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

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bin Zhao ◽  
Xiaodong Li ◽  
Xiaomin Shi ◽  
Xueqin Shi ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Cell Communication ◽  
Rnase A ◽  
Proteinase K ◽  
Amniotic Epithelial Cells ◽  
Human Amniotic Epithelial Cells ◽  
And Migration ◽  
Proliferation And Migration

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.

scholarly journals PTH Derivative Promotes Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

2020 ◽  
Author(s):  
Yi-Fan Shen ◽  
Jing-Huan Huang ◽  
Kai-Yang Wang ◽  
Jin Zheng ◽  
Lin Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intercellular Communication ◽  
Indirect Effects ◽  
Clinical Problem ◽  
Therapeutic Effects ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing. Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities. Key words PTH, multifunctional factor, diabetic wound, exosomes, synergistic effect

scholarly journals PTH Derivative Promotes Chronic Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

2019 ◽  
Author(s):  
Yi-Fan Shen ◽  
Jing-Huan Huang ◽  
Kai-Yang Wang ◽  
Jin Zheng ◽  
Lin Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intercellular Communication ◽  
Indirect Effects ◽  
Chronic Wound ◽  
Therapeutic Effects ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Chronic diabetic wounds are a disturbing and rapidly growing clinical problem. Parathyroid hormone related peptide (PTHrP-2) was assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in chronic wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 was determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 was determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos was added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played hub role in PTHrP-2 indirect effects in wound healing. Conclusion: The findings of this study indicate that PTHrP-2, a multifunctional factor, can promote chronic wound healing via synergistic multicellular stimulating and exosomal activities.

PTH Derivative Promotes Chronic Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

2020 ◽  
Author(s):  
Yi-Fan Shen ◽  
Jing-Huan Huang ◽  
Kai-Yang Wang ◽  
Jin Zheng ◽  
Lin Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intercellular Communication ◽  
Indirect Effects ◽  
Chronic Wound ◽  
Therapeutic Effects ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Chronic diabetic wounds are a disturbing and rapidly growing clinical problem. Parathyroid hormone related peptide (PTHrP-2) was assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in chronic wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 was determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 was determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos was added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played hub role in PTHrP-2 indirect effects in wound healing. Conclusion: The findings of this study indicate that PTHrP-2, a multifunctional factor, can promote chronic wound healing via synergistic multicellular stimulating and exosomal activities.

scholarly journals Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1595 ◽  
Author(s):  
Sungjoo Park ◽  
Eunsu Ko ◽  
Jun Hyoung Lee ◽  
Yoseb Song ◽  
Chang-Hao Cui ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Connective Tissue ◽  
Wound Closure ◽  
Tissue Growth ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
And Migration ◽  
Proliferation And Migration

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

scholarly journals Producing Human Amniotic Epithelial Cells-only Membrane for Transplantation

2019 ◽  
Author(s):  
Chenze Xu ◽  
Waqas Ahmed ◽  
Lili Xie ◽  
Yan Peng ◽  
Qizheng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Epithelial Cells ◽  
Human Amniotic Membrane ◽  
Transcriptional Level ◽  
Type I ◽  
Amniotic Epithelial Cells ◽  
Human Amniotic Epithelial Cells ◽  
Conventional Methods ◽  
Clinical Potential

AbstractHuman amniotic epithelial cells (hAECs), as pluripotent stem cells, have characteristics of immune privilege and great clinical potential. Here, we produced hAECs membrane consisting of single-layer hAECs and basal membrane (BM) of human amniotic membrane (hAM). In conventional methods, hAECs were isolated from hAM by repeated trypsin digestion. In this study, collagenase I and cell scraper were used to remove human amniotic mesenchymal stem cells (hAMSCs) from hAM and hAECs-only membranes were produced. These hAECs on the membranes were evaluated by surface biomarkers including epithelial cell adhesion molecule (EpCAM), stage-specific embryonic antigen 4 (SSEA4) and endoglin (CD105), transcriptional level of biomarkers including POU class 5 homeobox 1 (OCT4), sex determining region Y-box 2 (SOX2), fibroblast growth factor 4 (FGF4), immunofluorescence of cytokeratin-8 (CK-8), alpha smooth muscle actin (α-SMA) and collagen type I alpha 1 chain (ColA1). Finally, the hAECs membrane were transplanted on skin-removed mice to evaluate its effect on wound healing. In comparison to the hAECs isolated by the conventional methods, the cells isolated by this proposed method had higher purity of hAECs, expressed higher in pluripotency related genes, and maintained an epithelium construction in a long-term culture. In mice application, the hAECs membrane effectively improved the skin wound healing. An efficient method was successfully established to produce hAECs membrane in this work which not only held promise to obtain hAECs in higher purity and quality, but also showed practical clinical potential.

Hepatic differentiation of human amniotic epithelial cells and in vivo therapeutic effect on animal model of cirrhosis

2015 ◽  
Vol 30 (11) ◽  
pp. 1673-1682 ◽  
Author(s):  
Jaymie Siqi Lin ◽  
Lei Zhou ◽  
Antony Sagayaraj ◽  
Nur Halisah Bte Jumat ◽  
Mahesh Choolani ◽  
...  
Keyword(s):  
Animal Model ◽  
Epithelial Cells ◽  
Therapeutic Effect ◽  
Hepatic Differentiation ◽  
Amniotic Epithelial Cells ◽  
Human Amniotic Epithelial Cells

scholarly journals Puerarin Improves Dexamethasone-Impaired Wound Healing In Vitro and In Vivo by Enhancing Keratinocyte Proliferation and Migration

2021 ◽  
Vol 11 (19) ◽  
pp. 9343
Author(s):  
Ly Thi Huong Nguyen ◽  
Sang-Hyun Ahn ◽  
Min-Jin Choi ◽  
In-Jun Yang ◽  
Heung-Mook Shin
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Hacat Cells ◽  
Impaired Wound Healing ◽  
Keratinocyte Proliferation ◽  
And Migration ◽  
Proliferation And Migration

The delayed and impaired wound healing caused by dexamethasone (DEX) is commonly reported. Puerarin, the major isoflavone found in Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep promoted the wound healing process in diabetic rats. However, the effects and underlying mechanisms of puerarin on DEX-impaired wound healing have not been investigated. This study examined the potential uses of puerarin in upregulating keratinocyte proliferation and migration in dexamethasone (DEX)-suppressed wound healing model. The effects of puerarin on wound healing in vivo were investigated by taking full-thickness 5 mm punch biopsies from the dorsal skin of BALB/c mice and then treating them topically with 0.1% DEX. For the in vitro study, DEX-treated HaCaT cells were used to examine the effects of puerarin on DEX-induced keratinocyte proliferation and migration and the mechanisms of its action. Puerarin, when applied topically, accelerated the wound closure rate, increased the density of the capillaries, and upregulated the level of collagen fibers and TGF-β in the wound sites compared to the DEX-treated mice. Puerarin promoted the proliferation and migration of keratinocytes by activating the ERK and Akt signaling pathways in DEX-treated HaCaT cells. In conclusion, puerarin could be effective in reversing delayed and disrupted wound healing associated with DEX treatments.

scholarly journals A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

scholarly journals Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Li ◽  
Jian Zhang ◽  
Jihong Shi ◽  
Kaituo Liu ◽  
Xujie Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Hypertrophic Scar ◽  
Treated Group ◽  
Smad Pathway ◽  
In Vivo Experiments ◽  
Immunohistochemistry Staining ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Hypertrophic scar (HS) is a fibro-proliferative disorder of dermis after burn or trauma and usually leads to esthetic disfiguration and functionary impairment for patients. Emerging evidences demonstrated ADSC-Exo could alleviate the visceral fibrosis, but little attention had been paid to its role in skin fibrosis. In the study, we would explore the effect of ADSC-Exo on HS and investigated the exact mechanism underlying the properties. Methods ADSC-Exo were isolated, identified, and internalized by HS-derived fibroblasts (HSFs). The effect of ADSC-Exo on the proliferation and migration of HSFs were detected by flow cytometry and Ki67 immunofluorescence staining, or scratch and trans-wells assays, respectively. RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry staining were used to evaluate the expression of IL-17RA, Col1, Col3, α-SMA, SIP1, and p-Smad2/p-Smad3 in HSFs stimulated with ADSC-Exo, miR-192-5p mimics, or inhibitors, IL-17RA siRNA and their negative controls. Digital morphology, H&E, Masson’s trichrome staining, and immunohistochemistry staining were performed to measure the effect of ADSC-Exo and Lv-IL-17RA shRNA on excisional wound of BALB/c mice. Results The verified ADSC-Exo effectively inhibited the proliferation and migration of HSFs, decreased the expression of Col1, Col3, α-SMA, IL-17RA, and p-Smad2/p-Smad3 and increased the levels of SIP1 in HSFs. Besides, the mice in ADSC-Exo-treated group demonstrated faster wound healing and less collagen deposition. Furthermore, miR-192-5p was highly expressed in ADSC-Exo and ADSC-Exosomal miR-192-5p ameliorated hypertrophic scar fibrosis. Meanwhile, miR-192-5p targeted the expression of IL-17RA to decrease the pro-fibrotic proteins levels. Moreover, IL-17RA was overexpressed in HS and HSFs, and knockdown IL-17RA alleviated the expression of Col1, Col3, α-SMA, and p-Smad2/p-Smad3 and increased the expression of SIP1 in HSFs. Most importantly, IL-17RA silence also facilitated wound healing, attenuated collagen production, and modulated Smad pathway in HSFs. Conclusions This study illustrated ADSC-Exo attenuated the deposition of collagen, the trans-differentiation of fibroblasts-to-myofibroblasts, and the formation of hypertrophic scar by in vitro and in vivo experiments. ADSC-Exosomal miR-192-5p targeted IL-17RA to regulate Smad pathway in hypertrophic scar fibrosis. ADSC-Exo could be a promising therapeutic strategy for clinical treatment of hypertrophic scar and the anti-fibrotic properties could be achieved by miR-192-5p/IL-17RA/Smad axis.

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