Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury

ACS Nano, Год журнала: 2019, Номер 13(9), С. 10015 - 10028

Опубликована: Авг. 27, 2019

Individuals with spinal cord injury (SCI) usually suffer from permanent neurological deficits, while spontaneous recovery and therapeutic efficacy are limited. Here, we demonstrate that when given intranasally, exosomes derived mesenchymal stem cells (MSC-Exo) could pass the blood brain barrier migrate to injured area. Furthermore, MSC-Exo loaded phosphatase tensin homolog small interfering RNA (ExoPTEN) attenuate expression of PTEN in region following intranasal administrations. In addition, considerably enhanced axonal growth neovascularization, reducing microgliosis astrogliosis. The ExoPTEN therapy also partly improve structural electrophysiological function and, most importantly, significantly elicited functional rats complete SCI. results imply may be used clinically promote for SCI individuals.

Язык: Английский

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GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

Frontiers in Physiology, Год журнала: 2017, Номер 8

Опубликована: Ноя. 6, 2017

Background: Delayed wound healing in diabetic patients is one of the most challenging complications clinical medicine, as it poses a greater risk gangrene, amputation and even death. Therefore, novel method to promote considerable interest at present. Previous studies showed that injection MSC-derived exosomes has beneficial effects on healing. In current studies, we aimed isolate derived from gingival mesenchymal stem cells (GMSCs) then loading them chitosan/silk hydrogel sponge evaluate this non-invasive skin defects rats. Methods: GMSCs were isolated human connective tissue characterized by surface antigen analysis vitro multipotent differentiation. The cell supernatant was collected exosomes. transmission electron microscopy, Western blot size distribution analysis. chitosan/silk-based prepared using freeze-drying structural physical properties characterized. Then, added tested rat defect model. evaluated area measurement, histological, immunohistochemical immunofluorescence Results: We have successfully with mean diameter 127 nm. had appropriate swelling moisture retention capacity. vivo incorporating GMSC-derived could effectively defects. histological revealed more neo-epithelium collagen hydrogel-exosome group. addition, group highest microvessel density nerve density. Conclusions: combination rats promoting re-epithelialization, deposition remodeling enhancing angiogenesis neuronal ingrowth. These findings not only provide new information role but also application practical value for repair.

Язык: Английский

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Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo

Theranostics, Год журнала: 2019, Номер 9(14), С. 4084 - 4100

Опубликована: Янв. 1, 2019

Objectives: Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell apoptosis which to excessive endoplasmic reticulum (ER) stress in the intervertebral (IVD) could aggravate IDD progression. Many studies have shown therapeutic potential exosomes derived from bone marrow mesenchymal stem cells (MSC-exos) diseases. We hypothesized that delivery MSC-exos modulate ER inhibit NP during IDD. Methods: The levels were measured normal or tissues for contrast. effects testified advanced glycation end products (AGEs) -induced human cells. mechanism involving AKT ERK signaling pathways was investigated using RNA interference inhibitors. Histological immunohistochemical analysis TUNEL staining used evaluating vivo. Results: level apoptotic rate elevated IVD tissues. attenuate stress-induced by activating signaling. Moreover, vivo modulated stress-related retarded progression rat tail model. Conclusions: These results highlight preventing Our work first demonstrate AGEs-associated degeneration.

Язык: Английский

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Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Cell Death and Disease, Год журнала: 2022, Номер 13(7)

Опубликована: Июль 4, 2022

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal multipotent differentiation. There is compelling evidence that therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental effectors play a crucial role in intercellular communication, existing body fluids cell supernatants. Since MSC-derived EVs retain function protocells have lower immunogenicity, they wide range prospective applications advantages over therapy. We describe some characteristics MSC-EVs, discuss immune regulation regeneration, emphasis molecular mechanism application MSC-EVs treatment fibrosis support tissue repair. also highlight current challenges clinical ways to overcome problem quality heterogeneity.

Язык: Английский

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Mesenchymal Stromal/Stem Cells in Regenerative Medicine and Tissue Engineering

Stem Cells International, Год журнала: 2018, Номер 2018, С. 1 - 16

Опубликована: Авг. 19, 2018

As a result of over five decades investigation, mesenchymal stromal/stem cells (MSCs) have emerged as versatile and frequently utilized cell source in the fields regenerative medicine tissue engineering. In this review, we summarize history MSC research from initial discovery their multipotency to more recent recognition perivascular identity vivo extraordinary capacity for immunomodulation angiogenic signaling. well, discuss long-standing questions regarding developmental origins differentiation toward range lineages. We also highlight important considerations potential risks involved with isolation, ex expansion, clinical use. Overall, review aims serve an overview breadth that has demonstrated utility MSCs wide contexts continues unravel mechanisms by which these exert therapeutic effects.

Язык: Английский

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Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126

Acta Biomaterialia, Год журнала: 2019, Номер 103, С. 196 - 212

Опубликована: Дек. 17, 2019

Язык: Английский

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Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway

Experimental Cell Research, Год журнала: 2018, Номер 370(2), С. 333 - 342

Опубликована: Июнь 28, 2018

Язык: Английский

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Manufacturing of primed mesenchymal stromal cells for therapy

Nature Biomedical Engineering, Год журнала: 2019, Номер 3(2), С. 90 - 104

Опубликована: Янв. 28, 2019

Язык: Английский

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The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine

Stem Cell Research & Therapy, Год журнала: 2019, Номер 10(1)

Опубликована: Янв. 3, 2019

Menstrual blood-derived stem cells (MenSCs) are a novel source of mesenchymal (MSCs). MenSCs attracting more and attention since their discovery in 2007. also have no moral dilemma show some unique features known adult-derived cells, which provide an alternative for the research application regenerative medicine. Currently, people increasingly interested clinical potential due to high proliferation, remarkable versatility, periodic acquisition non-invasive manner with other sources MSCs that comparable adult tissue. In this review, plasticity pluripotent biological characteristics, immunophenotype function, differentiative potential, immunomodulatory properties assessed. Furthermore, we summarize therapeutic effects functional characteristics various diseases, including liver disease, diabetes, stroke, Duchenne muscular dystrophy, ovarian-related myocardial infarction, Asherman syndrome, Alzheimer's acute lung injury, cutaneous wound, endometriosis, neurodegenerative diseases. Subsequently, is investigated. There need deeper understanding its diagnostic safety concern on variety environmental conditions (such as epidemiological backgrounds, age, hormonal status, pre-contraceptive). summary, MenSC has great reducing mortality improving quality life severe patients. As kind multiple treating diseases medicine future applications.

Язык: Английский

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Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice

Theranostics, Год журнала: 2019, Номер 9(20), С. 5956 - 5975

Опубликована: Янв. 1, 2019

Mesenchymal stem cell-derived exosomes (MSC-Exo) have robust anti-inflammatory effects in the treatment of neurological diseases such as epilepsy, stroke, or traumatic brain injury. While astrocytes are thought to be mediators these effects, their precise role remains poorly understood. To address this issue, we investigated putative therapeutic and mechanism MSC-Exo on inflammation-induced alterations astrocytes. Methods: Lipopolysaccharide (LPS)-stimulated hippocampal primary culture were treated with MSC-Exo, which also administered pilocarpine-induced status epilepticus (SE) mice. Exosomal integration, reactive astrogliosis, inflammatory responses, calcium signaling, mitochondrial membrane potentials (MMP) monitored. experimentally probe molecular actions astrocytic activation, inhibited nuclear factor erythroid-derived 2, like 2 (Nrf2, a key mediator neuroinflammation oxidative stress) by sgRNA (in vitro) ML385 (Nrf2 inhibitor) vivo. Results: incorporated into well attenuated astrogliosis responses vitro Also, ameliorated LPS-induced aberrant signaling dysfunction culture, SE-induced learning memory impairments Furthermore, activation (e.g., reduced NF-κB deactivation) weakened Nrf2 inhibition. Conclusions: Our results show that ameliorate astrocyte Nrf2-NF-κB pathway is involved regulating These data suggest promising potential nanotherapeutic agent for alterations.

Язык: Английский

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