scholarly journals Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0202590 ◽  
Author(s):  
Fernando Laso-García ◽  
Jaime Ramos-Cejudo ◽  
Francisco Javier Carrillo-Salinas ◽  
Laura Otero-Ortega ◽  
Ana Feliú ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Progressive Multiple Sclerosis

Extracellular vesicles from three dimensional culture of human placental mesenchymal stem cells ameliorated renal ischemia/reperfusion injury

2021 ◽  
pp. 039139882098680
Author(s):  
Xuefeng Zhang ◽  
Nan Wang ◽  
Yuhua Huang ◽  
Yan Li ◽  
Gang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Three Dimensional ◽  
3D Culture ◽  
Placental Mesenchymal Stem Cells ◽  
2D And 3D

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.

scholarly journals Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daphne Hingert ◽  
Karin Ekström ◽  
Jonathan Aldridge ◽  
Rosella Crescitelli ◽  
Helena Brisby
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Human Mesenchymal Stem Cells ◽  
Invasive Treatment ◽  
Disc Cells ◽  
Apoptotic Activity

Abstract Background Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods hMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 × 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions. Results The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs. Conclusion hMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.

scholarly journals Ex VivoExpansion of Human Mesenchymal Stem Cells in Defined Serum-Free Media

2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Sunghoon Jung ◽  
Krishna M. Panchalingam ◽  
Lawrence Rosenberg ◽  
Leo A. Behie
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Culture Media ◽  
Human Mesenchymal Stem Cells ◽  
Efficient Production ◽  
Serum Free ◽  
Medium Development ◽  
Current Cell ◽  
Free Media

Human mesenchymal stem cells (hMSCs) are presently being evaluated for their therapeutic potential in clinical studies to treat various diseases, disorders, and injuries. To date, early-phase studies have indicated that the use of both autologous and allogeneic hMSCs appear to be safe; however, efficacy has not been demonstrated in recent late-stage clinical trials. Optimized cell bioprocessing protocols may enhance the efficacy as well as safety of hMSC therapeutics. Classical media used for generating hMSCs are typically supplemented with ill-defined supplements such as fetal bovine serum (FBS) or human-sourced alternatives. Ideally, culture media are desired to have well-defined serum-free formulations that support the efficient production of hMSCs while maintaining their therapeutic and differentiation capacity. Towards this objective, we review here current cell culture media for hMSCs and discuss medium development strategies.

scholarly journals Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

2011 ◽  
Vol 11 (9) ◽  
pp. 1295-1303 ◽  
Author(s):  
Peter J Darlington ◽  
Marie-Noëlle Boivin ◽  
Amit Bar-Or
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential

scholarly journals Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction

2021 ◽  
Vol 9 ◽  
Author(s):  
Thora Bjorg Sigmarsdottir ◽  
Sarah McGarrity ◽  
James T. Yurkovich ◽  
Óttar Rolfsson ◽  
Ólafur Eysteinn Sigurjónsson
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Cell Lineage ◽  
Human Mesenchymal Stem Cells ◽  
Metabolic Model ◽  
Metabolic Function ◽  
Metabolic States ◽  
Initial Discovery ◽  
Genome Scale

Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs.

scholarly journals The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huifang Li ◽  
Haoyan Huang ◽  
Xiaoniao Chen ◽  
Shang Chen ◽  
Lu Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Apoptosis ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Self Healing ◽  
Placental Mesenchymal Stem Cells ◽  
Therapy Effect ◽  
Microrna Sequencing

Abstract Background Chemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear. Methods Doxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing. Results MSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis. Conclusions Hsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.

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