scholarly journals Concise review: Extracellular vesicles from mesenchymal stem cells as cellular therapy

2017 ◽  
Vol 4 (08) ◽  
Author(s):  
Phuc Van Pham
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
High Performance ◽  
Cellular Therapy ◽  
Biological Properties ◽  
Concise Review ◽  
Cord Injury ◽  
New Generation

Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are microvesicles produced from cells throughout their life. From research over recent years, there has been greater understanding about EVs, including their physiological characteristics and the role they play in cell targets. Indeed, EVs carry information (in the form of RNA, DNA and protein) to cell targets. Some of their main biological properties include angiogenesis and immune-modulation. Therefore, these properties can be exploited to treat various diseases, including bone disorders, spinal cord injury and diabetes mellitus. Recently, new methods have been developed to isolate and enrich EVs with high performance and low-toxicity. Thus, EVs have emerged as the new generation of stem cell therapy. This concise review aims to highlight some recent achievements of EVs in preclinical and clinical applications.

scholarly journals Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis

2021 ◽  
Vol 10 (5) ◽  
pp. 328-339
Author(s):  
Xufeng Jia ◽  
Guangping Huang ◽  
Shaohua Wang ◽  
Miao Long ◽  
Xiaojun Tang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Cord Injury ◽  
Neuron Apoptosis

Aims Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. Methods In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. Results We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. Conclusion Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339.

Isolation and Characterization of Rat Mesenchymal Stem Cells Derived from Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood

2016 ◽  
Vol 201 (6) ◽  
pp. 412-422 ◽  
Author(s):  
Qiang Fu ◽  
Qian Zhang ◽  
Lin Ying Jia ◽  
Ning Fang ◽  
Long Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Blood ◽  
Cellular Therapy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cell Based Therapy ◽  
Isolation And Characterization ◽  
Cord Injury ◽  
Stimulating Factor

Mesenchymal stem cells (MSCs) have been isolated from many tissues and organs. However, there is much dispute as to whether MSCs exist in peripheral blood. This may be due to the limited identification methods of MSCs, especially the lack of detection markers for phenotypic characteristics. In this study, as many as 10 surface markers of MSCs derived from rat peripheral blood (rPBMSCs) were analyzed after granulocyte colony-stimulating factor mobilization. Our results suggest that mobilized rPBMSCs overexpress mesenchymal markers, including CD90, CD44, CD29, CD73 and CD105, but do not express CD45, CD11b, CD79a, CD34 or HLA-DR. This is in conformity with the standard definition of MSCs by the International Society for Cellular Therapy. In addition, the colony-forming efficiency of the mobilized rat peripheral blood was 15.83 ± 1.61/106, significantly outnumbering that of the nonmobilized group, which was 0.28 ± 0.1/106 (p < 0.01). Combining the growth characteristics with the differential capacities of mobilized rPBMSCs towards forming osteocytes, chondrocytes and adipocytes, we further confirmed the existence of rPBMSCs. Additionally, this treatment could improve locomotive function after spinal cord injury (SCI) in rats. Due to their convenient collection, fewer complications, cost effectiveness and suitability for autograft, PBMSCs might be a substitute for MSCs derived from bone marrow and provide promising prospects for the cell-based therapy of SCI.

scholarly journals Extracellular vesicles derived from CD73 modified human umbilical cord mesenchymal stem cells ameliorate inflammation after spinal cord injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiao Zhai ◽  
Kai Chen ◽  
Huan Yang ◽  
Bo Li ◽  
Tianjunke Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Human Umbilical Cord ◽  
M1 Polarization ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI. Methods CD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications. Results CD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4. Conclusions CD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy. Graphical Abstract

scholarly journals Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao Xiao ◽  
Weiwei Li ◽  
Dingchao Rong ◽  
Zhenchao Xu ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Motor Function ◽  
Extracellular Vesicles ◽  
Human Umbilical Cord ◽  
Permanent Disability ◽  
Cord Injury

AbstractSpinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

scholarly journals Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 22 ◽  
Author(s):  
Teresa Raquel Tavares Serejo ◽  
Amandda Évelin Silva-Carvalho ◽  
Luma Dayane de Carvalho Filiú Braga ◽  
Francisco de Assis Rocha Neves ◽  
Rinaldo Wellerson Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Extracellular Vesicles ◽  
Cellular Therapy ◽  
T Cell Proliferation ◽  
Cell Contact ◽  
A Cell ◽  
Immunomodulatory Function

There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in order to avoid the complexity of a cellular therapy. Here, we investigate the effects of human adipose MSCs (AMSCs) licensing with INF-γ and TLR3 agonist over AMSCs proliferation, migration, as well as the immunomodulatory function. Furthermore, we evaluated how the licensing of AMSCs affected the immunomodulatory function of AMSC derived-secretome, including their EVs. INF-γ licensed-AMSCs presented an elevated expression of indoleamine 2,3-dioxygenase (IDO), accompanied by increased ICAM-1, as well as a higher immunosuppressive potential, compared to unlicensed AMSCs. Interestingly, the conditioned medium obtained from INF-γ licensed-AMSCs also revealed a slightly superior immunosuppressive potential, compared to other licensing strategies. Therefore, unlicensed and INF-γ licensed-AMSCs groups were used to isolate EVs. Interestingly, EVs isolated from both groups displayed similar capacity to inhibit T-cell proliferation. EVs isolated from both groups shared similar TGF-β and Galectin-1 mRNA content but only EVs derived from INF-γ licensed-AMSCs expressed IDO mRNA. In summary, we demonstrated that INF-γ licensing of AMSCs provides an immunosuppressive advantage both from a cell-cell contact-dependent perspective, as well as in a cell-free context. Interestingly, EVs derived from unlicensed and INF-γ licensed-AMSCs have similar ability to control activated T-cell proliferation. These results contribute towards the development of new strategies to control the immune response based on AMSCs or their derived products.

Regenerative potential of Stem cell-derived extracellular vesicles in spinal cord injury (SCI)

2021 ◽  
Vol 16 ◽  
Author(s):  
Franklin J Herbert ◽  
Dhivya Bharathi ◽  
Sevanthy Suresh ◽  
Ernest David ◽  
Sanjay Kumar
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Cell Therapy ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
Cell Types ◽  
Medical Attention ◽  
Cord Injury

: Spinal cord injury is a devastating condition that is critically challenging and progressive, needing immediate medical attention due to its complex pathophysiology and affecting the social status and economic burden. Stem cell therapy has been the emerging therapeutic trend to treat various diseases for decades. Mesenchymal stem cells pose more advantages over other stem cells in immune-modulation, immune evasiveness, self-renewal, multipotency, etc. Due to various issues in the recent past related to allogenic transplants, ethical concerns in obtaining tissues and adult cells, host immune response, GMP grade production and certification, cell-derived products or cell secretome have proven to be a promising approach and have been implicated in many studies and also in many clinical trials. Utilization of these human MSC-derived exosomes/extracellular vesicles in spinal cord injury has also been demonstrated in many pre-clinical animal models. It is now proven to be therapeutically more efficient and safer than cell therapy. This review focuses on employing human MSC derived EVs for SCI and continues to elucidate the recent advances and emerging EVs trends from other cell types. We discuss biomaterial-based synergistic intervention, mention mimetics and nanovesicles and finally touch upon safety concerns in EV therapy.

Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

2020 ◽  
Vol 21 ◽  
Author(s):  
Mohammad Saeedi ◽  
Muhammad Sadeqi Nezhad ◽  
Fatemeh Mehranfar ◽  
Mahdieh Golpour ◽  
Mohammad Ali Esakandari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Immune Modulation ◽  
Adult Stem Cells ◽  
Inflammatory Diseases ◽  
High Capacity ◽  
Genetically Engineered ◽  
Cartilage Cells ◽  
Biological Aspects

: Mesenchymal stem cells (MSCs), a form of adult stem cells, are known to have a self-renewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and its high capacity of immune modulation has attracted tremendous attention for exerting them in clinical purposes, as they contribute to tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a state-of-the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs physiological interaction, such as migration, homing, and tissue repairing mechanisms with different healthy and inflamed tissues.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

2020 ◽  
Vol 15 (7) ◽  
pp. 623-638
Author(s):  
Saeideh Gholamzadeh Khoei ◽  
Fateme Karimi Dermani ◽  
Sara Malih ◽  
Nashmin Fayazi ◽  
Mohsen Sheykhhasan
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Adult Stem Cells ◽  
Heart Diseases ◽  
Therapeutic Option ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

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