Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Ji, Yue; Zhou, Yang; Han, Zhibo; Meng, Lingjun; Liang, Lu; Feng, Xiao; Yang, Shangda; Cheng, Ying; Chen, Dan Dan; Wang, You Wei; Han, Zhong Chao

doi:10.1159/000343340

Cited by 34 publications

(31 citation statements)

References 46 publications

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“…Previous studies have shown that MSCs inhibit Th2-mediated allergic airway inflammation by promoting IFN-γ and TGF-β and regulating Th cell differentiation323334. MSCs are also known to modulate B-cell function35. Macrophages, which are the predominant immune effector cells, act as mediators of the inflammatory response and contribute to both the initiation and resolution of inflammation36.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways

Lin

et al. 2015

Sci Rep

129

113

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Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD). Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism. We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages. In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks. Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages. In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK. Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways. This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways

Lin

et al. 2015

Sci Rep

129

113

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“…MSCs from different perinatal sources have been shown to suppress T cell proliferation [54,58]. In contrast, interactions of perinatal MSCs with other cell types of the innate and adaptive immune systems are largely unknown with only limited number of reports available [59][60][61]. Results from studies comparing inhibitory effects of adult and perinatal MSCs on T cell proliferation are controversial.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cell Characteristics Vary Depending on Their Origin

Wegmeyer

Bröske²,

Leddin³

et al. 2013

Stem Cells and Development

186

161

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Mesenchymal stromal cells (MSCs) are rare progenitor cells that can be isolated from various tissues. They exhibit multilineage differentiation potential, support regenerative processes, and interact with various immune cells. Therefore, MSCs represent a promising tool for regenerative medicine. However, source-dependent and donor-dependent differences of MSC properties, including implications on their clinical application are still largely unknown. We evaluated MSCs derived from perinatal tissues umbilical cord (UC) and amniotic membrane (AM) in comparison to adult MSCs from bone marrow (BM), which were used as gold standard. We found genetic background-independent differences between MSCs from UC and AM. While AM-and UC-MSCs were closer to each other than to BM-MSCs, they also exhibited differences between each other. AM-MSCs from different donors but not UC-MSCs displayed high interdonor variability. In addition, we show that although all MSCs expressed similar surface markers, MSC populations from UC and AM showed differential profiles of gene expression and paracrine factor secretion to BM-derived MSCs. Notably, pathway analysis of gene expression data revealed intriguing differences between MSCs suggesting that MSCs from UC and AM possess in general a higher potential of immunomodulatory capacity, whereas BM-MSCs showed a higher potential of supporting regenerative processes as exemplified by neuronal differentiation and development. These differences between perinatal and BM-derived MSCs may be relevant for clinical applications.

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“…For example, MSCs suppress T-cell proliferation, shift Th1 cells toward Th2 cells [12], and inhibit differentiation of the Th17 subtype of CD4 + T cells [27]. Furthermore, MSCs support the proliferation and terminal differentiation of B cells [28]. MSCs significantly inhibit Th1 cell secretion of IFN-γ and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Han

Liu³

et al. 2014

Cell Physiol Biochem

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Background: Mesenchymal stem cells are capable of self-renewal and multi-lineage differentiation. They are used extensively to treat several diseases. Traditionally, mesenchymal stem cells are cultured in serum-containing media, typically supplemented with fetal bovine serum (FBS). However, the variability of FBS is likely to skew experimental results. Although serum-free media used to expand mesenchymal stem cells has facilitated remarkable achievements, immunomodulation of these cells in under serum-free conditions is poorly understood. We hypothesized that mesenchymal stem cells expanded in serum-free media will retain powerful immunoregulatory functions in vitro and in vivo. Design and Methods: Immunosuppressive activity and the immunomodulatory cytokines produced by mesenchymal stem cells in serum-free media were characterized in vitro. Immunomodulation by serum-free mesenchymal stem cell expansion in monocrotaline-induced pulmonary hypertension was explored in vivo. Results: Similar to cells in serum-containing media, mesenchymal stem cells expanded in serum-free media inhibited proliferation and apoptosis of CD4⁺T cells. They also exhibited strong immunosuppressive activities and secreted high levels of immunomodulatory cytokines such as PGE2, IDO1, COX2, IL-6, and IL-1β, but not HGF. On the other hand, growth of mesenchymal stem cells in serum-free media attenuated pulmonary vascular remodeling and inhibited mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-1β, and IL-18. Conclusions: Mesenchymal stem cells in serum-free media maintained powerful immunomodulatory function in vitro and in vivo; serum-free media may replace serum-containing media for basic research and clinical applications.

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Mesenchymal Stem Cells Support Proliferation and Terminal Differentiation of B Cells

Cited by 34 publications

References 46 publications

Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways

Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways

Mesenchymal Stromal Cell Characteristics Vary Depending on Their Origin

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

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