Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs

Weiss, Andreas; Dahlke, Marc H.

doi:10.3389/fimmu.2019.01191

Cited by 556 publications

(469 citation statements)

References 109 publications

Supporting

Mentioning

449

Contrasting

Unclassified

Order By: Relevance

“…These ndings emphasize the importance of apoptosis in MSC-mediated immunomodulation and might explain previous study results, in which apoptotic MSCs (apoMSCs) were shown to be superior compared to living MSCs [8][9][10]. Besides, numerous studies recently revealed that apoptotic cells release not only apoptotic bodies but also a range of extracellular vesicles (Evs) that can act as biological modulators.…”

supporting

confidence: 64%

See 1 more Smart Citation

Ex vivo Inducing Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure

Morimoto

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Apoptosis was reported to take crucial role in mesenchymal stem cell (MSC)-mediated immunomodulation, in which apoptotic MSCs were shown to be superior compared to living MSCs. Furthermore, extracellular vesicles (Evs) derived from MSCs were revealed more specific advantages for patient safety such as lower propensity to trigger innate and adaptive immune responses. As a safety and simple operation, high hydrostatic pressure (HHP), a physical technique that uses only fluid pressure to inactivate cells or tissues, has been developed and applied in a lot of field of biosciences, including biotechnology, biomaterials, or tissue engineering. Methods: MSCs isolated from human bone marrow were suspended cultured in appropriate medium and subjected to pressurization at 50 MPa for 36 h. Then cells were collected and investigated apoptotic pathway by transmission electron microscopy (TEM), phosphatidylserine membrane translocations, cleaved caspase-3/7 and terminal deoxy-nucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Besides, viability assays and live cell imaging were also used for assessement of cell survival after pressurization. Results: We found that HHP at 50 MPa for ≥36 h completely induced MSC death by Live/Dead assay, live cell imaging and WST-8 assay up to 7 days after pressurization. The large amount of apoptotic MSCs death was found based on morphological changes in TEM, phosphatidylserine exposure, caspase activation and detection of DNA fragmentations via TUNEL staining. Conclusions: In the current study, our data revealed that HHP treatment was convenient processing which safety and effectively induced MSCs undergo apoptosis. Especially, by capable of manufacture expanding, this technique might provide numbers of manipulated products using for industrial cell-based therapies.

show abstract

supporting

confidence: 64%

“…MSCs have no active cell metabolism, it can be assumed that they do not differentiate into CAF-like cells with the corresponding secretion of growth factors, cytokines, and chemokines [6,10]. Notably, dead…”

mentioning

confidence: 99%

Ex vivo Inducing Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure

Morimoto

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…We revealed that only MSCs are able to suppress the granzyme B‐mediated cytotoxic CD8 + T‐cell response, which is known as one of the principal mediators of acute allograft rejection . MSCs have been shown to suppress T‐cell proliferation and shift the effector functions of T‐cells toward regulatory functions, mainly through the expression of immunomodulatory molecules such as IDO, and secretion of prostaglandin‐E2 (PGE2), nitric oxide, and TGF‐β . Lacking metabolic and secretory activity, HI‐MSCs have no T‐cell suppressive effect, which makes them incapable of prolonging allograft survival in vivo.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation

Weiss

Lee

Eggenhofer³

et al. 2020

Stem Cells

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC-induced immunomodulation is known to be mediated through both MSC-secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated MSCs (HI-MSCs) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC.To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI-MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 mice to BALB/c recipients. MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-MSC had no effect on graft survival. We revealed that control MSC dose-dependently inhibited CD3 + and CD8 + T-cell proliferation in vitro, whereas HI-MSC had no effect. In the second model, sepsis was induced in mice via cecal ligation and puncture. HI-MSC treatment significantly improved the overall survival, whereas control MSCs had no effect. in vitro studies demonstrated that HI-MSCs are more effectively phagocytosed by monocytes than control MSCs and induced cell death in particular of activated CD16 + monocytes, which may explain the immune protective effect of HI-MSC in the sepsis model. The results of our study demonstrate that MSC-mediated immunomodulation in sepsis is dependent on a passive recognition of MSC by monocytes, whereas fully functional MSCs are required for inhibition of T-cell-mediated allograft rejection. K E Y W O R D S heat-inactivated mesenchymal stem

show abstract

“…Proposed interaction of MSCs with host immune cells and released cytocines; Data obtained from[33,34], The figure is made with biorender (https://biorender. com/)…”

mentioning

confidence: 99%

Mesenchymal Stem Cell Therapy for COVID-19: Present or Future

Golchin

Seyedjafari

Ardeshirylajimi

2020

Stem Cell Rev and Rep

304

302

View full text Add to dashboard Cite

" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.

show abstract

Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs

Cited by 556 publications

References 109 publications

Ex vivo Inducing Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure

Ex vivo Inducing Apoptotic Mesenchymal Stem Cell by High Hydrostatic Pressure

Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation

Mesenchymal Stem Cell Therapy for COVID-19: Present or Future

Contact Info

Product

Resources

About