Interaction between Mesenchymal Stem Cells and B-Cells

Fan, Linxiao; Li, Lanjuan; Chen, Jiajia; Cen, Panpan; Wang, Jie; Li, Lanjuan

doi:10.3390/ijms17050650

Cited by 93 publications

(72 citation statements)

References 107 publications

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“…These include age of the donors and possible adverse impact of the disease milieu (e.g. the pro-inflammatory phenotype) (25). Alternatively, preferential response to allo vs. auto hMSCs may reflect enhanced endogenous repair, an important mechanism underlying hMSC cardiorepair (26).…”

Section: Discussionmentioning

confidence: 99%

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

Hare

DiFede

Rieger

et al. 2017

Journal of the American College of Cardiology

298

246

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Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients (age: 55.8 ± 11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov, #NCT01392625. Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: −1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: −47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05). Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results.

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Section: Discussionmentioning

confidence: 99%

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

Hare

DiFede

Rieger

et al. 2017

Journal of the American College of Cardiology

298

246

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“…Therapeutic potential of MSCs in the treatment of acute liver failure has already been well described by us and others. (1,8,9) It is well-known that MSCs promote induction and expansion of Tregs and Bregs, (33)(34)(35)(36)(37)(38)(39) but the impact of these regulatory cells in MSC-mediated attenuation of acute liver failure was unknown. Accordingly, herewith, we described the molecular mechanisms involved in the crosstalk between MSCs and liver regulatory cells during acute liver inflammation.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

et al. 2018

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One of the therapeutic options for the treatment of fulminant hepatitis is repopulation of intrahepatic regulatory cells because their pool is significantly reduced during acute liver failure. Although it is known that mesenchymal stem cells (MSCs), which have beneficent effects in the therapy of fulminant hepatitis, may promote expansion of regulatory T cells (Tregs) and regulatory B cells (Bregs), the role of these regulatory cells in MSC-mediated attenuation of acute liver injury is unknown. Herewith, we described the molecular mechanisms involved in the crosstalk between MSCs and liver regulatory cells and analyzed the potential of MSC-based therapy for the expansion of intrahepatic regulatory cells in mouse model of acute liver failure. MSC-dependent attenuation of α-galactosylceramide (α-GalCer)-induced acute liver injury in mice was accompanied with an increased presence of interleukin (IL) 10-producing CD4 CD25 forkhead box P3 Tregs and IL10- and transforming growth factor β-producing marginal zone-like Bregs in the liver. Depletion of Bregs did not alter MSC-based alleviation of acute liver failure, whereas depletion of Tregs completely abrogated hepatoprotective effects of MSCs and inhibited their capacity to attenuate hepatotoxicity of liver natural killer T cells (NKTs), indicating that Tregs, and not Bregs, were critically involved in MSC-based modulation of acute liver inflammation. MSCs, in a paracrine, indoleamine 2,3-dioxygenase-dependent manner, significantly increased the capacity of Tregs to produce immunosuppressive IL10 and to suppress hepatotoxicity of liver NKTs. Accordingly, adoptive transfer of MSC-primed Tregs resulted in the complete attenuation of α-GalCer-induced acute liver failure. In conclusion, our findings highlighted the crucial importance of Tregs for MSC-based attenuation of acute liver failure and indicated the significance of MSC-mediated priming of Tregs as a new therapeutic approach in Treg-based therapy of acute liver injury. Liver Transplantation 24 687-702 2018 AASLD.

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“…The release of antibodies and other co-stimulatory molecules by B cells is also reduced after MSC administration. However, MSC-B cell interactions are not well understood and probably require both direct cell contact and indirect participation of other immune cells acting as intermediates (Fan et al, 2016). Indeed, CD3+ T cells are required for B-cell inhibition, otherwise the inhibitory effect of MSCs disappears and B cells proliferate (Rosado et al, 2015).…”

Section: Msc Immunomodulation By Cell-cell Contactmentioning

confidence: 99%

Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

Gomez-Salazar

Gonzalez-Galofre

Casamitjana

et al. 2020

Front. Bioeng. Biotechnol.

118

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Mesenchymal stem cells are culture-derived mesodermal progenitors isolatable from all vascularized tissues. In spite of multiple fundamental, pre-clinical and clinical studies, the native identity and role in tissue repair of MSCs have long remained elusive, with MSC selection in vitro from total cell suspensions essentially unchanged as a mere primary culture for half a century. Recent investigations have helped understand the tissue origin of these progenitor cells, and uncover alternative effects of MSCs on tissue healing via growth factor secretion and interaction with the immune system. In this review, we describe current trends in MSC biology and discuss how these may improve the use of these therapeutic cells in tissue engineering and regenerative medicine.

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Interaction between Mesenchymal Stem Cells and B-Cells

Cited by 93 publications

References 107 publications

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

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