and migratory capacity [36].…”

Section: Discussionsupporting

confidence: 91%

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

Ţuţuianu¹,

Rosca²,

Iacomi³

et al. 2021

IJMS

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Bone marrow-derived mesenchymal stromal cells (MSCs) are major players in regenerative therapies for wound healing via their paracrine activity, mediated partially by exosomes. Our purpose was to test if MSC-derived exosomes could accelerate wound healing by enhancing the biological properties of the main cell types involved in the key phases of this process. Thus, the effects of exosomes on (i) macrophage activation, (ii) angiogenesis, (iii) keratinocytes and dermal fibroblasts proliferation and migration, and (iv) the capacity of myofibroblasts to regulate the turnover of the extracellular matrix were evaluated. The results showed that, although exosomes did not exhibit anti-inflammatory properties, they stimulated angiogenesis. Exposure of keratinocytes and dermal (myo)fibroblasts to exosomes enhanced their proliferation and migratory capacity. Additionally, exosomes prevented the upregulation of gene expression for type I and III collagen, α-smooth muscle actin, and MMP2 and 14, and they increased MMP13 expression during the fibroblast–myofibroblast transition. The regenerative properties of exosomes were validated using a wound healing skin organotypic model, which exhibited full re-epithelialization upon exosomes exposure. In summary, these data indicate that exosomes enhance the biological properties of keratinocytes, fibroblasts, and endothelial cells, thus providing a reliable therapeutic tool for skin regeneration.

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Section: Discussionsupporting

confidence: 91%

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

Ţuţuianu¹,

Rosca²,

Iacomi³

et al. 2021

IJMS

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“…Studies have shown that stem cells in the revitalization of the tissues are closely related to the paracrine signaling of exosomes. The exosomes derived from bone marrow mesenchymal stem cell with CD63 + were reported to accelerate migration and proliferation of fibroblasts (Jiang et al, 2020; McBride et al, 2017; Yu et al, 2020), and accelerate the healing of abnormal wounds (Kim et al, 2018; Ti et al, 2016). The exosomes were found to repair the damaged tissue and promote the growth of various kinds of cells and act as an important mediator in intercellular communication (Geiger et al, 2015; Li et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Chen

Qin

Chen

et al. 2021

Cell Biology International

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Nonhealing wounds in diabetes remain a global clinical and research challenge. Exosomes are primary mediators of cell paracrine action, which are shown to promote tissue repair and regeneration. In this study, we investigated the effects of serum derived exosomes (Serum‐Exos) on diabetic wound healing and its possible mechanisms. Serum‐Exos were isolated from blood serum of normal healthy mice and identified by transmission electron microscopy and western blot. The effects of Serum‐Exos on diabetic wound healing, fibroblast growth and migration, angiogenesis and extracellular matrix (ECM) formation were investigated. Our results showed that the isolated Serum‐Exos exhibited a sphere‐shaped morphology with a mean diameter at 150 nm, and expressed classical markers of exosomes including HSP70, TSG101, and CD63. Treatment with Serum‐Exos elevated the percentage of wound closure and shortened the time of healing in diabetic mice. Mechanistically, Serum‐Exos promoted granulation tissue formation and increased the expression of CD31, fibronectin and collagen‐ɑ in diabetic mice. Serum‐Exos also promoted the migration of NIH/3T3 cells, which was associated with increased expression levels of PCNA, Ki67, collagen‐α and fibronectin. In addition, Serum‐Exos enhanced tube formation in human umbilical vein endothelial cells and induced the expression of CD31 at both protein and messenger RNA levels. Collectively, our results suggest that Serum‐Exos may facilitate the wound healing in diabetic mice by promoting angiogenesis and ECM formation, and show the potential application in treating diabetic wounds.

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“…For all of this, apart from the direct use of hMSCs, many recent preclinical studies have evaluated the use of exosomes and conditioned mediums derived from them. These released molecules, alone or combine with other substances or scaffolds, have reported successful result in terms of wound closure and re-epithalization ( Shabbir et al, 2015 ; Tao et al, 2017 ; Aryan et al, 2019 ; Dalirfardouei et al, 2019 ; Wang et al, 2019 ; Zhou et al, 2019 ; Jiang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases

Sierra-Sánchez

Montero‐Vílchez

Quiñones-Vico

et al. 2021

Front. Cell Dev. Biol.

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Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015–2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound’s size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.

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Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

Cited by 109 publications

References 41 publications

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis

Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases

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