scholarly journals Cell Interplay in Osteoarthritis

Author(s):  
Zihao Li ◽  
Ziyu Huang ◽  
Lunhao Bai

Osteoarthritis (OA) is a common chronic disease and a significant health concern that needs to be urgently solved. OA affects the cartilage and entire joint tissues, including the subchondral bone, synovium, and infrapatellar fat pads. The physiological and pathological changes in these tissues affect the occurrence and development of OA. Understanding complex crosstalk among different joint tissues and their roles in OA initiation and progression is critical in elucidating the pathogenic mechanism of OA. In this review, we begin with an overview of the role of chondrocytes, synovial cells (synovial fibroblasts and macrophages), mast cells, osteoblasts, osteoclasts, various stem cells, and engineered cells (induced pluripotent stem cells) in OA pathogenesis. Then, we discuss the various mechanisms by which these cells communicate, including paracrine signaling, local microenvironment, co-culture, extracellular vesicles (exosomes), and cell tissue engineering. We particularly focus on the therapeutic potential and clinical applications of stem cell-derived extracellular vesicles, which serve as modulators of cell-to-cell communication, in the field of regenerative medicine, such as cartilage repair. Finally, the challenges and limitations related to exosome-based treatment for OA are discussed. This article provides a comprehensive summary of key cells that might be targets of future therapies for OA.

2016 ◽  
Vol 311 (5) ◽  
pp. F844-F851 ◽  
Author(s):  
Wei Zhang ◽  
Xiangjun Zhou ◽  
Hao Zhang ◽  
Qisheng Yao ◽  
Yutao Liu ◽  
...  

Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoyan Zhang ◽  
Huaijun Tu ◽  
Yazhi Yang ◽  
Lijun Fang ◽  
Qiong Wu ◽  
...  

Mesenchymal stem cells (MSCs) are ubiquitously present in many tissues. Due to their unique advantages, MSCs have been widely employed in clinical studies. Emerging evidences indicate that MSCs can also migrate to the tumor surrounding stroma and exert complex effects on tumor growth and progression. However, the effect of MSCs on tumor growth is still a matter of debate. Several studies have shown that MSCs could favor tumor growth. On the contrary, other groups have demonstrated that MSCs suppressed tumor progression. Extracellular vesicles have emerged as a new mechanism of cell-to-cell communication in the development of tumor diseases. MSCs-derived extracellular vesicles (MSC-EVs) could mimic the effects of the mesenchymal stem cells from which they originate. Different studies have reported that MSC-EVs may exert various effects on the growth, metastasis, and drug response of different tumor cells by transferring proteins, messenger RNA, and microRNA to recipient cells. In the present review, we summarize the components of MSC-EVs and discuss the roles of MSC-EVs in different malignant diseases, including the related mechanisms that may account for their therapeutic potential. MSC-EVs open up a promising opportunity in the treatment of cancer with increased efficacy.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ilaria Laurenzana ◽  
Daniela Lamorte ◽  
Stefania Trino ◽  
Luciana De Luca ◽  
Concetta Ambrosino ◽  
...  

The bone marrow (BM) microenvironment in hematological malignancies (HMs) comprises heterogeneous populations of neoplastic and nonneoplastic cells. Cancer stem cells (CSCs), neoplastic cells, hematopoietic stem cells (HSCs), and mesenchymal stromal/stem cells (MSCs) are all components of this microenvironment. CSCs are the HM initiators and are associated with neoplastic growth and drug resistance, while HSCs are able to reconstitute the entire hematopoietic system; finally, MSCs actively support hematopoiesis. In some HMs, CSCs and neoplastic cells compromise the normal development of HSCs and perturb BM-MSCs. In response, “reprogrammed” MSCs generate a favorable environment to support neoplastic cells. Extracellular vesicles (EVs) are an important cell-to-cell communication type in physiological and pathological conditions. In particular, in HMs, EV secretion participates to unidirectional and bidirectional interactions between neoplastic cells and BM cells. The transfer of EV molecular cargo triggers different responses in target cells; in particular, malignant EVs modify the BM environment in favor of neoplastic cells at the expense of normal HSCs, by interfering with antineoplastic immunity and participating in resistance to treatment. Here, we review the role of EVs in BM cell communication in physiological conditions and in HMs, focusing on the effects of BM niche EVs on HSCs and MSCs.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1287
Author(s):  
Nur Azira Mohd Noor ◽  
Asma Abdullah Nurul ◽  
Muhammad Rajaei Ahmad Mohd Zain ◽  
Wan Khairunnisaa Wan Nor Aduni ◽  
Maryam Azlan

Osteoarthritis (OA) is a chronic degenerative disorder of the joint and its prevalence and severity is increasing owing to ageing of the population. Osteoarthritis is characterized by the degradation of articular cartilage and remodeling of the underlying bone. There is little understanding of the cellular and molecular processes involved in pathophysiology of OA. Currently the treatment for OA is limited to painkillers and anti-inflammatory drugs, which only treat the symptoms. Some patients may also undergo surgical procedures to replace the damaged joints. Extracellular vesicles (EV) play an important role in intercellular communications and their concentration is elevated in the joints of OA patients, although their mechanism is unclear. Extracellular vesicles are naturally released by cells and they carry their origin cell information to be delivered to target cells. On the other hand, mesenchymal stem cells (MSCs) are highly proliferative and have a great potential in cartilage regeneration. In this review, we provide an overview of the current OA treatments and their limitations. We also discuss the role of EV in OA pathophysiology. Finally, we highlight the therapeutic potential of MSC-derived EV in OA and their challenges.


2020 ◽  
Vol 9 (3) ◽  
pp. 856 ◽  
Author(s):  
Aristea K. Batsali ◽  
Anthie Georgopoulou ◽  
Irene Mavroudi ◽  
Angelos Matheakakis ◽  
Charalampos G. Pontikoglou ◽  
...  

Mesenchymal stem cells (MSCs) represent a heterogeneous cellular population responsible for the support, maintenance, and regulation of normal hematopoietic stem cells (HSCs). In many hematological malignancies, however, MSCs are deregulated and may create an inhibitory microenvironment able to induce the disease initiation and/or progression. MSCs secrete soluble factors including extracellular vesicles (EVs), which may influence the bone marrow (BM) microenvironment via paracrine mechanisms. MSC-derived EVs (MSC-EVs) may even mimic the effects of MSCs from which they originate. Therefore, MSC-EVs contribute to the BM homeostasis but may also display multiple roles in the induction and maintenance of abnormal hematopoiesis. Compared to MSCs, MSC-EVs have been considered a more promising tool for therapeutic purposes including the prevention and treatment of Graft Versus Host Disease (GVHD) following allogenic HSC transplantation (HSCT). There are, however, still unanswered questions such as the molecular and cellular mechanisms associated with the supportive effect of MSC-EVs, the impact of the isolation, purification, large-scale production, storage conditions, MSC source, and donor characteristics on MSC-EV biological effects as well as the optimal dose and safety for clinical usage. This review summarizes the role of MSC-EVs in normal and malignant hematopoiesis and their potential contribution in treating GVHD.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jie Chen ◽  
Chonghui Li ◽  
Liangan Chen

Microvesicles (MVs) are membrane vesicles that are released by many types of cells and have recently been considered important mediators of cell-to-cell communication. MVs serve as a vehicle to transfer proteins and messenger RNA and microRNA (miRNA) to distant cells, which alters the gene expression, proliferation, and differentiation of the recipient cells. Several studies have demonstrated that mesenchymal stem cells (MSCs) have the capacity to reverse acute and chronic lung injury in different experimental models through paracrine mechanisms. This paracrine action may be partially accounted for by MVs that are derived from MSCs. MSC-derived MVs may confer a stem cell-like phenotype to injured cells with the consequent activation of self-regenerative programmers. In this review, we summarize the characteristics and biological activities of MSC-derived MVs, and we describe their potential in novel therapeutic approaches in regenerative medicine to repair damaged tissues. Additionally, we provide an overview of studies that have assessed the role of MSC-derived MVs in lung diseases, including the mechanisms that may account for their therapeutic potential. Finally, we discuss the clinical use of MSC-derived MVs with several suggestions for enhancing their therapeutic efficiency.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Marta Garcia-Contreras ◽  
Avnesh S. Thakor

AbstractNeurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), are driven by neuroinflammation triggered by activated microglial cells; hence, the phenotypic regulation of these cells is an appealing target for intervention. Human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) may be a potential therapeutic candidate to treat NDs given their immunomodulatory properties. Evidence suggests that the mechanism of action of hAD-MSCs is through their secretome, which includes secreted factors such as cytokines, chemokines, or growth factors as well as extracellular vesicles (EVs). Recently, EVs have emerged as important mediators in cell communication given, they can transfer proteins, lipids, and RNA species (i.e., miRNA, mRNA, and tRNAs) to modulate recipient cells. However, the therapeutic potential of hAD-MSCs and their secreted EVs has not been fully elucidated with respect to human microglia. In this study, we determined the therapeutic potential of different hAD-MSCs doses (200,000, 100,000, and 50,000 cells) or their secreted EVs (50, 20, or 10 µg/ml), on human microglial cells (HMC3) that were activated by lipopolysaccharides (LPS). Upregulation of inducible nitric oxide synthase (iNOS), an activation marker of HMC3 cells, was prevented when they were cocultured with hAD-MSCs and EVs. Moreover, hAD-MSCs inhibited the secretion of proinflammatory factors, such as IL-6, IL-8, and MCP-1, while their secreted EVs promoted the expression of anti-inflammatory mediators such as IL-10 or TIMP-1 in activated microglia. The present data therefore support a role for hAD-MSCs and their secreted EVs, as potential therapeutic candidates for the treatment of NDs.


Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1858
Author(s):  
Shu Hua ◽  
Peter Mark Bartold ◽  
Karan Gulati ◽  
Corey Stephen Moran ◽  
Sašo Ivanovski ◽  
...  

Extracellular vesicles (EVs) are membrane-bound lipid particles that are secreted by all cell types and function as cell-to-cell communicators through their cargos of protein, nucleic acid, lipids, and metabolites, which are derived from their parent cells. There is limited information on the isolation and the emerging therapeutic role of periodontal and dental pulp cell-derived small EVs (sEVs, <200 nm, or exosome). In this review, we discuss the biogenesis of three EV subtypes (sEVs, microvesicles and apoptotic bodies) and the emerging role of sEVs from periodontal ligament (stem) cells, gingival fibroblasts (or gingival mesenchymal stem cells) and dental pulp cells, and their therapeutic potential in vitro and in vivo. A review of the relevant methodology found that precipitation-based kits and ultracentrifugation are the two most common methods to isolate periodontal (dental pulp) cell sEVs. Periodontal (and pulp) cell sEVs range in size, from 40 nm to 2 μm, due to a lack of standardized isolation protocols. Nevertheless, our review found that these EVs possess anti-inflammatory, osteo/odontogenic, angiogenic and immunomodulatory functions in vitro and in vivo, via reported EV cargos of EV–miRNAs, EV–circRNAs, EV–mRNAs and EV–lncRNAs. This review highlights the considerable therapeutic potential of periodontal and dental pulp cell-derived sEVs in various regenerative applications.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fereshteh Bayat ◽  
Alireza Afshar ◽  
Neda Baghban

Extracellular vesicles (EVs) originated from different cells of approximately all kinds of organisms, recently got more attention because of their potential in the treatment of diseases and reconstructive medicine. To date, lots of studies have been performed on mammalian-derived vesicles, but little attention has been paid to algae and marine cells as valuable sources of EVs. Proving the promising role of EVs in medicine requires sufficient resources to produce qualified microvesicles. Algae, same as its other sister groups, such as plants, have stem cells and stem cell niches. Previous studies showed the EVs in plants and marine cells. So, this study was set out to talk about algal extracellular vesicles. EVs play a major role in cell-to-cell communication to convey molecules, such as RNA/DNA, metabolites, proteins, and lipids within. The components of EVs depends on the origin of the primitive cells or tissues and the isolation method. Sufficient resources are needed to produce high-quality, stable, and compatible EVs as a drug or drug delivery system. Plant stem cells have great potential as a new controllable resource for the production of EVs. The EVs secreted from stem cells can easily be extracted from the cell culture medium and evaluated for medicinal uses. In this review, the aim is to introduce algae stem cells as well as EVs derived from algal cells. In the following, the production of the EVs¸ the properties of EVs extracted from these sources and their antimicrobial effects will be discussed.


2021 ◽  
Vol 22 (7) ◽  
pp. 3367
Author(s):  
Rocío Mato-Basalo ◽  
Miriam Morente-López ◽  
Onno J Arntz ◽  
Fons A. J. van de Loo ◽  
Juan Fafián-Labora ◽  
...  

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.


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