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1.
Though mesenchymal stem cells (MSCs) are considered as an important pillar of regenerative medicine, their regenerative potential has been shown to be limited in several pathological conditions. The adverse properties of MSC-based cell therapy have drawn attention to the therapeutic use of MSC-derived secretome. However, MSC-originated exosomes and microvesicles can also possess a significant impact on disease development, including cancer. By interchanging secretome, MSCs can interact with tumor cells and promote mutual exchange/induction of cellular markers. In addition, enzymes secreted into and activated within exosomes can result in the acquisition of new tumor cell properties. Therefore, therapeutic applications of MSC-derived secretome require much caution. 相似文献
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CARL RANDALL HARRELL ANA VOLAREVIC DRAGICA PAVLOVIC VALENTIN DJONOV VLADISLAV VOLAREVIC 《Biocell》2022,46(10):2195-2200
Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases. Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serious injury of corneal epithelial cells and retinal ganglion cell which may result in the vision loss. Mesenchymal stem cells (MSCs) are regulatory cells which produce various immunosuppressive factors that modulate phenotype and function of inflammatory immune cells. However, several safety issues, including undesired differentiation and emboli formation, limit clinical use of MSCs. MSC-derived exosomes (MSC-Exos) are nano-sized extracellular vesicles which contain all MSC-derived immunoregulatory factors. Intraocular administration of MSC-Exos efficiently attenuated eye inflammation and significantly improved visual acuity in experimental animals without causing any severe side effects. As cell-free product, MSC-Exos addressed all safety issues related to the transplantation of MSCs. Therefore, MSC-Exos could be considered as potentially new remedy for the treatment of inflammatory eye diseases which efficacy should be explored in up-coming clinical trials. 相似文献
3.
Mesenchymal stem cells (MSCs) have abilities to mediate tissue protection through mechanisms of anti-apoptosis, anti-oxidative stress and anti-fibrosis as well as tissue regeneration through mechanisms of cell proliferation, differentiation and angiogenesis. These effects by MSCs are mediated by a variety of factors, including growth factors, cytokines and extracellular vesicles (EVs). Among these factors, EVs, containing proteins, mRNA and microRNAs (miRNA), may carry their contents into distant tissues with high stability. Therefore, the treatment with MSC-derived EVs may be promising as ‘natural’ drug delivery systems (DDS). Especially, the treatment of MSC-derived EVs with the manipulation of specific miRNAs expression has been reported to be beneficial under a variety of diseases and tissue injuries. The overexpression of specific miRNAs in the EVs might be through pre-loading method using the gene editing system by plasmid vector or post-loading method to load miRNA mimics into EVs by electroporation or calcium chloride-mediated transfection. Despite current several challenges for clinical use, it should open the next era of regenerative medicine for a variety of diseases. In this article, we highlight the therapeutic potential of MSC-derived EVs as ‘natural’ DDS and current challenges. 相似文献
4.
Neurodegenerative disorders are a vicious woe to the public health and wellness. Uncertainty in their underlying causes, lack of effective biomarkers for their early detection, existence of only supportive therapy, and their ever rising incidence creates an unmatched need for targeted therapies. Mesenchymal Stem Cells (MSCs) have found to be promising candidates for regenerative and remedial therapy in neurodegenerative disorders, however several biological risks and practical issues impede in their translational utility. Deriving from MSCs are certain Extracellular Vesicles (EVs), which aid in the paracrine action of MSCs and have lately gained the scientific interest for their implacability in diverse set ups. Their cargo is of utmost importance and is being explored in various different diseases like heart diseases, neuronal diseases, respiratory diseases and hepatic diseases. They thereby hold the position of a likely prospective remedial candidate for therapy against neurodegenerative disorders. 相似文献
5.
The treatment of nonhealing and chronic cutaneous wounds still needs a clinical advancement to be effective.Both mesenchymal stem cells (MSCs), obtained from different sources, and their secretome derived thereof (especiallyexosomes) can activate signaling pathways related to promotion of cell migration, vascularization, collagen deposition,and inflammatory response demonstrating prohealing, angiogenetic and anti-scarring capacities. On the other hand,biodegradable biomimetic scaffolds can facilitate endogenous cell attachment and proliferation as well as extracellularmatrix production. In this Review, we revise the complex composites made by biomimetic scaffolds, mainly hydrogels,and MSC-derived exosomes constructed for cutaneous wound healing. Studies demonstrate that there exists asynergistic action of scaffolds with encapsulated exosomes, displaying a sustained release profiles to facilitate longlasting healing effects. It can be envisioned that dressings made by biomimetic hydrogels and MSC-derived exosomeswill be clinically applied in the near future for the effective treatment of nonhealing and chronic wounds. 相似文献
6.
SHADY G. EL-SAWAH FAYEZ ALTHOBAITI ADIL ALDHAHRANI EMAN FAYAD MARWA A. ABDEL-DAYEM REHAB M. AMEN EL SHAIMAA SHABANA EHAB I. EL-HALLOUS HANAN M. RASHWAN 《Biocell》2021,45(6):1561-1568
Diabetes mellitus (DM) could negatively affect patients’ health via inducing a lot of serious functional hazards in many tissues’ cells at molecular levels. Recently, many scientists had proposed stem cell therapy being an appropriate alternative treatment protocol for numerous health threatening issues including diabetes. Therefore, the current study was designed to investigate the antioxidant potentiality of two MSCs types in alleviating tissues’ oxidative stress dramatic elevation resulting as a consequence of Type 1 DM induction. In our 4 weeks study, animals were divided into four groups: control group, STZ-diabetic group (D), D+AD-MSCs group and D+BM-MSCs group. Data reported that diabetic rats treated with either AD-MSCs or BM-MSCs exhibited a marvelous body tissues (Pancreas, Liver and Kidney) enhancing capabilities in attenuating the oxidative stress status; as evidenced by XO, ROS, and MDA levels down-regulation; with a general concomitant elevation in the antioxidants’ content; evidenced by many enzymatic and non-enzymatic antioxidants up-regulation; relative to the diabetic untreated group. Interestingly, comparing both treatments with each other and to control group, most of the measured parameters were reverted back to near normal levels after AD-MSCs injection; which clearly point out their stunning health benefits and superiority as anti-diabetic agent in overcoming different tissues’ complications; owing to their marked cytoprotective and regenerative potentialities. 相似文献
7.
TRINIDAD MONTERO-VILCHEZ MANUEL SANCHEZ-DIAZ CAROLINA MONTERO-VILCHEZ ALVARO SIERRA-SANCHEZ SALVADOR ARIAS-SANTIAGO 《Biocell》2022,46(11):2363-2367
Atopic dermatitis (AD) is a chronic cutaneous inflammatory disease caused by an interaction between genetic, immune and epidermal barrier factors. Several treatments can be used to treat this disease but there are patients that do not respond to actual drugs. So, there is a need to develop effective therapies for AD. Mesenchymal stem cells (MSCs) are non-hematopoietic multipotent adult progenitor cells with immunomodulatory power and self-regenerating capacity to repair tissue damage, so they could be a potential effective treatment for AD. MSCs-Conditioned Medium (CM) and MSCs-exosomes are cell-free preparation with molecules secreted by stem cells that could be also beneficial for AD. This viewpoint reviews the actual development of MSCs, MSCs-CM and MSCs-exosomes for treating patients with AD. 相似文献
8.
DANILA BOBKOV ANASTASIA POLYANSKAYA ANASTASIA MUSORINA GALINA POLJANSKAYA 《Biocell》2022,46(9):2053-2058
All non-immortalized mesenchymal stem cells have a limited proliferative potential, that is, replicative senescence (RS) is an integral characteristic of the life of all mesenchymal stem cells (MSCs). It is known that one of the important signs of RS is a decrease of cell motility, and that violations of migration processes contribute to the deterioration of tissue regeneration. Therefore, the characterization of the properties of the cell line associated with RS is a prerequisite for the effective use of MSCs in restorative medicine. One of the key proteins regulating cell motility is the small GTPase RhoA. The main purpose of this work was to study the nuclear-cytoplasmic redistribution of the RhoA protein during RS in MSC lines recently obtained and characterized in our laboratory. The study found that a comparative analysis of the intracellular localization of RhoA in three cell lines (MSCWJ-1, FetMSC, DF2) showed a decrease in the nuclear localization of RhoA during RS. 相似文献
10.
Mesenchymal stem cells (MSCs) and their byproducts have been widely validated as potential therapeutic products for regenerative medicine. The therapeutic effects result mainly from the paracrine activity of MSCs, which consists of the secretion of bioactive molecules, whether dispersed in medium conditioned by cell culture or encapsulated in extracellular vesicles. The composition of the MSC secretome, which represents the set of these secreted cellular products, is crucial for the performance of the desired therapeutic functions. Different cell culture strategies have been employed to adjust the secretome composition of MSCs to obtain the best therapeutic responses for different clinical contexts. However, the manipulation of culture conditions has focused mainly on the use of different biochemical elements for the preconditioning of MSCs and less on the physical conditions of the cell culture environment. Herein, we offer our point of view regarding the importance of the physical properties of cell culture substrates and their mechanotransduction responses in preconditioning the MSCs secretome. We highlight the relevance of studying mechanotransduction events associating cell morphology and the modulation of gene expression to customize and expand the use of MSCs secretomes. 相似文献
11.
XIAOXU ZHANG LIN ZHANG LIN DU HUIYAN SUN XIA ZHAO YANG SUN WEI WANG LISHENG WANG 《Biocell》2023,47(2):385-392
Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and clinical therapy due to their capabilities of proliferation, differentiation, and immune regulation. However, during in vitro expansion, MSCs are prone to aging, which largely limits their application. Prostaglandin E-2 (PGE-2) is a key effector secreted by MSCs to exert immunomodulatory effects. By screening the compound library for PGE-2 secretion, the antioxidant trolox was verified as a stimulator of MSCs to secrete PGE-2. The effect of antioxidant trolox on biological characteristics of MSCS, including aging, proliferation, and gene expression, was examined. The results demonstrated that trolox can resist aging, promote proliferation, and enhance PGE-2 secretion of MSCs without affecting their surface marker expression. Furthermore, trolox treatment up-regulates miR-17-92 clusters in MSCs and may contribute to its anti-aging effects. Thus, trolox addition might be beneficial for MSCs expansion and their application. 相似文献
12.
Mesenchymal stem cells (MSCs) play key roles in regenerative medicine by promoting tissue healing. MSCs can be isolated from different adult tissues and they are able to differentiate into several lineages. Due to their anti-inflammatory, angiogenic and immune-modulatory properties, MSCs are suitable for tissue engineering applications and, when associated with biomaterials, their benefits can be improved. Moreover, recently, MSCs have been studied for new clinical applications, such as in the treatment of patients with COVID-19. MSCs regenerative potential has been attributed to their secretome, which comprises extracellular matrix, soluble proteins and several elements, including the release of extracellular vesicles. Even though, in order to explore all their therapeutic potential, it is still necessary to advance in the investigation of their basic cell biology characteristics. 相似文献
13.
ADRIANA L. FERREIRA GUSTAVO C. PARIS ALINE DE A. AZEVEDO ERIKA A. C. CORTEZ SIMONE N. CARVALHO LAIS DE CARVALHO ALESSANDRA A. THOLE 《Biocell》2022,46(8):1807-1813
Mesenchymal stem cells (MSC) have pushed the field of stem cell-based therapies by inducing tissueregeneration, immunosuppression, and angiogenesis mainly through vesicles and soluble factors release (paracrinesignaling). MSC-extracellular vesicles (MSC-EV) adaptable secretome and homing to injured sites allowed researchersto unlock a new era of cell-free based therapy. In parallel, nanoparticles (NP) have been explored in contributing totransport and drug delivery systems, giving drugs desired physical-chemical properties to exploit cell behavior.However, NPs can be quickly recognized by immune cells and cleared from circulation. In this viewpoint, we explorehow combining both therapeutic strategies can improve efficacy and circumvent limitations of both therapies. MSCEV benefit from the potent MSC membrane composition, guiding chemotaxis to tumor sites, a very restrictedmicroenvironment. MSC-EV has low immunogenicity, high stability, long half-life and can explore tissue targetingligands as a precise drug carry, even across biological barriers. Those properties promote enhanced targeted drugdelivery that can be combined with NP, exploring biological membrane production through: 1. direct cell therapywith NP-infused MSC; 2. NP-containing MSC-EV generated by NP-infused MSC; 3. by coating NP in MSCmembrane (“MSC NanoGhosts”), allowing precise cargo definition without losing targeting. Therefore,nanotechnology combined with cell-based therapeutic resources can greatly improve targeted drug delivery, improvingefficacy and opening a new venue of therapeutic possibilities. 相似文献
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This work aimed to investigate the effects of calcitonin gene-related peptide (CGRP)-modified mesenchymal stem cells (MSCs) on vascular stenosis in carotid balloon-injured rats. The CGRP gene labeled with EGFP was transfected into bone marrow MSCs, and CGRP protein expression in MSCs was confirmed by immunofluorescence assays. A rat carotid balloon injury model was established using a surgical method. CGRP-modified MSCs were orthotopically transplanted into the injured area of the rats. At 28 days after cell transplantation, EGFP and CD31 expression was detected by immunofluorescence staining. Hematoxylin-eosin (H&E) staining was used to detect the intima/media area of the injured carotid artery stenosis site, and the expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. MSCs from rat bone marrow positively expressed CD29 and negatively expressed CD45. In vivo immunofluorescence staining showed that EGFP expression was significantly increased at the vascular injury site of rats transplanted with MSC_CGRP compared with the control group on the 28th day after cell transplantation and that the damaged vessels exhibited continuous CD31 expression. H&E staining showed that the vascular intimal proliferation area of rats transplanted with MSC_CGRP was significantly reduced compared with that of other groups. Furthermore, the immunohistochemistry results showed that PCNA expression in the endothelium of the MSC_CGRP group was lower than that of the other groups. Therefore, MSCs transfected with the CGRP gene can express the CGRP protein, and the implantation of CGRP-modified MSCs at the damaged site after carotid balloon-induced injury can reduce the neointimal area. 相似文献
16.
IGOR A. KHLUSOV LARISA S. LITVINOVA KRISTINA A. YUROVA MARINA Y. KHLUSOVA 《Biocell》2022,46(6):1365-1373
Stem cell microterritories (niches), as a specialized part of the extracellular matrix (ECM), are considered an important target and tool for the development of new materials, medical implants, and devices. However, tissue bioengineering products that have stem cell niches of known size on the surface or in the bulk structure of artificial materials are practically unknown. This brief review attempts to draw attention to the problematic aspects of niches as specific parts of the ECM, such as their hierarchy and size for mesenchymal stromal/stem cells (MSCs). These parameters arise directly from numerous definitions of stem cell niches as specialized morphological microterritories found in various tissues. The authors of this review analyze the known information on the hierarchy of MSC microterritories by analogy with that of hematopoietic stem cells. Occasional reports on the size of artificial MSC niches compared to natural niche candidates are summarized. A consensus on a hierarchy and optimal range of niche sizes for MSCs and other stem cells is needed to accelerate the development of prototyping technologies and additive manufacturing in applications to precise tissue bioengineering and regenerative medicine. 相似文献
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Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cell-based product, there appears to be evidence of superior effect and heightened potential success in its expressed vesicles, exosomes, as cell-free products. In addition to their highly desirable intrinsic biologically unique structural, compositional, and morphological characteristics, as well as predominant physiochemical stability and biocompatibility properties, exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. More importantly, the powerful therapeutic potential and superior biological functions of exosomes, particularly, regarding engineered exosomes as cell-free products, and their utilization in a new generation of nanomedicine treatment, vaccination, and diagnosis platforms, brings hope of a change in the near future. This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer. 相似文献
19.
Human-induced neural stem cells (iNSCs) transplantation is a potential treatment of neurodegenerationdiseases. However, whether the reprogrammed cells have the same characterizations as human fetal neural stem cellsneeds further exploration. Here we isolated human fetal neural stem cells from aborted 12-week fetal brains andcompared with iNSCs reprogrammed from human peripheral blood mononuclear cells in gene expression, proliferationability, differentiation capacity, and the responses to tumor necrosis factor-α. We found that iNSCs and NSCs bothexpressed neural stem cell markers Nestin, SOX1, and SOX2. However, only iNSCs can be patterned into dopaminergicneurons and motor neurons. Furthermore, both iNSCs and NSCs can differentiate into oligodendrocyte progenitorcells. In addition, a low dose of tumor necrosis factor-α did not inhibit the proliferation and differentiation of iNSCsand NSCs. In conclusion, iNSCs have properties similar to, and even better than, fetal neural stem cells and may besuitable for disease modeling and transplantation. 相似文献
20.
Macrophages play an essential role in the myocardial ischemia-reperfusion injury (MIRI), and the macrophageshifting from M1 to M2 phenotypes might be a potential strategy for the treatment of MIRI. It has been reported thatmiR-182 plays an important role in MSC-Exo-associated macrophage polarization. As circBCRC-3 is a newlydiscovered circle RNA that worked as a sponge of miR-182, this research aimed to find if circBCRC-3 plays a role inMSC-Exo-associated macrophage polarization. Firstly, circBCRC-3 was identified by divergent primers inmesenchymal stem cells (MSCs). Secondly, the exosome of MSCs was isolated and identified by transmission electronmicroscopy (TEM), nanoparticle-tracking analysis, and western blotting analysis. The expression level of circBCRC-3in MSCexos was detected by RT-PCR. Finally, the polarization of the RAW264.7 cell phenotype was analyzed by flowcytometry. Moreover, we first identified circBCRC-3 in MSCs. The results further confirmed that MSCexo couldeffectively shift the macrophage polarization state from M1 towards the M2 phenotype, which indicated its rolein MIRI cure. 相似文献