Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?

Chen, Q; Shou, Peishun; Zheng, Changwen; Jiang, Meei Jyh; Cao, Guoxin; Yang, Qingling; Chen, Jianjun; Xie, Ningxia; Velletri, Tania; Zhang, X; Xu, Chunsheng; Zhang, L; Yang, Haisong; Hou, Jia; Wang, Y; Shi, Yufang

doi:10.1038/cdd.2015.168

Cited by 959 publications

(809 citation statements)

References 156 publications

(177 reference statements)

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“…Since various cytokines in the microenvironment of the MSC niche are critical for MSC lineage commitment (17, 18), it is possible that the reversion of MSC immunosuppression by IFNα is due to inducing MSC differentiation. To test this possibility, we treated MSCs with IFNγ and TNFα or IFNγ, TNFα and IFNα for 24 hours.…”

Section: Resultsmentioning

confidence: 99%

Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

et al. 2016

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Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that IFNα-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting iNOS (inducible nitric oxide synthase) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from Stat1 homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

et al. 2016

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“…Several fundamental signaling pathways participate in regulating the lineage commitment of MSCs, including transforming growth factor-beta (TGFβ)/bone morphogenic protein (BMP) signaling, wingless type MMTV integration site (Wnt) signaling, Hedgehogs (Hh), Notch, and fibroblast growth factors (FGFs) (31, 32). …”

Section: Mesenchymal Stem Cells or Marrow Stromal Cellsmentioning

confidence: 99%

Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

et al. 2016

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The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions, such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation.

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“…MSCs have many markers [36,37]. To identify the phenotypes of MSCs and MSCs-HO-1, the cell markers CD29, CD90, CD73, CD105, CD34, CD45, CD14, and CD11b were identified by flow cytometry.…”

Section: Phenotypes Of Mscs-ho-1 and Mscsmentioning

confidence: 99%

Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells

Chen

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has therapeutic effects on endothelial damage during acute lung injury (ALI). Heme oxygenase-1 (HO-1) can restore homeostasis and implement cytoprotective defense functions in many pathologic states. Therefore, we explored whether transduction of HO-1 into BM-MSCs (MSCs-HO-1) would have an increased beneficial effect on lipopolysaccharide (LPS)-induced inflammatory and oxidative damage in human pulmonary microvascular endothelial cells (PVECs). Methods: MSCs were isolated from rat bone marrow and transfected with the HO-1 gene by a lentivirus vector. The phenotype and multilineage differentiation of MSCs were assessed. MSCs or MSCs-HO-1 were co-cultured with PVECs using a transwell system, and LPS was added to induce PVEC injury. The production of reactive oxygen species (ROS), and the activities of lipid peroxide (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in PVECs were determined by flow cytometry and colorimetric assays, respectively. The levels of human PVEC-derived tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the supernatants of the co-culture system, and the activity of nuclear transcription factor-κB and NF-E2-related factor 2 (Nrf2) in PVECs were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TNF-α, IL-1β and IL-6 in PVECs was detected by quantitative real-time polymerase chain reaction (qRT-PCR), HO-1 expression and enzymatic activity in PVECs and the influence of zinc protoporphyrin (ZnPP) or HO-1 small interfering RNA on the above inflammatory and oxidative stress markers were evaluated. In addition, the expression of rat MSC-derived hepatocyte growth factor (HGF) and IL-10 was determined by ELISA and qRT-PCR. Results: MSCs showed no significant changes in phenotype or multilineage differentiation after transduction. LPS strongly increased the production of inflammatory and oxidative stress indicators, as well as decreased the levels of antioxidant components and the activity of Nrf2 in PVECs. MSC co-cultivation ameliorated these detrimental effects in PVECs and MSCs-HO-1 further improved the damage to PVECs induced by LPS when compared with MSCs alone. The beneficial effects of MSCs-HO-1 were dependent on HO-1 overexpression and may be attributed to the enhanced paracrine production of HGF and IL-10. Conclusion: MSCs-HO-1 have an enhanced ability to improve LPS-induced inflammatory and oxidative damage in PVECs, and the mechanism may be partially associated with the enhanced paracrine function of the stem cells. These data encourage further testing of the beneficial effects of MSCs-HO-1 in ALI animal models.

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Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?

Cited by 959 publications

References 156 publications

Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells

Qualitative Aspects of Bone Marrow Adiposity in Osteoporosis

Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells

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