BackgroundHuman adipose-derived mesenchymal stem cells (ADMSCs) may be ideal source of cells for intervertebral disc (IVD) regeneration, but the harsh chemical microenvironment of IVD may significantly influence the biological and metabolic vitality of ADMSCs and impair their repair potential. This study aimed to investigate the viability, proliferation and the expression of main matrix proteins of ADMSCs in the chemical microenvironment of IVD under normal and degeneration conditions.MethodsADMSCs were harvested from young (aged 8-12 years, n = 6) and mature (aged 33-42 years, n = 6) male donors and cultured under standard condition and IVD-like conditions (low glucose, acidity, high osmolarity, and combined conditions) for 2 weeks. Cell viability was measured by annexin V-FITC and PI staining and cell proliferation was measured by MTT assay. The expression of aggrecan and collagen-I was detected by real-time quantitative polymerase chain reaction and Western blot analysis.ResultsIVD-like glucose condition slightly inhibited cell viability, but increased the expression of aggrecan. In contrast, IVD-like osmolarity, acidity and the combined conditions inhibited cell viability and proliferation and the expression of aggrecan and collagen-I. ADMSCs from young and mature donors exhibited similar responses to the chemical microenvironments of IVD.ConclusionIVD-like low glucose is a positive factor but IVD-like high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of ADMSCs. These findings may promote the translational research of ADMSCs in IVD regeneration for the treatment of low back pain.

The microenvironment of the intervertebral disc (IVD) is characterized by matrix acidity, hypoxia, hyperosmolarity and limited nutrition, which are major obstacles to stem cell-based regeneration. Our recent work showed that nucleus pulposus mesenchymal stem cells (NPMSCs) had advantages over traditional sources of cell therapy under IVD-like hypoxic and hyperosmotic conditions. Here, we examined the viability, proliferation and matrix metabolism of NPMSCs compared with adipose tissue-derived mesenchymal stem cells (ADMSCs) under IVD-like acidic conditions in vitro. ADMSCs and NPMSCs from Sprague-Dawley rats were cultured at four different pH levels representing the standard condition (pH 7.4) and the normal, mildly degenerated and severely degenerated IVD (pH 7.1, 6.8 and 6.5, respectively). Cell viability was examined by annexin-V-fluorescein isothiocyanate/propidium iodide staining. Cell proliferation was measured using a cell counting kit cell proliferation assay. The expression of aggrecan, collagen-I, collagen-II, matrix metalloproteinase-2 (MMP-2), a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) and the tissue inhibitor of metalloproteinase-3 (TIMP-3) was measured at mRNA and protein levels by RT-PCR and Western blotting. In both cell types, acidic pH inhibited cell viability and proliferation, downregulated the expression of aggrecan, collagen-I, collagen-II and TIMP-3, and upregulated the expression of MMP-2 and ADAMTS4. Compared with ADMSCs, NPMSCs were significantly less inhibited in viability and proliferation; they expressed significantly higher levels of aggrecan and collagen-II, and lower levels of MMP-2 and ADAMTS4. Thus, an acidic environment is a major obstacle for IVD regeneration by ADMSCs or NPMSCs. NPMSCs appeared less sensitive to inhibition by acidic pH and might be promising candidates for cell-based IVD regeneration.

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Prostate cancer (PCa) is the leading cause of cancer-related death among men worldwide. Knowledge of the prognostic factors of PCa and the bone metastasis pattern of patients would be helpful for patients and doctors. The data of 177,255 patients with prostate cancer diagnosed between 2010 and 2013 with at least five years of follow-up were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determine the predictive value of patients’ characteristics for survival after adjusting for other variates. Multivariate logistic regression analysis was used to evaluate the odds ratio of bone metastasis in PCa patients. The predictive value of age, race, marital status, and tumor characteristics were compared. The survival of patients with different socioeconomic statuses and bone metastasis statuses was compared by Kaplan–Meier analysis. A total of 1,335 patients with prostate cancer diagnosed between 2009 and 2015 were enrolled from the Second Affiliated Hospital of Zhejiang University School of Medicine. The survival of patients with different prostate-specific antigen (PSA) levels, Gleason scores, marital statuses and bone metastasis statuses was compared by Kaplan-Meier analysis. In SEER database, 96.74% of patients were 50 years of age or older. Multivariate Cox analysis revealed that for PCa patients, age at presentation, older age, single marital status, lower socioeconomic status, higher PSA level, T1 and N0 stage, and bone metastasis were independent risk factors for increased mortality. Multivariate logistic regression analysis revealed that patients who were married, were living in urban areas, had lower PSA levels, underwent surgery, and radiation had lower OR factors for bone metastasis. Asian or Pacific Islander, better socioeconomic status, lived in urban areas, married marital status, lower PSA levels and lower Gleason scores were better prognostic factors in PCa. Additionally, patients with single or divorced marital status, who were living in rural places had higher PSA levels, and T1 and N0 stages have a high OR for bone metastasis.