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1.
Int J Mol Sci ; 22(23)2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34884554

RESUMEN

Osteoporosis is the chronic metabolic bone disease caused by the disturbance of bone remodeling due to the imbalance of osteogenesis and osteoclastogenesis. A large population suffers from osteoporosis, and most of them are postmenopausal women or older people. To date, bisphosphonates are the main therapeutic agents in the treatment of osteoporosis. However, limited therapeutic effects with diverse side effects caused by bisphosphonates hindered the therapeutic applications and decreased the quality of life. Therefore, an alternative therapy for osteoporosis is still needed. Stem cells, especially mesenchymal stem cells, have been shown as a promising medication for numerous human diseases including many refractory diseases. Recently, researchers found that the extracellular vesicles derived from these stem cells possessed the similar therapeutic potential to that of parental cells. To date, a number of studies demonstrated the therapeutic applications of exogenous MSC-EVs for the treatment of osteoporosis. In this article, we reviewed the basic back ground of EVs, the cargo and therapeutic potential of MSC-EVs, and strategies of engineering of MSC-EVs for osteoporosis treatment.


Asunto(s)
Vesículas Extracelulares/trasplante , Células Madre Mesenquimatosas/citología , Osteoporosis/terapia , Animales , Diferenciación Celular , Humanos
2.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-34202940

RESUMEN

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.


Asunto(s)
Terapia Biológica , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Enfermedades Renales/terapia , Células Madre Mesenquimatosas/metabolismo , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/terapia , Animales , Apoptosis/efectos de los fármacos , Terapia Biológica/métodos , Diferenciación Celular , Proliferación Celular/efectos de los fármacos , Autorrenovación de las Células , Fraccionamiento Químico , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Exosomas/metabolismo , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/patología , Células Madre Mesenquimatosas/citología , Sustancias Protectoras , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/etiología , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia
3.
Sci Rep ; 11(1): 14773, 2021 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-34285262

RESUMEN

As a key component of the cell-to-cell communication, small extracellular vesicles (SEVs) released from various sources are known to be affecting the physiological conditions of the target cells. Although it has been suggested that edible plant-derived nanoparticles contributes to the cross kingdom communication with the mammalian cells, the effect of these particles on cancer cell progression still needs a further exploration. Here, we isolated and then characterized garlic derived SEVs by nanoparticle tracking analysis, electron microscopy and SEV surface antibodies. In order to investigate anti-cancer property of garlic SEVs A498 human kidney carcinoma, A549 human lung carcinoma were used as cell models along with the normal human dermal fibroblast cell lines. Annexin V/pI staining and analysis of apoptotic mRNA and protein expression levels suggested that garlic SEVs induced apoptosis through activation of intrinsic pathway. Furthermore, angiogenic VEGF protein expression levels significantly decreased in response to SEVs treatment in cancer cells. Our results support that garlic derived SEVs could cause apoptotic cell death among cancer cells while normal cells remain unaffected with the treatment. This study revealed for the first time that plant SEVs possess anti-cancer affects by inducing caspase mediated apoptosis and provided a new alternative for cancer treatment.


Asunto(s)
Carcinoma de Células Renales/genética , Caspasas/genética , Vesículas Extracelulares/trasplante , Ajo/química , Neoplasias Renales/genética , Neoplasias Pulmonares/genética , Células A549 , Apoptosis , Carcinoma de Células Renales/metabolismo , Caspasas/metabolismo , Comunicación Celular , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Neoplasias Pulmonares/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
4.
Front Immunol ; 12: 811471, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35058938

RESUMEN

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.


Asunto(s)
Terapia Biológica/métodos , Vesículas Extracelulares/trasplante , Infecciones por VIH/terapia , Infecciones por VIH/virología , VIH-1 , Transporte Biológico , Comunicación Celular , Manejo de la Enfermedad , Vesículas Extracelulares/metabolismo , Regulación de la Expresión Génica , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Activación Viral/inmunología , Latencia del Virus/genética , Latencia del Virus/inmunología , Replicación Viral
5.
Physiol Rep ; 7(14): e14172, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31325249

RESUMEN

Treatment modalities for kidney disease caused by long-term exposure to heavy metals, such as cadmium (Cd), are limited. Often, chronic, long-term environmental exposure to heavy metal is not recognized in the early stages; therefore, chelation therapy is not an effective option. Extracellular vesicles (EVs) derived from stem cells have been demonstrated to reduce disease pathology in both acute and chronic kidney disease models. To test the ability of EVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) to treat Cd damage, we generated a Cd-exposed medaka model. This model develops heavy metal-induced cell damage in various organs and tissues, and shows decreased overall survival. Intravenous injection of highly purified EVs from hBM-MSCs repaired the damage to apical and basolateral membranes and mitochondria of kidney proximal tubules, glomerular podocytes, bone deformation, and improved survival. Our system also serves as a model with which to study age- and sex-dependent cell injuries of organs caused by various agents and diseases. The beneficial effects of EVs on the tissue repair process, as shown in our novel Cd-exposed medaka model, may open new broad avenues for interventional strategies.


Asunto(s)
Intoxicación por Cadmio/terapia , Vesículas Extracelulares/trasplante , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Células de la Médula Ósea/metabolismo , Intoxicación por Cadmio/metabolismo , Células Cultivadas , Vesículas Extracelulares/metabolismo , Humanos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/metabolismo , Mitocondrias/patología , Oryzias , Podocitos/metabolismo , Podocitos/patología
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