Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells on Mouse Bone-Marrow-Derived Dendritic Cells

Mesenchymal stem cells (MSCs) are considered valuable sources for cell therapy because of their immune regulatory function. Here, we investigated the effects of tonsil-derived MSCs (T-MSCs) on the differentiation, maturation, and function of dendritic cells (DCs). We examined the effect of T-MSCs on differentiation and maturation of bone-marrow- (BM-) derived monocytes into DCs and we found suppressive effect of T-MSCs on DCs via direct contact as well as soluble mediators. Moreover, T cell proliferation, normally increased in the presence of DCs, was inhibited by T-MSCs. Differentiation of CD4+T cell subsets by the DC-T cell interaction also was inhibited by T-MSCs. The soluble mediators suppressed by T-MSCs were granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Taken together, T-MSCs exert immune modulatory function via suppression of the differentiation, maturation, and function of BM-derived DCs. Our data suggests that T-MSCs could be used as a novel source of stem cell therapy as immune modulators.

Download Full-text

Corrigendum to “Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells on Mouse Bone-Marrow-Derived Dendritic Cells”

Stem Cells International ◽

10.1155/2019/9071046 ◽

2019 ◽

Vol 2019 ◽

pp. 1-1

Author(s):

Minhwa Park ◽

Yu-Hee Kim ◽

Jung-Hwa Ryu ◽

So-Youn Woo ◽

Kyung-Ha Ryu

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Dendritic Cells ◽

Mouse Bone Marrow

Download Full-text

Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1488-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 16

Author(s):

Zhonghua Lu ◽

Wei Chang ◽

Shanshan Meng ◽

Xiuping Xu ◽

Jianfeng Xie ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Dendritic Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Akt Pathway ◽

Mouse Bone Marrow ◽

Akt Inhibitor ◽

Hepatocyte Growth

Abstract Background Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway. Methods MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice. Results Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the differentiation of mDCs into regulatory DCs characterized by low expression of MHCII, CD86, and CD40 molecules, strong phagocytic function, and the ability to inhibit T cell proliferation. The effect of MSCs on DCregs was enhanced with the increase in HGF secretion and was weakened with the decrease in HGF secretion. DCregs induced by recombinant HGF were attenuated by the Akt inhibitor MK-2206. Lung DC aggregation and mDC ratio increased in LPS-induced ALI mice, while treatment with MSCs decreased lung DC aggregation and maturation and alleviated lung pathological injury. High expression of the HGF gene enhanced the above effect of MSCs, while decreased expression of HGF weakened the above effect of MSCs. Conclusions MSCs alleviate early ALI via paracrine HGF by inducing mDCs to differentiate into regulatory DCs. Furthermore, the mechanism of HGF-induced differentiation of mDCs into DCregs is related to the activation of the Akt pathway.

Download Full-text

Mouse Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Perinatal Brain Injury Via a CD8+ T Cell Mechanism in a Model of Intrauterine Inflammation

Reproductive Sciences ◽

10.1007/s43032-020-00157-y ◽

2020 ◽

Vol 27 (7) ◽

pp. 1465-1476

Author(s):

Hongxi Zhao ◽

Li Xie ◽

Julia L. Clemens ◽

Lu Zong ◽

Michael W. McLane ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Brain Injury ◽

T Cell ◽

Cd8 T Cell ◽

Mouse Bone Marrow ◽

Perinatal Brain Injury

Download Full-text

Bone Marrow Mesenchymal Stem Cells Inhibit the Function of Dendritic Cells by Secreting Galectin-1

BioMed Research International ◽

10.1155/2017/3248605 ◽

2017 ◽

Vol 2017 ◽

pp. 1-19 ◽

Cited By ~ 7

Author(s):

Yue Zhang ◽

Xia-hui Ge ◽

Xue-Jun Guo ◽

Si-bin Guan ◽

Xiao-ming Li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

T Cells ◽

Mesenchymal Stem Cells ◽

Dendritic Cells ◽

Mapk Pathway ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Mouse Bone Marrow

This study aimed to investigate whether bone marrow-derived mesenchymal stem cells (BM-MSCs) can inhibit function of dendritic cells (DCs) by secreting Galectin-1 (Gal-1). BM-MSCs have been shown to inhibit the maturation and function of DCs, further inhibiting the activation and proliferation of T cells. However, the detailed mechanism remains unknown. In this current study, MSCs and DCs derived from mouse bone marrow were cocultured using Transwell culture plates under different in vitro conditions. The results showed that as the ratio of MSC to DC of the coculture system increased and the coculture time of the two cells prolonged, the concentrations of Gal-1, interleukin- (IL-) 10, and IL-12 in the supernatants were increased and the protein expression of Gal-1 on and within DCs was also enhanced. The phosphorylation of extracellular signal-regulated kinase (ERK) pathway in DCs was boosted, whereas p38 mitogen-activated protein kinase (MAPK) pathway phosphorylation was weakened. Meanwhile, the expression of costimulatory molecules on the surface of DCs was decreased, and the proliferative effect of DCs on allogeneic T cells was also decreased. Therefore, this present study indicated that Gal-1 secreted from MSCs upregulated expression of Gal-1 and stimulated formation of tolerance immunophenotype on DCs, where the underlying mechanism was the regulation of the MAPK signaling pathway in DCs, thereby inhibiting the function of DCs.

Download Full-text

Murine Bone Marrow Mesenchymal Stem Cells Cause Mature Dendritic Cells to Promote T-Cell Tolerance

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.2008.02180.x ◽

2008 ◽

Vol 68 (6) ◽

pp. 607-615 ◽

Cited By ~ 39

Author(s):

Q. Wang ◽

B. Sun ◽

D. Wang ◽

Y. Ji ◽

Q. Kong ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Dendritic Cells ◽

T Cell ◽

T Cell Tolerance ◽

Cell Tolerance ◽

Murine Bone Marrow ◽

Marrow Mesenchymal Stem Cells

Download Full-text

Differentiation of Mouse Bone-Marrow Mesenchymal Stem Cells into Motor Neuron Cells in vitro

Journal of Al-Nahrain University-Science ◽

10.22401/jnus.19.2.14 ◽

2016 ◽

Vol 19 (2) ◽

pp. 111-116

Author(s):

Rafal Hussamildeen Abdullah ◽

◽

Shahlla Mahdi Salih ◽

Nahi Yosef Yaseen ◽

Ahmed Majeed Al-Shammari ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Motor Neuron ◽

Mouse Bone Marrow ◽

Marrow Mesenchymal Stem Cells

Download Full-text

Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02110-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pegah Nammian ◽

Seyedeh-Leili Asadi-Yousefabad ◽

Sajad Daneshi ◽

Mohammad Hasan Sheikhha ◽

Seyed Mohammad Bagher Tabei ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Cell Therapy ◽

Femoral Artery ◽

Critical Limb Ischemia ◽

Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Download Full-text

Uncarboxylated osteocalcin alleviates the inhibitory effect of high glucose on osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by regulating TP63

BMC Molecular and Cell Biology ◽

10.1186/s12860-021-00365-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Fangzi Gong ◽

Le Gao ◽

Luyao Ma ◽

Guangxin Li ◽

Jianhong Yang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

High Glucose ◽

Bone Development ◽

Inhibitory Effect ◽

Osteoblastic Differentiation ◽

Diabetic Patients ◽

Mouse Bone Marrow

Abstract Background Progressive population aging has contributed to the increased global prevalence of diabetes and osteoporosis. Inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by hyperglycemia is a potential pathogenetic mechanism of osteoporosis in diabetic patients. Uncarboxylated osteocalcin (GluOC), a protein secreted by mature osteoblasts, regulates bone development as well as glucose and lipid metabolism. In our previous studies, GluOC was shown to promote osteoblastic differentiation of BMSCs; however, the underlying mechanisms are not well characterized. Tumor protein 63 (TP63), as a transcription factor, is closely related to bone development and glucose metabolism. Results In this study, we verified that high glucose suppressed osteogenesis and upregulated adipogenesis in BMSCs, while GluOC alleviated this phenomenon. In addition, high glucose enhanced TP63 expression while GluOC diminished it. Knock-down of TP63 by siRNA transfection restored the inhibitory effect of high glucose on osteogenic differentiation. Furthermore, we detected the downstream signaling pathway PTEN/Akt/GSK3β. We found that diminishing TP63 decreased PTEN expression and promoted the phosphorylation of Akt and GSK3β. We then applied the activator and inhibitor of Akt, and concluded that PTEN/Akt/GSK3β participated in regulating the differentiation of BMSCs. Conclusions Our results indicate that GluOC reduces the inhibitory effect of high glucose on osteoblast differentiation by regulating the TP63/PTEN/Akt/GSK3β pathway. TP63 is a potential novel target for the prevention and treatment of diabetic osteoporosis.

Download Full-text