Corrigendum to: 'Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration'.
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ABSTRACT:
SUBMITTER: Hu P
PROVIDER: S-EPMC7175761 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Corrigendum to: 'Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration'.
Hu Peng P Yang Qinxin Q Wang Qi Q Shi Chenshuo C Wang Dali D Armato Ubaldo U Prà Ilaria Dal ID Chiarini Anna A
Burns & trauma 20200123
[This corrects the article DOI: 10.1186/s41038-019-0178-8.]. ...[more]
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Project description:OBJECTIVES:Skin serves as the major interface between the external environment and body which is liable to many kinds of injuries. Mesenchymal stem cell (MSC) therapy has been widely used and became a promising strategy. Pre-treatment with chemical agents, hypoxia or gene modifications can partially protect MSCs against injury, and the pre-treated MSCs show the improved differentiation, homing capacity, survival and paracrine effects regard to attenuating injury. The aim of this study was to investigate whether the exosomes from the educated MSCs contribute to accelerate wound healing process. MATERIALS AND METHODS:We extracted the exosomes from the two educated MSCs and utilized them in the cutaneous wound healing model. The pro-angiogenetic effect of exosomes on endothelial cells was also investigated. RESULTS:We firstly found that MSCs pre-treated by exosomes from neonatal serum significantly improved their biological functions and the effect of therapy. Moreover, we extracted the exosomes from the educated MSCs and utilized them to treat the cutaneous wound model directly. We found that the released exosomes from MSCs which educated by neonatal serum before had the more outstanding performance in therapeutic effect. Mechanistically, we revealed that the recipient endothelial cells (ECs) were targeted and the exosomes promoted their functions to enhance angiogenesis via regulating AKT/eNOS pathway. CONCLUSIONS:Our findings unravelled the positive effect of the upgraded exosomes from the educated MSCs as a promising cell-free therapeutic strategy for cutaneous wound healing.
| S-EPMC7445410 | biostudies-literature
Project description:Human mesenchymal stromal cells (hMSCs) are a promising source for engineered cell-based therapies in which genetic engineering could enhance therapeutic efficacy and install novel cellular functions. Here, we describe an optimized Cas9-AAV6-based genome editing tool platform for site-specific mutagenesis and integration of up to more than 3 kilobases of exogenous DNA in the genome of hMSCs derived from the bone marrow, adipose tissue, and umbilical cord blood without altering their ex vivo characteristics. We generate safe harbor-integrated lines of engineered hMSCs and show that engineered luciferase-expressing hMSCs are transiently active in vivo in wound beds of db/db mice. Moreover, we generate PDGF-BB- and VEGFA-hypersecreting hMSC lines as short-term, local wound healing agents with superior therapeutic efficacy over wildtype hMSCs in the diabetic mouse model without replacing resident cells long-term. This study establishes a precise genetic engineering platform for genetic studies of hMSCs and development of engineered hMSC-based therapies.
| S-EPMC7235221 | biostudies-literature
Project description:BackgroundCutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing.MethodshADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis.ResultsCombined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha.ConclusionOur findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.
| S-EPMC8088044 | biostudies-literature
Project description:Mesenchymal stromal/stem cells (MSCs) and their secreted factors have been shown to have immunomodulatory and regenerative effects. In this study, we investigated human bone-marrow-derived MSC secretome (MSC-S) for the treatment of corneal epithelial wounds. Specifically, we evaluated the role of MSC extracellular vesicles (EV)/exosomes in mediating the wound-healing effects of the MSC-S. In vitro studies using human corneal epithelial cells showed that MSC-CM increased cell proliferation in HCEC and HCLE cells, while EV-depleted MSC-CM showed lower cell proliferation in both cell lines compared to the MSC-CM group. In vitro and in vivo experiments revealed that 1X MSC-S consistently promoted wound healing more effectively than 0.5X MSC-S, and MSC-CM promoted wound healing in a dose-dependent manner, while exosome deprivation delayed wound healing. We further evaluated the incubation period of MSC-CM on corneal wound healing and showed that MSC-S collected for 72 h is more effective than MSC-S collected for 48 h. Finally, we evaluated the stability of MSC-S under different storage conditions and found that after one cycle of freeze-thawing, MSC-S is stable at 4 °C for up to 4 weeks. Collectively, we identified the following: (i) MSC-EV/Exo as the active ingredient in MSC-S that mediates the wound-healing effects in the corneal epithelium, providing a measure to optimize its dosing for a potential clinical product; (ii) Treatment with EV/Exo-containing MSC-S resulted in an improved corneal barrier and decreased corneal haze/edema relative to EV/Exo-depleted MSC-S; (iii) The stability of MSC-CM for up to 4 weeks showed that the regular storage condition did not significantly impact its stability and therapeutic functions.
| S-EPMC10221647 | biostudies-literature
Project description:The cellular events that contribute to tissue healing of non-sterile wounds to the skin and ischaemic injury to internal organs such as the heart share remarkable similarities despite the differences between these injury types and organs. In adult vertebrates, both injuries are characterised by a complex series of overlapping events involving multiple different cell types and cellular interactions. In adult mammals both tissue-healing processes ultimately lead to the permanent formation of a fibrotic, collagenous scar, which can have varying effects on tissue function depending on the site and magnitude of damage. Extensive scarring in the heart as a result of a severe myocardial infarction contributes to ventricular dysfunction and the progression of heart failure. Some vertebrates such as adult zebrafish, however, retain a more embryonic capacity for scar-free tissue regeneration in many tissues including the skin and heart. In this review, the similarities and differences between these different types of wound healing are discussed, with special attention on recent advances in regenerative, non-scarring vertebrate models such as the zebrafish.
| S-EPMC6220283 | biostudies-literature
Project description:BACKGROUND:Cutaneous wound healing represents a morphogenetic response to injury and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cell-derived exosomes (hBM-MSC-Ex) are a promising source for cell-free therapy and skin regeneration. METHODS:In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSC-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSC-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSC-Ex on cutaneous wound healing in vivo. RESULTS:The results demonstrated that hBM-MSC-Ex promote both two types of skin cells' growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSC-Ex significantly downregulated TGF-?1, Smad2, Smad3, and Smad4 expression, while upregulated TGF-?3 and Smad7 expression in the TGF-?/Smad signaling pathway. CONCLUSIONS:Our findings indicated that hBM-MSC-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-?/Smad signal pathway. The current results provided a new sight for the therapeutic strategy for the treatment of cutaneous wounds.
| S-EPMC7245763 | biostudies-literature
Project description:The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.
| S-EPMC6525840 | biostudies-literature
Project description:Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.
| S-EPMC9791572 | biostudies-literature
Project description:BackgroundCell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing.MethodsMesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics.ResultsPHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p < 0.05). Human umbilical vein endothelial cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p < 0.05). Wounds treated with PHD-2 knockdown mesenchymal stromal cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p < 0.05). Histologic studies revealed increased blood vessel density and increased cellularity in the wounds treated with PHD-2 knockdown mesenchymal stromal cells (p < 0.05).ConclusionsSilencing PHD-2 in mesenchymal stromal cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family transcription factors and up-regulation of multiple downstream angiogenic factors.
| S-EPMC5747314 | biostudies-literature
Project description:BackgroundWound healing of skin is a complicated process. Cutaneous innervation and neurotrophic factors could participate in multiple stages of wound healing. Neurotrophic factors are mainly produced and released by neurons and neural stem cells (NSCs) which could be obtained in large quantities from human-induced pluripotent stem cells (iPSCs) in vitro. However, the potential wound healing effects of NSC secretions, such as exosomes, are unexplored yet.MethodsNSCs-derived exosomes (NSC-exo) and iPSCs-derived exosomes (iPSC-exo) were isolated from the cell culture supernatants by centrifugation, and then quantified and characterized. The effects of these exosomes on the migration of human dermal fibroblasts (HDF) cells and the tube formation of human umbilical vein endothelial cells (HUVECs) were investigated in vitro. And the in vivo wound healing effect of these exosomes were tested on the mouse skin trauma model. Therefore, a dipeptide/hyaluronic acid (Nap-FF/HA) composite hydrogel was used to encapsulate the exosomes as a sustained release carrier. Histological observations were performed to evaluate the wound healing effect of exosomes. Furthermore, the non-labeling proteomic analysis was performed to explore the possible mechanisms of NSC-exo on wound healing.ResultsWe obtained extracellular vesicles in a bowl-like structure with membranes which meet the general standards of exosomes. NSC-exo showed promotion effect on the migration of HDF cells and the tube formation of HUVECs in vitro. In a mouse skin injury model, NSC-exo enhanced the wound healing and the Nap-FF/HA hydrogel that contained exosomes did so with less drug frequency by sustaining release of exosomes. Further proteomic analysis demonstrated that the carried neurotrophic factors and immunity-related proteins in NSC-exo may play a functional role in wound healing.ConclusionNSC-exo may enhance wound healing via neurotrophic factors and immunomodulation.
| S-EPMC9733565 | biostudies-literature