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Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica.

ABSTRACT: Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow?derived mesenchymal stem cells (BM?MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM?MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM?MSCs from patients with NMO with that of age? and sex?matched healthy subjects. It was revealed that there were no significant differences in terms of cell morphology or differentiation capacities in the BM?MSCs from the patients with NMO. However, in comparison with healthy controls, BM?MSCs derived from the Patients with NMO exhibited a decreased proliferation rate, in addition to a decreased expression of several cell cycle?promoting and proliferation?associated genes. Furthermore, the cell death rate increased in BM?MSCs from patients under normal culture conditions and an assessment of the gene expression profile further confirmed that the BM?MSCs from patients with NMO were more vulnerable to senescence. Platelet?derived growth factor (PDGF), as a major mitotic stimulatory factor for MSCs and a potent therapeutic cytokine in demyelinating disease, was able to overcome the decreased proliferation rate and increased senescence defects in BM?MSCs from the patients with NMO. Taken together, the results from the present study have enabled the proposition of the possibility of combining the application of autologous BM?MSCs and PDGF for refractory and severe patients with NMO in order to elicit improved therapeutic effects, or, at the least, to include PDGF as a necessary and standard growth factor in the current in vitro formula for the culture of NMO patient?derived BM?MSCs.

SUBMITTER: Yang C

PROVIDER: S-EPMC6365084 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica.

Yang Chunsheng C Yang Yang Y Ma Li L Zhang Guang-Xian GX Shi Fu-Dong FD Yan Yaping Y Chang Guoqiang G

International journal of molecular medicine 20190109 3

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM‑MSCs from patients with NMO, which may influence any therapeutic effects. The present study ai ...[more]

PMID: 30628649

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Project description:Marrow adipose tissue (MAT) has been shown to be vital for regulating metabolism and maintaining skeletal homeostasis in the bone marrow (BM) niche. As a reflection of BM remodeling, MAT is highly responsive to nutrient fluctuations, hormonal changes, and metabolic disturbances such as obesity and diabetes mellitus. Expansion of MAT has also been strongly associated with bone loss in mice and humans. However, the regulation of BM plasticity remains poorly understood, as does the mechanism that links changes in marrow adiposity with bone remodeling. We studied deletion of Adipsin, and its downstream effector, C3, in C57BL/6 mice as well as the bone-protected PPARγ constitutive deacetylation 2KR mice to assess BM plasticity. The mice were challenged with thiazolidinedione treatment, calorie restriction, or aging to induce bone loss and MAT expansion. Analysis of bone mineral density and marrow adiposity was performed using a μCT scanner and by RNA analysis to assess adipocyte and osteoblast markers. For in vitro studies, primary bone marrow stromal cells were isolated and subjected to osteoblastogenic or adipogenic differentiation or chemical treatment followed by morphological and molecular analyses. Clinical data was obtained from samples of a previous clinical trial of fasting and high-calorie diet in healthy human volunteers. We show that Adipsin is the most upregulated adipokine during MAT expansion in mice and humans in a PPARγ acetylation-dependent manner. Genetic ablation of Adipsin in mice specifically inhibited MAT expansion but not peripheral adipose depots, and improved bone mass during calorie restriction, thiazolidinedione treatment, and aging. These effects were mediated through its downstream effector, complement component C3, to prime common progenitor cells toward adipogenesis rather than osteoblastogenesis through inhibiting Wnt/β-catenin signaling. Adipsin promotes new adipocyte formation and affects skeletal remodeling in the BM niche. Our study reveals a novel mechanism whereby the BM sustains its own plasticity through paracrine and endocrine actions of a unique adipokine. This work was supported by the National Institutes of Health T32DK007328 (NA), F31DK124926 (NA), R01DK121140 (JCL), R01AR068970 (BZ), R01AR071463 (BZ), R01DK112943 (LQ), R24DK092759 (CJR), and P01HL087123 (LQ).

Dataset Information

Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica.

Publications

Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica.

Similar Datasets

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