scholarly journals Exosomes From Human Umbilical Cord-derived Mesenchymal Stem Cells Alleviate Osteoarthritis by Balancing the Synthesis and Degradation of Cartilage Extracellular Matrix and Regulating Macrophage Polarization

Author(s):  
Pengdong Li ◽  
Shuang Lv ◽  
Wenyue Jiang ◽  
Lihui Si ◽  
Baojian Liao ◽  
...  

Abstract BackgroundOsteoarthritis (OA) is one of the most common joint diseases and a major public health concern. Current therapies for OA can relieve symptoms but offer no potential for cartilage regeneration. Mesenchymal stem cells (MSCs) have been widely used for the treatment of OA owing to their paracrine secretion of trophic factors, a phenomenon in which exosomes may play a major role. Here, we investigated the potential of exosomes from human umbilical cord-derived MSCs (hUC-MSCs-Exos) at alleviating OA.MethodshUC-MSCs were isolated, cultured, and identified based on the expression of MSC markers and multipotency differentiation. hUC-MSCs-Exos were harvested from hUC-MSC conditioned medium using a sequential centrifugation method. Transmission electron microscopy, dynamic light scattering, flow cytometry, and western blotting were used to identify the exosomes. The effects of hUC-MSCs-Exos on the proliferation and migration of human chondrocytes were evaluated using the cell counting kit-8, EdU-555 cell proliferation kit, and transwell assays. Annexin V-FITC/PI staining and flow cytometry were used to evaluate the effect of exosomes on chondrocyte apoptosis. An in vitro model of human articular chondrocytes treated with interleukin 1 beta (IL-1β) was used to evaluate the effects of exosomes; analyses involved using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting. The role of exosomes in macrophage polarization was examined in the monocyte cell line, THP-1. Rats with surgically induced OA (ACLT+pMMx method) were intra-articularly injected with hUC-MSCs-Exos. The efficacy of exosome injections was assessed using hematoxylin and eosin and safranin-O and fast green staining, and immunohistochemistry.ResultsWe confirmed the superior efficacy of hUC-MSCs-Exos at promoting chondrocyte proliferation and migration and inhibiting chondrocyte apoptosis. Additionally, hUC-MSCs-Exos reversed IL-1β-induced injury in vitro. hUC-MSCs-Exos could inhibit the secretion of pro-inflammatory factors, promote the expression of anti-inflammatory factors, and regulate the polarization of macrophages. hUC-MSCs-Exos attenuated the progression of OA and prevented severe damage to the knee articular cartilage in the rat OA model. ConclusionshUC-MSCs-Exos exerted immunomodulatory and therapeutic effects in a rat model of OA. These exosomes derived from hUC-MSCs can potentially serve as treatments for OA.

2018 ◽  
Vol 373 (2) ◽  
pp. 379-393 ◽  
Author(s):  
Tao Zhang ◽  
Pan Wang ◽  
Yanxia Liu ◽  
Jiankang Zhou ◽  
Zhenqing Shi ◽  
...  

2016 ◽  
Vol 308 (7) ◽  
pp. 511-520 ◽  
Author(s):  
Talita Stessuk ◽  
Maria Beatriz Puzzi ◽  
Elinton Adami Chaim ◽  
Paulo César Martins Alves ◽  
Erich Vinicius de Paula ◽  
...  

2016 ◽  
Vol 38 (1) ◽  
pp. 401-414 ◽  
Author(s):  
Wei Wang ◽  
Xueyong Liu ◽  
Wei Wang ◽  
Jinghua Li ◽  
Yuanyuan Li ◽  
...  

Background/Aims: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. Methods: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated β-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. Results: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. Conclusion: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.


2018 ◽  
Vol 46 (1) ◽  
pp. 279-290 ◽  
Author(s):  
Dongye Yi ◽  
Wei Xiang ◽  
Qing Zhang ◽  
Yongcun Cen ◽  
Qing Su ◽  
...  

Background/Aims: Tumor vascular formation and maintenance are crucial events in glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to differentiate into pericytes and contribute to neovascularization in the glioma microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb-MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that are more active in glioma vascularization. However, the functions of gb-MSCs and the microRNA (miRNA) modifications in the glioblastoma microenvironment have not yet been fully elucidated. Here, we focus on the pericyte differentiation potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular formation and glioblastoma growth. Methods: In vitro, surface markers of gb-MSCs were detected by flow cytometry; the differentiation potential was evaluated by Oil Red O staining, Alizarin Red staining and Alcian blue staining; the proliferation and migration of gb-MSCs in different conditioned media were analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to pericyte transition was detected by immunofluorescence staining and western blot assay; angiogenetic capacity was analyzed by tube formation assay; and levels of cytokines in different supernatant were determined by ELISA. Additionally, RNA was isolated from gb-MSCs, and miRNA modifications were analyzed using the RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned medium increased gb-MSC proliferation and migration and was capable of inducing gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more tube-like structures, and these cells also adhered to tube-like vessels formed by human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor vascular structure in vitro. miRNA expression were also modified in gb-MSCs cultured in malignant glioblastoma-conditioned medium in vitro. Conclusion: These results provide new insight into the functional effects of a subpopulation of MSCs in glioblastoma and may help in the development of novel therapies for solid tumors.


2021 ◽  
Vol 30 ◽  
pp. 096368972199377
Author(s):  
Rui Zhang ◽  
Qiaoxia Zhang ◽  
Zhiyu Zou ◽  
Zheng Li ◽  
Meng Jin ◽  
...  

Mesenchymal stem cells derived from bone marrows (BMSCs) and curcumin derived from turmeric were used for osteoarthritis (OA) treatment, respectively. We invested the effects of curcumin supplementation for BMSC therapeutic effects. In vitro, rat BMSCs were identified by dual-immunofluorescent staining of CD44 and CD90, and flow cytometry. Primary articular chondrocytes were identified by toluidine blue staining and immunofluorescent staining of Col2a1. EdU incorporation, migration assay, real-time quantitative polymerase chain reaction, and Western blot analyses were performed to evaluate the alterations of chondrocytes cocultured with BMSCs. In vivo, the rat model of OA was established by monoiodoacetic acid. After intra-articular injection of allogeneic BMSCs, articular cartilage damage and OA progression were evaluated by histological staining, and Osteoarthritis Research Society International and Mankin score evaluation. Although curcumin alone did not improve cell viability of primary articular chondrocytes, it promoted proliferation and migration of chondrocytes when cocultured with BMSCs. Meanwhile, the expression of anabolic genes in chondrocytes was remarkably increased both at mRNA and protein levels. In OA rats, curcumin and BMSCs cooperated to greatly promote articular cartilage repair and retard OA progression. Therefore, curcumin supplementation enhanced the BMSC function for the proliferation and migration of articular chondrocytes, and anabolic gene expression of extracellular matrix in articular chondrocytes in vitro, and the generation of articular cartilage in vivo. Our study shed light on the potential clinical application of curcumin cooperated with BMSCs in cartilage repair for OA treatment.


2019 ◽  
Vol 52 (1) ◽  
pp. 36
Author(s):  
Nike Hendrijantini

Background: Mesenchymal stem cells (MSCs) and scaffold combination constitute a promising approach currently adopted for tissue engineering. Umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are easily obtained and non-invasive. Gelatine and alginate constitute a biocompatible natural polymer scaffold. At present, a cytotoxicity comparison of gelatine and alginate to hUC-MSCs is not widely conducted Purpose: This study aimed to compare the cytotoxicity of gelatine and alginate in hUC-MSCs in vitro. Methods: Isolation and culture were performed on hUC-MSCs derived from healthy full-term neonates. Flow Cytometry CD90, CD105 and CD73 phenotype characterization was performed in passage 4. 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay was performed to measure the cytotoxicity. The three sample groups were: (T1) hUC-MSCs with α-MEM (alpha-minimum essential medium) solution as control; (T2) hUC-MSCs with gelatine; (T3) hUC-MSCs with alginate Results: Flow cytometry of hUC-MSCs displayed positive CD90, CD105 and CD73 surface markers. Gelatine and alginate had no effect on the viability of hUC-MSCs and no statistically significant difference (p>0.05) of cytotoxicity between gelatine and alginate to hUC-MSCs. Conclusion: Gelatine and alginate proved to be non-toxic to hUC-MSCs in vitro.


2014 ◽  
Vol 2014 ◽  
pp. 1-7
Author(s):  
Syed A. Jamal ◽  
Qiang Ye

Collective movement of cells that have been delivered on biomaterials for transplantation purposes would be a desirable attribute that would promote wound healing, cell proliferation, and eventual growth and regeneration of damaged organs. We hypothesized that colloidal gels made from hydroxyapatite (HA) and poly(D,L-lactic-co-glycolic acid) (PLGA) particles will be conducive to the growth and migration of porcine chondrocytes, will allow the adhesion of human umbilical cord mesenchymal stem cells, and will have negligible effects on the cell cycle of these cells. Then, we performed experiments designed to assess the viability and migratory properties of porcine chondrocytes studded on nanosized HA/PLGA particles. Our experiments show that porcine chondrocytes migrated in and around a hydroxyapatite-based biomaterial that could be described as a colloidal gel. Cells in the colloidal gel demonstrated unidirectional movement. Cells were seen to be extending lamellae and were followed by other cells.


Sign in / Sign up

Export Citation Format

Share Document