Stem Cell–Mediated Paracrine Signaling Alters Fibroplasia in Human Vocal Fold Fibroblasts in Vitro

Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C.

doi:10.1177/0003489417716186

Cited by 13 publications

(20 citation statements)

References 37 publications

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“…hAECs, which can be obtained from the discarded amnion tissue via noninvasive procedure, have emerged as an alternative resource for stem cell therapy [ 22 ]. It was reported that the reparative effect of stem cells was mediated by paracrine signaling with the release of biologically active molecules affecting cell migration and/or proliferation [ 23 ]. In particular, the exosomes, an essential paracrine factor secreted by many cell types, played a dominant role in the regulation of tissue repair and regeneration [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts

Zhao

Shi

et al. 2018

Stem Cells International

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Previous work in our laboratory demonstrated that exosomes derived from human amniotic epithelial cells (hAECs) accelerated wound healing by promoting the proliferation and migration of fibroblasts. It is reported that exosomes, which are carriers of the microRNAs (miRNAs) and proteins, play an important role in the regulation of cell-to-cell communication. However, it is still unclear precisely which molecule or which group of molecules carried within hAEC-derived exosomes (hAEC-Exos) mediated wound healing. Here, we explored purified hAEC-Exos together with either proteinase K (PROse) or RNase A on the effect of fibroblasts and cutaneous wound healing. Our experiments demonstrated that hAEC-Exos were positive for exosomal markers CD9, CD63, and CD81. Also, we found that hAEC-Exos could be internalized by fibroblasts and then stimulated cell migration and proliferation. However, the promotive effect of hAEC-Exos was abolished by pretreating hAEC-Exos with RNase A, not PROse. Importantly, in vivo wound healing assay showed that local injection of hAEC-Exos or PROse pretreated hAEC-Exos at skin wounds significantly accelerated wound healing. Our findings revealed an important role of exosomal miRNAs in wound healing.

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Section: Discussionmentioning

confidence: 99%

Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts

Zhao

Shi

et al. 2018

Stem Cells International

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“…Hiwatashi et al . () demonstrated in vitro the inhibiting effects of the medium in which bone marrow‐derived MSC were cultured on the secretion of transforming growth factor‐β1 by human vocal fold fibroblasts. In the experiments in vivo , 1 month postimplantation the overwhelming majority of the vocal fold‐implanted MSC were proven dead, no long‐term engraftment was observed, that also indicated the realisation of the stem cell regenerative potential via paracrine mechanisms (Hertegård et al ., ; Bartlett et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…According to the review (Vizoso et al, 2017), the secreted wide spectrum of anti-inflammatory mediators and cytokines, as well as different growth factors, has a greater significance in wound healing than direct proliferation of stem cells at the site of their implantation. Hiwatashi et al (2017) demonstrated in vitro the inhibiting effects of the medium in which bone marrow-derived MSC were cultured on the secretion of transforming growth factor-β1 by human vocal fold fibroblasts. In the experiments in vivo, 1 month postimplantation the overwhelming majority of the vocal fold-implanted MSC were proven dead, no long-term engraftment was observed, that also indicated the realisation of the stem cell regenerative potential via paracrine mechanisms (Hertegård et al, 2006;Bartlett et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In a number of studies (Hertegård et al, 2006;Hiwatashi et al, 2017;Vizoso et al, 2017), dedicated to the effect of stem cells on the processes of vocal fold scarring after damage, a point estimation of the general level of fibrosis, density of collagen fibres is applied for the assessment of the fibrosis level, however, all the other morphological components are not taken into account. In this connection, in our study we used a semiquantitative analysis by 11 criteria with the subsequent statistical processing, to objectively demonstrate the differences between the scars formed without treatment and those formed in the MSC presence.…”

Section: Discussionmentioning

confidence: 99%

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Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study

Свистушкин

Kotova

Shekhter

et al. 2019

Journal of Microscopy

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Summary Regenerative medicine opens new opportunities in the repair of cicatricial lesions of the vocal folds. Here, we present a thorough morphological study, with the focus on the collagen structures in the mucosa of the vocal folds, dedicated to the effects of stem cells on the vocal folds repair after cicatricial lesions. We used a conventional experimental model of a mature scar of the rabbit vocal folds, which was surgically excised with a simultaneous implantation of autologous bone marrow‐derived mesenchymal stem cells (MSC) into the defect. The restoration of the vocal folds was studied 3 months postimplantation of stem cells and 6 months after the first surgery. The collagen structure assessment included histology, immunohistochemistry and atomic force microscopy (AFM) studies. According to the data of optical microscopy and AFM, as well as to immunohistochemical analysis, MSC implantation into the vocal fold defect leads not only to the general reduction of scarring, normal ratio of collagens type I and type III, but also to a more complete restoration of architecture and ultrastructure of collagen fibres in the mucosa, as compared to the control. The collagen structures in the scar tissue in the vocal folds with implanted MSC are more similar to those in the normal mucosa of the vocal folds than to those of the untreated scars. AFM has proven to be an instrumental technique in the assessment of the ultrastructure restoration in such studies. Lay Description Regenerative medicine opens new opportunities in the repair of the vocal fold scars. Because collagen is a main component in the vocal fold mucosa responsible for the scar formation and repair, we focus on the collagen structures in the mucosa of the vocal folds, using a thorough morphological study based on histology and atomic force microscopy (AFM). Atomic force microscopy is a scanning microscopic technique which allows revealing the internal structure of a tissue with a resolution up to nanometres. We used a conventional experimental model of a mature scar of the rabbit vocal folds, surgically excised and treated with a mesenchymal stem cells transplant. Our morphological study, primarily AFM, explicitly shows that the collagen structures in the scarred vocal folds almost completely restore after the stem cell treatment. Thus, the modern microscopic methods, and especially AFM are instrumental tools for monitoring the repair of the vocal folds scars.

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“…Human amnion mesenchymal stem cells (hAMSCs) are obtained by surgery from human amniotic tissue and are now often used as an alternative resource for stem cell therapy [13]. According to research reports, stem cells exert repair effects through paracrine signaling and affect cell proliferation and migration through the release of bioactive factors [14]. Exosomes are important paracrine factors secreted by numerous cell types, and current studies have found that they play a dominant role in tissue repair and regeneration [15].…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression

et al. 2020

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Background: Wound healing is a complex pathophysiological process that involves a variety of cells and cytokines. In this study, we found that local injection of human amnion mesenchymal stem cells into wounds in rats could promote wound healing. Therefore, we hypothesized that the exosomes of human amnion mesenchymal stem cells contain substances that regulate the migration of epidermal cells. It has been reported that miR-135a is involved in cell migration and transformation. However, there have been no reports of its function in skin wound healing. Methods: To test this hypothesis, we injected exosomes overexpressing miR-135a directly into the wound margin. In addition, we tested the migration of BJ cells with overexpression or knockdown of miR-135a in vitro. Additionally, Western blot analysis was used to detect the expression of fibroblast migration-associated proteins after treatment with miR-135a overexpression or knockdown. Results: MiR-135a significantly promoted wound healing compared to the control treatment. Western blot analysis showed a significant downregulation of LATS2 after overexpression of miR-135a. In addition, knockdown of miR-135a effectively attenuated the promoting effect of exosomes on cell migration. Conclusions: Our results indicated that miR-135a promotes wound healing, which may be mediated by downregulating LATS2 levels to increase cell migration. This study provides a rationale for the therapeutic effect on wound healing of miR-135a in exosomes derived from human amnion mesenchymal stem cells.

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Stem Cell–Mediated Paracrine Signaling Alters Fibroplasia in Human Vocal Fold Fibroblasts in Vitro

Abstract: Conditioned media affected many profibrotic cell activities in TGF-β1-stimulated VFFs, likely related to altered TGF-β signaling. These data provide preliminary insight regarding the antifibrotic effects of MSCs and further support their progression to clinical utility.

Cited by 13 publications

References 37 publications

Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts

Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts

Collagen fibrillar structures in vocal fold scarring and repair using stem cell therapy: a detailed histological, immunohistochemical and atomic force microscopy study

Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression

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