Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential

Song, Na; Scholtemeijer, Martijn; Shah, Khalid

doi:10.1016/j.tips.2020.06.009

Cited by 426 publications

(334 citation statements)

References 101 publications

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“…MSCs are a group of adult stem cells with self-renewal and differentiation abilities and also immunomodulatory properties, and have been widely used in tissue repair and regeneration 68 . They express CD73, CD90, and CD105, and don't express CD45, CD34, CD14, CD19, CD11b, and human leukocyte antigen DR isotype 69 .…”

Section: Immune Cell-derived Exosomes In Immunomodulation After Amimentioning

confidence: 99%

The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction

Xiong¹,

Gong²,

Tang³

et al. 2021

Theranostics

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Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molecular and cellular basis are urgently needed. Exosomes are a type of extracellular vesicles which contain a large amount of biologically active substances, like lipids, nucleic acids, proteins and so on. Emerging evidence suggests key roles of exosomes in immune regulation post AMI. A variety of immune cells participate in the immunomodulation after AMI, working together to clean up necrotic tissue and repair damaged myocardium. Stem cell therapy for myocardial infarction has long been a research hotspot during the last two decades and exosomes secreted by stem cells are important active substances and have similar therapeutic effects of immunomodulation, anti-apoptosis, anti-fibrotic and angiogenesis to those of stem cells themselves. Therefore, in this review, we focus on the characteristics and roles of exosomes produced by both of endogenous immune cells and exogenous stem cells in myocardial repair through immunomodulation after AMI.

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Section: Immune Cell-derived Exosomes In Immunomodulation After Amimentioning

confidence: 99%

The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction

Xiong¹,

Gong²,

Tang³

et al. 2021

Theranostics

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“…Moreover, MSCs have been recognized for their immunomodulatory potential. [45][46][47] Therefore, the antiinflammatory action exerted by MSCs on local renal tissues might also contribute to the improved kidney function. 48,49 Further work is necessary to elucidate the detailed mechanisms among the engrafted podocytes and MSCs as well as the host glomeruli and renal inflammatory microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Injection of hybrid 3D spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells into the renal cortex improves kidney function and replenishes glomerular podocytes

Yang

Chen

Jhuang

et al. 2021

Bioengineering & Transla Med

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Podocytes are highly differentiated epithelial cells that are crucial for maintaining the glomerular filtration barrier in the kidney. Podocyte injury followed by depletion is the major cause of pathological progression of kidney diseases. Although cell therapy has been considered a promising alternative approach to kidney transplantation for the treatment of kidney injury, the resultant therapeutic efficacy in terms of improved renal function is limited, possibly owing to significant loss of engrafted cells. Herein, hybrid three-dimensional (3D) cell spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells were designed to mimic the glomerular microenvironment and as a cell delivery vehicle to replenish the podocyte population by cell transplantation. After creating a native glomerulus-like condition, the expression of multiple genes encoding growth factors and basement membrane factors that are strongly associated with podocyte maturation and functionality was significantly enhanced. Our in vivo results demonstrated that intrarenal transplantation of podocytes in the form of hybrid 3D cell spheroids improved engraftment efficiency and replenished glomerular podocytes. Moreover, the proteinuria of the experimental mice with hypertensive nephropathy was effectively reduced. These data clearly demonstrated the potential of hybrid 3D cell spheroids for repairing injured kidneys.

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“…Another MSC feature relevant for therapy is represented by their immunosuppressive potential, as reviewed in [ 17 , 48 , 49 ]. In mixed cell cultures of transduced MSC together with allogeneic splenocytes, the cells directly interact through cell-to-cell contact, but also communicate through signaling molecules such as cytokines, including transforming growth factor-β (TGF-β), hepatocyte growth factor, and prostaglandin E2, as well as other anti-inflammatory factors [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…MSC represent great vehicles for gene therapy due to their potential to migrate towards diseased tissues such as tumors [ 14 ], the atherosclerotic plaque [ 15 ], or other lesioned tissues such as the ischemic myocardium [ 16 ]. In various experimental therapies, MSC were used as naïve and/or engineered cells [ 8 , 17 ]. Usually, a transgene is inserted in the MSC genome by lentiviral or retroviral transduction, performed with relatively high efficiency, but after insertion in the genome, it is continuously overexpressed.…”

Section: Introductionmentioning

confidence: 99%

K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells

Dumitrescu¹,

Vacaru²,

Trusca³

et al. 2021

IJMS

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Adenoviral vectors are important vehicles for delivering therapeutic genes into mammalian cells. However, the yield of the adenoviral transduction of murine mesenchymal stromal cells (MSC) is low. Here, we aimed to improve the adenoviral transduction efficiency of bone marrow-derived MSC. Our data showed that among all the potential transduction boosters that we tested, the K2 Transfection System (K2TS) greatly increased the transduction efficiency. After optimization of both K2TS components, the yield of the adenoviral transduction increased from 18% to 96% for non-obese diabetic (NOD)-derived MSC, from 30% to 86% for C57BL/6-derived MSC, and from 0.6% to 63% for BALB/c-derived MSC, when 250 transduction units/cell were used. We found that MSC derived from these mouse strains expressed different levels of the coxsackievirus and adenovirus receptors (MSC from C57BL/6≥NOD>>>BALB/c). K2TS did not increase the level of the receptor expression, but desensitized the cells to foreign DNA and facilitated the virus entry into the cell. The expression of Stem cells antigen-1 (Sca-1) and 5′-nucleotidase (CD73) MSC markers, the adipogenic and osteogenic differentiation potential, and the immunosuppressive capacity were preserved after the adenoviral transduction of MSC in the presence of the K2TS. In conclusion, K2TS significantly enhanced the adenoviral transduction of MSC, without interfering with their main characteristics and properties.

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Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential

Cited by 426 publications

References 101 publications

The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction

The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction

Injection of hybrid 3D spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells into the renal cortex improves kidney function and replenishes glomerular podocytes

K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells

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