Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sushmitha Sriramulu ◽  
Antara Banerjee ◽  
Ganesan Jothimani ◽  
Surajit Pathak
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Human Keratinocytes ◽  
Human Umbilical Cord ◽  
Hacat Cells ◽  
And Migration

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo

2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
And Migration

scholarly journals Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Psoriasis-like Skin Inflammation

2020 ◽  
Author(s):  
Yuli Zhang ◽  
Jianjun Yan ◽  
Zhengjun Li ◽  
Qing Sun
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Western Blotting ◽  
Skin Diseases ◽  
Skin Inflammation ◽  
Human Umbilical Cord ◽  
Hacat Cells ◽  
Inflammatory Skin Diseases

Abstract Background Exosomes are nanovesicles secreted from endosomal membranes. The immunomodulatory effect of mesenchymal stem cells (MSCs) is mediated by MSCs-derived exosomes (MSCs-exo). MSCs-exo are attractive candidates for use in cell therapy for several inflammatory diseases including psoriasis. We investigated whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-Exo) ameliorate psoriasis-like skin inflammation via the IL-23/IL-17 axis. Methods HucMSCs-Exo were isolated by differential ultracentrifugation. Imiquimod (IMQ)-induced mice were subcutaneously injected with hucMSCs-Exo on days 0, 2 and 4. H&E staining and Western blotting were performed, and tissue histopathology and STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels were assessed. HucMSCs-Exo were co-cultured with dendritic cells (DCs) and HaCat cells in vitro. Western blotting, flow cytometry and ELISAs were then performed to measure STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels. Results Subcutaneous injection of hucMSCs-Exo significantly ameliorated symptoms and diminished the clinical and pathological scores of psoriasis in IMQ-induced mice. In MSCs-exo-treated mice, STAT3/p-STAT3, IL-17, IL-23 and CCL20 levels were decreased. HucMSCs-Exo co-cultured in vitro with DCs suppressed DC maturation and activation and inhibited IL-23 secretion. HucMSCs-Exo co-cultured with HaCat cells reduced STAT3/p-STAT3, IL-17, IL-23, and CCL20 levels. Conclusions HucMSCs-Exo can effectively ameliorate psoriasis-like skin inflammation in mice via the IL-23/IL-17 axis. Furthermore, hucMSCs-Exo exhibit immunomodulatory potency by inhibiting the maturation and activation of DCs and blocking the positive feedback effect of IL-17 on keratinocytes. Our data offer a novel therapeutic approach for chronic inflammatory skin diseases such as psoriasis by leveraging the immunomodulatory effects of hucMSCs-Exo.

scholarly journals Microvesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Alveolar Development and Attenuate Lung Inflammation in a Rat Model of Bronchopulmonary Dysplasia Induced by Antenatal Lipopolysaccharide

2021 ◽  
Author(s):  
Ou Zhou ◽  
Jingyi You ◽  
Xiaochuan Xu ◽  
Jiang Liu ◽  
Huijun Qiu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Lung Function ◽  
Umbilical Cord ◽  
Rat Model ◽  
Lung Inflammation ◽  
Human Umbilical Cord ◽  
Alveolar Development ◽  
And Function

Abstract BackgroundAlthough it is known that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate hyperoxic lung injury of bronchopulmonary dysplasia (BPD) in animal models, the role of microvesicles (MVs) derived from hUCMSCs in BPD is poorly defined. Furthermore, antenatal inflammation has been linked to high risk of BPD in preterm infants. The purpose of this study was to explore whether MVs derived from hUCMSCs can preserve lung structure and function in an antenatal lipopolysaccharide (LPS)-induced BPD rat model and to clarify the underlying mechanism.MethodsPregnant rats received intra-amniotic injections of LPS on day 20.5 of gestation (term=day 22.5 of gestion), and pups were delivered by cesarean section on embryonic day 22.5 (E22.5). MVs were isolated by ultracentrifugation and then were characterized. hUCMSCs and MVs were administered intratracheally on postnatal day 7 (PN7). On PN14, lung function was measured, and tissues were harvested to determine alveolarization. Immunofluorescence staining was used to determine the co-localization of MVs and lung cells. Cell proliferation was measured by Ki-67 staining, and apoptosis was determined by flow cytometry using 7-ADD and Annexin V. The expression levels of AKT, p38, JNK, ERK, and their phosphorylated forms, PTEN and VEGF, were measured by WB.ResultsAntenatal LPS induced alveolar simplification, altered lung function, and dysregulated pulmonary vasculature. Both hUCMSCs and MVs successfully promoted alveolar development and improved lung function. However, hUCMSCs but not MVs restored the loss of pulmonary microvascular vessels (<100 μm). Furthermore, MVs were mostly uptaken by alveolar epithelial type II cells (AT2) and macrophages. Compared with the LPS-exposed group, MVs restored the AT2 cell number and SP-C expression in vivo and promoted the proliferation of AT2 cells in vitro. MVs also restored the level of IL-6 and IL-10 in lung homogenate. Additionally, upregulated expression of p-AKT, downregulated expression of PTEN, as well as inhibition of MAPK pathway were observed in MVs-treated BPD rats.ConclusionsMVs derived from hUCMSCs improve lung architecture and function in an antenatal LPS-induced BPD rat model by promoting AT2 cell proliferation and attenuate lung inflammation; thus, MVs provide a promising therapeutic vehicle for BPD treatment.

Autophagy of umbilical cord mesenchymal stem cells conduces to pro-angiogenic function of conditioned medium

2021 ◽  
Author(s):  
Wenya Wang ◽  
Xiao Li ◽  
Chaochu Cui ◽  
Dongling Liu ◽  
Guotian Yin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Umbilical Cord ◽  
Tube Formation ◽  
Dependent Manner ◽  
And Control

Abstract BackgroundAngiogenesis is a key prerequisite for wound healing. The conditioned medium following culture of umbilical cord mesenchymal stem cells (UCMSCs) has a potential to promote angiogenesis, but the efficacy is very low. Autophagy is an important process in protein recycling and a contributor for cell exocrine, which maybe stimulate the release of cytokines from UCMSCs to the medium and enhance the pro-angiogenic efficacy of the conditioned medium.MethodsAutophagy in UCMSCs was induced by 100 nM, 1 µM and 10 µM rapamycin for 6-hour and then detected by LC-3 immunofluorescence staining. After induction, the cells were washed with PBS for 3 times and cultured in fresh medium without rapamycin for additional 24-hour. And then, the conditioned medium was collected for the following experiments. The angiogenic effects of different groups of conditioned medium were verified by in vitro and in vivo tube formation assays in the matrigel-coated plates and matrigel plaques injected in mouse inguinal areas. Finally, the expressions of angiogenic factors including VEGF, FGF-1, FGF-2, TGF-α, MMP-3, MMP-9, PDGF-α, PDGF-β, HIF-1α and Ang II in the autophagic and control UCMSCs were measured by q-PCR assay.ResultsRapamycin induced autophagy of UCMSCs in a dose dependent manner, but the conditioned medium in 100 nM rapamycin-induced group was with the best pro-angiogenic efficacy. Thus, this group of medium was viewed as the optimal conditioned medium. The in vivo tube formation assay showed that angiogenesis in matrigel plaques injected daily with the optimal conditioned medium was more obvious than that injected with the control conditioned medium. Further, the expressions of VEGF, FGF-2, PDGF-α, MMP-9 and HIF-1α were markedly increased in UCMSCs following treatment with 100 nM rapamycin.ConclusionAppropriate autophagy improves the pro-angiogenic efficacy of the conditioned medium, which might be utilized to optimize the applications of UCMSCs-derived conditioned medium in wound healing and tissue repair.Trial registrationNot applicable.

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