Mechanism of action of mesenchymal stem cells (MSCs): Impact of Delivery Method

Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.

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Mesenchymal Stem Cells in Rat Hepatic Fibrosis MModel: Benefits? Mechanism of Action?: 2017 Presidential Poster Award

The American Journal of Gastroenterology ◽

10.14309/00000434-201710001-00929 ◽

2017 ◽

Vol 112 ◽

pp. S521

Author(s):

Deniz Guney Duman ◽

Umit Mustafa Ugurlu ◽

Noushin Zibandeh ◽

Tolga Akkoc ◽

Munkhtsetseg Banzragch ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Hepatic Fibrosis ◽

Mechanism Of Action ◽

Poster Award

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Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

Stem Cells International ◽

10.1155/2015/421253 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 8

Author(s):

Peter Succar ◽

Edmond J. Breen ◽

Donald Kuah ◽

Benjamin R. Herbert

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Disease Progression ◽

Proinflammatory Cytokines ◽

Mechanism Of Action ◽

Stromal Vascular Fraction ◽

Slow Disease Progression

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc)in vitroand measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1αdecreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation usingin vivomodels.

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Allogeneic Gene-Modified Mesenchymal Stem Cells for Stable Stroke: Mechanism of Action and Translation to the Clinic (IN8-2.004)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.in8-2.004 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. IN8-2.004-IN8-2.004

Author(s):

C. Case

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mechanism Of Action ◽

Stroke Mechanism

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Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action

Molecular Medicine Reports ◽

10.3892/mmr.2020.11422 ◽

2020 ◽

Author(s):

Mengyi Jiang ◽

Xuemei Wang ◽

Pin Wang ◽

Wei Peng ◽

Bo Zhang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Mechanism Of Action ◽

Marrow Mesenchymal Stem Cells

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Allogeneic Gene-Modified Mesenchymal Stem Cells for Stable Stroke: Mechanism of Action and Translation to the Clinic (S53.003)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.s53.003 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. S53.003-S53.003

Author(s):

C. Case

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mechanism Of Action ◽

Stroke Mechanism

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Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and demonstrates anti-inflammatory mechanism of action

10.1101/571976 ◽

2019 ◽

Author(s):

Amanda M. Hamilton ◽

Wing-Yee Cheung ◽

Alejandro Gómez-Aristizábal ◽

Sayaka Nakamura ◽

Amélie Chaboureau ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Prussian Blue ◽

Mechanism Of Action ◽

Cartilage Damage ◽

Joint Inflammation ◽

Knee Joints ◽

Iron Oxide Nanoparticle ◽

Saline Control ◽

Post Surgery

AbstractOsteoarthritis (OA) is characterized by cartilage degradation and chronic joint inflammation. Mesenchymal stem cells (MSCs) have shown promising results in OA, but their mechanism of action is not fully understood. We hypothesize that MSCs polarize macrophages, which are strongly associated with joint inflammation to more homeostatic sub-types. We tracked ferumoxytol (Feraheme™, iron oxide nanoparticle)-labeled murine MSCs (Fe-MSCs) in murine OA joints, and quantified changes to homeostatic macrophages.10-week-old C57BL/6 male mice (n=5/group) were induced to undergo osteoarthritis by destabilization of medical meniscus (DMM) or sham surgery. 3 weeks post-surgery, mice were injected intra-articularly with either fluorescent dye-(DiR) labeled or DiR+ferumoxytol-labeled (DiR+Fe) bone marrow mesenchymal stem cells (MSC, 50×103MSCs/mouse) or saline (control), to yield 4 groups (n=5 per group for each timepoint [1, 2 and 4weeks]): i) DMM+Saline; ii) DMM+DiR+Fe-MSC; iii) DMM+DiR MSC; iv) SHAM+DiR+Fe-MSC and saline in contralateral knee. 4 weeks after injection, mice were imaged by MRI, and scored for i) OARSI to determine cartilage damage and ii) immunohistochemical changes in CD206, F480 and Prussian Blue/Sca-1 to detect homeostatic macrophages, total macrophages and ferumoxytol-labeled MSCs respectively.Ferumoxytol-labeled MSCs persisted in DMM knee joints at greater levels than in SHAM-MSC knee joints. We observed no difference in OARSI scores between MSC and vehicle groups. Sca-1 and Prussian Blue co-staining confirmed the ferumoxytol label resides in MSCs, although some ferumoxytol label was detected in proximity to MSCs in macrophages, likely due to phagocytosis of apoptotic MSCs, increasing functionality of these macrophages through MSC efferocytosis. We showed decreased MRI synovitis scores in MSC-treated compared to control animals. For the first time we show that MSC-treated OA mice had increased macrophage infiltration (p<0.08) with an increased proportion of CD206+ (homeostatic) macrophages (p<0.01), supporting our hypothesis that MSCs modulate synovial inflammation.

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LncRNA TCONS_00023297 Regulates the Balance of Osteogenic and Adipogenic Differentiation in Bone Marrow Mesenchymal Stem Cells and the Coupling Process of Osteogenesis and Angiogenesis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.697858 ◽

2021 ◽

Vol 9 ◽

Author(s):

Haitao Wang ◽

Peng Wei ◽

Yi Zhang ◽

Yuebai Li ◽

Li Yin

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Mechanism Of Action ◽

Noncoding Rna ◽

Adipogenic Differentiation ◽

Luciferase Reporter ◽

Coupling Process ◽

Marrow Mesenchymal Stem Cells

Long noncoding RNA (lncRNA) is a noncoding RNA with a length of more than 200 bases. It plays an important role in the occurrence and development of diseases. Research on lncRNAs has received increasing attention. Bone is an important organ of the human body. As the population ages, the incidence of osteoporosis gradually increases. The mechanism of action of lncRNAs in the development of osteoporosis is unclear. The imbalance between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells (hBMSCs) and the coupling process of osteogenesis and angiogenesis plays an important role in the development of osteoporosis. Therefore, this study focused on the mechanism by which lncRNAs regulate the osteogenic differentiation of bone marrow mesenchymal stem cells and the mechanism of action of lncRNAs in bone metabolism. The expression of lncRNAs in the osteogenic differentiation of hBMSCs was detected by lncRNA microarray. Real-time quantitative PCR was used to detect the expression changes of lncRNA and osteogenic genes during hBMSC osteogenic and adipogenic differentiation. The ceRNA mechanisms were detected by RIP and luciferase reporter gene assays. The effect of lncRNAs on the osteogenesis–angiogenesis coupling process was detected by Transwell assays. TCONS_00023297 increased expression during osteogenic differentiation; TCONS_00023297 overexpression promoted osteogenic differentiation of hBMSCs; BMP2 regulated TCONS_00023297 expression in a concentration- and time-dependent manner; TCONS_00023297 regulated miR-608 via a ceRNA mechanism; TCONS_00023297 inhibited hBMSC adipogenic differentiation; and TCONS_00023297 promoted VEGF secretion by hBMSCs. TCONS_00023297 regulates osteogenic differentiation, adipogenic differentiation, and osteogenic–angiogenic coupling of hBMSCs via the TCONS_00023297/miR-608/RUNX2/SHH signaling axis.

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