Diagnostic and Therapeutic Role of Extracellular Vesicles in Articular Cartilage Lesions and Degenerative Joint Diseases

Two leading contributors to the global disability are cartilage lesions and degenerative joint diseases, which are characterized by the progressive cartilage destruction. Current clinical treatments often fail due to variable outcomes and an unsatisfactory long-term repair. Cell-based therapies were once considered as an effective solution because of their anti-inflammatory and immunosuppression characteristics as well as their differentiation capacity to regenerate the damaged tissue. However, stem cell-based therapies have inherent limitations, such as a high tumorigenicity risk, a low retention, and an engraftment rate, as well as strict regulatory requirements, which result in an underwhelming therapeutic effect. Therefore, the non-stem cell-based therapy has gained its popularity in recent years. Extracellular vesicles (EVs), in particular, like the paracrine factors secreted by stem cells, have been proven to play a role in mediating the biological functions of target cells, and can achieve the therapeutic effect similar to stem cells in cartilage tissue engineering. Therefore, a comprehensive review of the therapeutic role of EVs in cartilage lesions and degenerative joint diseases can be discussed both in terms of time and favorability. In this review, we summarized the physiological environment of a joint and its pathological alteration after trauma and consequent changes in EVs, which are lacking in the current literature studies. In addition, we covered the potential working mechanism of EVs in the repair of the cartilage and the joint and also discussed the potential therapeutic applications of EVs in future clinical use.

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Embryonic stem cell-derived extracellular vesicles enhance the therapeutic effect of mesenchymal stem cells

Theranostics ◽

10.7150/thno.35305 ◽

2019 ◽

Vol 9 (23) ◽

pp. 6976-6990 ◽

Cited By ~ 6

Author(s):

Yan Zhang ◽

Jia Xu ◽

Siying Liu ◽

Meikuang Lim ◽

Shuang Zhao ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Therapeutic Effect ◽

Extracellular Vesicles ◽

Embryonic Stem

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Extracellular Vesicles: Evolving Factors in Stem Cell Biology

Stem Cells International ◽

10.1155/2016/1073140 ◽

2016 ◽

Vol 2016 ◽

pp. 1-17 ◽

Cited By ~ 88

Author(s):

Muhammad Nawaz ◽

Farah Fatima ◽

Krishna C. Vallabhaneni ◽

Patrice Penfornis ◽

Hadi Valadi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Tumor Microenvironment ◽

Extracellular Vesicles ◽

Cell Biology ◽

Trophic Factors ◽

Stem Cell Biology ◽

Cell Fates ◽

Bidirectional Communication

Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

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Therapeutic role of extracellular vesicles derived from stem cells in cutaneous wound models: A systematic review

Life Sciences ◽

10.1016/j.lfs.2021.119271 ◽

2021 ◽

pp. 119271

Author(s):

Razieh Dalirfardouei ◽

Aida Gholoobi ◽

Mehrangiz Vahabian ◽

Elahe Mahdipour ◽

Fahimeh Afzaljavan

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Extracellular Vesicles ◽

Therapeutic Role ◽

Cutaneous Wound

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Therapeutic Role of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells

10.21236/ada598365 ◽

2013 ◽

Author(s):

Isaac Y. Kim ◽

Joseph Bertino ◽

Hatem E. Sabaawy

Keyword(s):

Stem Cells ◽

Prostate Tumor ◽

Tumor Stem Cells ◽

Therapeutic Role

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Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

International Journal of Molecular Sciences ◽

10.3390/ijms22031375 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1375

Author(s):

María Carmen Carceller ◽

María Isabel Guillén ◽

María Luisa Gil ◽

María José Alcaraz

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Extracellular Vesicles ◽

Nuclear Factor Κb ◽

Peritoneal Macrophages ◽

Toll Like Receptor 4 ◽

Anti Inflammatory ◽

Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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Cell Source-Dependent In Vitro Chondrogenic Differentiation Potential of Mesenchymal Stem Cell Established from Bone Marrow and Synovial Fluid of Camelus dromedarius

Animals ◽

10.3390/ani11071918 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1918

Author(s):

Young-Bum Son ◽

Yeon Ik Jeong ◽

Yeon Woo Jeong ◽

Mohammad Shamim Hossein ◽

Per Olof Olsson ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Synovial Fluid ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Chondrocyte Differentiation ◽

Differentiation Potential ◽

Proliferation Capacity

Mesenchymal stem cells (MSCs) are promising multipotent cells with applications for cartilage tissue regeneration in stem cell-based therapies. In cartilage regeneration, both bone marrow (BM-MSCs) and synovial fluid (SF-MSCs) are valuable sources. However, the cellular characteristics and chondrocyte differentiation potential were not reported in either of the camel stem cells. The in vitro chondrocyte differentiation competence of MSCs, from (BM and SF) sources of the same Camelus dromedaries (camel) donor, was determined. Both MSCs were evaluated on pluripotent markers and proliferation capacity. After passage three, both MSCs showed fibroblast-like morphology. The proliferation capacity was significantly increased in SF-MSCs compared to BM-MSCs. Furthermore, SF-MSCs showed an enhanced expression of transcription factors than BM-MSCs. SF-MSCs exhibited lower differentiation potential toward adipocytes than BM-MSCs. However, the osteoblast differentiation potential was similar in MSCs from both sources. Chondrogenic pellets obtained from SF-MSCs revealed higher levels of chondrocyte-specific markers than those from BM-MSCs. Additionally, glycosaminoglycan (GAG) content was elevated in SF-MSCs related to BM-MSCs. This is, to our knowledge, the first study to establish BM-MSCs and SF-MSCs from the same donor and to demonstrate in vitro differentiation potential into chondrocytes in camels.

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Mesenchymal Stem Cells Do Not Lose Direct Labels Including Iron Oxide Nanoparticles and DFO-89Zr Chelates through Secretion of Extracellular Vesicles

Membranes ◽

10.3390/membranes11070484 ◽

2021 ◽

Vol 11 (7) ◽

pp. 484

Author(s):

Yue Gao ◽

Anna Jablonska ◽

Chengyan Chu ◽

Piotr Walczak ◽

Miroslaw Janowski

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Oxide ◽

Iron Oxide Nanoparticles ◽

Extracellular Vesicles ◽

Superparamagnetic Iron Oxide ◽

Cell Labeling ◽

Oxide Nanoparticles ◽

Stem Cell Delivery ◽

Cellular Labeling

Rapidly ageing populations are beset by tissue wear and damage. Stem cell-based regenerative medicine is considered a solution. Years of research point to two important aspects: (1) the use of cellular imaging to achieve sufficient precision of therapeutic intervention, and the fact that (2) many therapeutic actions are executed through extracellular vesicles (EV), released by stem cells. Therefore, there is an urgent need to interrogate cellular labels in the context of EV release. We studied clinically applicable cellular labels: superparamagnetic iron oxide nanoparticles (SPION), and radionuclide detectable by two main imaging modalities: MRI and PET. We have demonstrated effective stem cell labeling using both labels. Then, we obtained EVs from cell cultures and tested for the presence of cellular labels. We did not find either magnetic or radioactive labels in EVs. Therefore, we report that stem cells do not lose labels in released EVs, which indicates the reliability of stem cell magnetic and radioactive labeling, and that there is no interference of labels with EV content. In conclusion, we observed that direct cellular labeling seems to be an attractive approach to monitoring stem cell delivery, and that, importantly, labels neither locate in EVs nor affect their basic properties.

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