Cellular Heterogeneity of Mesenchymal Stem/Stromal Cells in the Bone Marrow.

Mesenchymal stem/stromal cells (MSCs) are present in various body tissues and help in maintaining homeostasis. The stemness of MSCs has been evaluated in vitro. In addition, analyses of cell surface antigens and gene expression patterns have shown that MSCs comprise a heterogeneous population, and the diverse and complex nature of MSCs makes it difficult to identify the specific roles in diseases. There is a lack of understanding regarding the classification of MSC properties. In this review, we explore the characteristics of heterogeneous MSC populations based on their markers and gene expression profiles. We integrated the contents of previously reported single-cell analysis data to better understand the properties of mesenchymal cell populations. In addition, the cell populations involved in the development of myeloproliferative neoplasms (MPNs) are outlined. Owing to the diversity of terms used to describe MSCs, we used the text mining technology to extract topics from MSC research articles. Recent advances in technology could improve our understanding of the diversity of MSCs and help us evaluate cell populations

Prospective isolation of murine and human bone marrow mesenchymal stem cells based on surface markers,”

Mesenchymal stem cells (MSCs) are currently defined as multipotent stromal cells that undergo sustained in vitro growth and can give rise to cells of multiple mesenchymal lineages, such as adipocytes, chondrocytes, and osteoblasts. The regenerative and immunosuppressive properties of MSCs have led to numerous clinical trials exploring their utility for the treatment of a variety of diseases (e.g., acute graft-versus-host disease, Crohn's disease, multiple sclerosis, osteoarthritis, and cardiovascular diseases including heart failure and myocardial infarction). On the other hand, conventionally cultured MSCs reflect heterogeneous populations that often contain contaminating cells due to the significant variability in isolation methods and the lack of specific MSC markers. This review article focuses on recent developments in the MSC research field, with a special emphasis on the identification of novel surface markers for the in vivo localization and prospective isolation of murine and human MSCs. Furthermore, we discuss the physiological importance of MSC subtypes in vivo with specific reference to data supporting their contribution to HSC niche homeostasis. The isolation of MSCs using selective markers (combination of PDGFR and Sca-1) is crucial to address the many unanswered questions pertaining to these cells and has the potential to enhance their therapeutic potential enormously

LNGFR+THY-1+VCAM-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells

Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the combination of three cell-surface markers (LNGFR, THY-1, and VCAM-1) allows for the selection of highly enriched clonogenic cells (one out of three isolated cells). Clonal characterization of LNGFR(+)THY-1(+) cells demonstrated cellular heterogeneity among the clones. Rapidly expanding clones (RECs) exhibited robust multilineage differentiation and self-renewal potency, whereas the other clones tended to acquire cellular senescence via P16INK4a and exhibited frequent genomic errors. Furthermore, RECs exhibited unique expression of VCAM-1 and higher cellular motility compared with the other clones. The combination marker LNGFR(+)THY-1(+)VCAM-1(hi+) (LTV) can be used selectively to isolate the most potent and genetically stable MSCs

Oxidation of DJ-1 Induced by 6-Hydroxydopamine Decreasing Intracellular Glutathione

DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported to undergo preferential oxidation of the cysteine residue at position 106 (Cys-106) under oxidative stress; however, details of the molecular mechanisms are not well known. In the present study, mechanisms of DJ-1 oxidation induced by 6-hydroxydopamine (6-OHDA) were investigated by using SH-SY5Y cells. The treatment of these cells with 6-OHDA caused an obvious acidic spot sift of DJ-1 due to its oxidation. However, when catalase, which is an hydrogen peroxide (H2O2)-removing enzyme, was added during the treatment, it failed to prevent the oxidation induced by 6-OHDA, suggesting that electrophilic p-quinone formed from 6-OHDA, but not H2O2, was responsible for the DJ-1 oxidation. Benzoquinone, another electrophilic p-quinone, also induced DJ-1 oxidation. The intracellular glutathione (GSH) levels were significantly decreased by 6-OHDA, irrespective of the presence or absence of catalase. The inhibition of GSH synthesis by buthionine sulfoximine resulted in a decrease in GSH levels and enhancement of DJ-1 oxidation. The pretreatment of cells with N-acetyl-cysteine prevented the loss of intracellular GSH and subsequently DJ-1 oxidation induced by 6-OHDA. Collectively, these results suggest that electrophilic p-quinone formed from 6-OHDA induces DJ-1 oxidation by decreasing intracellular GSH

Does sarcopenia affect postoperative short- and long-term outcomes in patients with lung cancer?-a systematic review and meta-analysis.

Background:Lung cancer patients frequently suffer from sarcopenia, and reports on the association of resectable lung cancer and their postoperative outcomes are increasing. Information on whether sarcopenia has any impact on short- and long-term postoperative outcomes in patients surgically treated for non-small cell lung cancer remains insufficient. Furthermore, reports vary regarding the pathological stage, surgical procedure, diagnostic tool of sarcopenia, cut-off value, prognosis, and postoperative complications. We believe that sarcopenia assessment should be included as one of the factors which affect the surgical outcomes of lung cancer. Thus, we conducted a review and meta-analysis to ascertain the association between sarcopenia and postoperative outcomes.Methods:We performed a systematic literature search in PubMed/MEDLINE. Studies included cases defined sarcopenia, received lung cancer surgery, assessed postoperative complications, and prognosis. The pooled odds ratios for survival and postoperative complications, with 95% confidence intervals, were generated using Review manager 5.3.Results:A total of ten retrospective studies were eligible for this meta-analysis, including a total of 2,643 non-small cell lung cancer patients. All reviews used skeletal muscle mass as a diagnostic tool for sarcopenia. Sarcopenia was associated with worse survival outcomes and increased postoperative complications in patients with resected lung cancer.Conclusions:Sarcopenia is an independent risk factor for postoperative death and postoperative complications in patients who have undergone surgery. It is necessary to explore the mechanism of sarcopenia and optimal intervention, such as exercise, nutrition, or drug therapy

Sarcopenia increases the risk of post-operative recurrence in patients with non-small cell lung cancer.

Background:Sarcopenia is among the most prevalent and serious cancer-related symptom, and is strongly correlated with a poor prognosis. Moreover, it reportedly predicts poor prognosis after surgery in patients with lung cancer. However, it is unclear whether sarcopenia directly affects post-operative recurrence. The purpose of this study was to evaluate whether sarcopenia can be a risk indicator for post-operative recurrence, and whether it suppresses anti-tumor immunity, in a cohort of patients with resected non-small cell lung cancer.Methods:This study retrospectively reviewed the data of 256 consecutive patients who underwent curative lobectomy and lymph node dissection for non-small cell lung cancer at our institution. The psoas muscle mass index was calculated as the total psoas muscle area at the third lumbar vertebral level/height2 (cm2/m2). Sarcopenia was defined by a psoas muscle mass index of under 5.03 cm2/m2 and 3.17 cm2/m2 in male and female patients, respectively. Post-operative prognosis and cumulative incidence of recurrence rates were calculated.Results:The 5-year overall survival and disease-free survival rates post-surgery were 59.5% and 38.6%, respectively, in patients with sarcopenia versus 81.1% and 72.1%, respectively, in patients without sarcopenia (p < 0.001). The 5-year cumulative incidence of recurrence rate in patients with sarcopenia was significantly higher than those without sarcopenia (49.9% versus 22.4%, respectively) in every pathological stage. Pathological stages II and III (hazard ratio, 3.36; p = 0.004), histological type (hazard ratio, 2.31; p = 0.025), and sarcopenia (hazard ratio, 2.52; p = 0.001) were independent risk factors for post-operative recurrence according to multivariate analysis.Conclusion:Sarcopenia is a risk indicator for post-operative recurrence in patients with non-small cell lung cancer

Locoregional recurrence via mucus-mediated extension following lung resection for mucinous tumors.

Background:Clinically, locoregional recurrences following mucinous tumor resection are often experienced. However, it remains unclear whether mucinous tumors directly affect local recurrence or not, and if so, the mechanism is not known. Therefore, we investigated whether mucinous tumors are associated with locoregional recurrence after pulmonary resection and whether mucus extension is a risk factor for locoregional recurrence.Methods:The data of 152 patients who underwent pulmonary resection for metastases were reviewed. When mucus was partially or wholly present in the tumor based on macro- or microscopic identification, we assigned the tumor as mucinous. In mucinous tumors, when mucus was identified within the air spaces in the normal lung parenchyma, beyond the edge of the tumor, we assigned the tumor as positive for "mucus extension."Results:The 5-year cumulative incidence of locoregional recurrence in patients with mucinous tumors was 48.1%, which was significantly higher than that observed in those with non-mucinous tumors (14.9%). Within the mucinous tumor, the presence of mucus extension beyond the tumor edge was an independent risk factor for locoregional recurrence after pulmonary resection (hazard ratio, 5.52; P = 0.019).Conclusions:During the resection of mucinous cancer, surgeons should maintain sufficient distance from the tumor edge to prevent locoregional recurrences

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Technical advantage of recombinant collagenase for isolation of muscle stem cells

Background: Muscle satellite cells are resident skeletal muscle stem cells responsible for muscle regeneration. Isolation of satellite cells is a critical process for clinical application such as drug screening and cell transplantation. Fluorescence-activated cell sorting (FACS) enables the direct isolation of satellite cells from muscle tissue. During the process used to isolate satellite cells from skeletal muscle, enzymatic digestion is the first step. Therefore, the evaluation and standardization of enzymes is important not only for reproducibility of cellular yield and viability, but also for traceability of material used in protocols. Methods: The comparison of muscle digestion was performed either by a mixture of recombinant collagenase G (ColG) and collagenase H (ColH) or by a conventional collagenase II. The degree of cell damage and surface antigen expression upon collagenase treatment were analyzed by FACS. To investigate whether satellite cells isolated using recombinant collagenase can regenerate injured muscle, satellite cells were cultured, transplanted into injured muscles, and analyzed by immunostaining. Results: We show that ColG and ColH were efficient to isolate satellite cells from mouse skeletal muscle tissue. Digestion with a combination of ColG and ColH enriched satellite cells with intact surface antigens such as α7 and β1 integrins. Furthermore, satellite cells isolated using ColG and ColH dramatically proliferated and remained undifferentiated in vitro. When transplanted, satellite cells isolated using ColG and ColH enhanced the therapeutic efficacy in vivo. Conclusions: Our results provide an efficient method of satellite cell preparation using recombinant collagenases with a high cell yield, viability of cells, and regeneration potency to fit the biological raw material criteria