Aging of the inceptive cellular population: the relationship between stem cells and aging

The average life expectancy worldwide has about doubled and the global population has increased six fold over the past century. With improving health care in the developed world there is a proportional augmentation in the treatment necessary for elderly patients occasioning the call for increased research in the area of aging and age-related diseases. The manifestation of this research has been focalized on the causative cellular processes and molecular mechanisms involved. Here we will discuss the efforts of this research in the area of stem cells, delving into the regulatory mechanisms and how their de-regulation could be attributed to aging and age-related diseases

Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells.

Self-renewal, proliferation and differentiation properties of stem cells are controlled by key transcription factors. However, their activity is modulated by chromatin remodeling factors that operate at the highest hierarchical level. Studies on these factors can be especially important to dissect molecular pathways governing the biology of stem cells. SWI/SNF complexes are adenosine triphosphate (ATP)-dependent chromatin remodeling enzymes that have been shown to be required for cell cycle control, apoptosis and cell differentiation in several biological systems. The aim of our research was to investigate the role of these complexes in the biology of mesenchymal stem cells (MSCs). To this end, in MSCs we caused a forced expression of the ATPase subunit of SWI/SNF (Brg1 – also known as Smarca4) by adenoviral transduction. Forced Brg1 expression induced a significant cell cycle arrest of MSCs in culture. This was associated with a huge increase in apoptosis that reached a peak 3 days after transduction. In addition, we observed signs of senescence in cells having ectopic Brg1 expression. At the molecular level these phenomena were associated with activation of Rb- and p53-related pathways. Inhibition of either p53 or Rb with E1A mutated proteins allowed us to hypothesize that both Rb and p53 are indispensable for Brg1-induced senescence, whereas only p53 seems to play a role in triggering programmed cell death. We also looked at the effects of forced Brg1 expression on canonical MSC differentiation in adipocytes, chondrocytes and osteocytes. Brg1 did not induce cell differentiation per se; however, this protein could contribute, at least in part, to the adipocyte differentiation process. In conclusion, our results suggest that whereas some ATP-dependent chromatin remodeling factors, such as ISWI complexes, promote stem cell self-renewal and conservation of an uncommitted state, others cause an escape from ‘stemness’ and induction of differentiation along with senescence and cell death phenomena

Long-Lasting Effects of Human Mesenchymal Stem Cell Systemic Administration on Pain-Like Behaviors, Cellular, and Biomolecular Modifications in Neuropathic Mice

Background: Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain. Methods: Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery. Results: hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice. Conclusion: As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine

Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS) as a Tool to Characterize Plastic Polymers in a Marine Environment

In the last 60 years, plastic has become a widely used material due to its versatility and wide range of applications. This characteristic, together with its persistence, makes plastic waste a growing environmental problem, particularly in the marine ecosystems. The production of plant-derived biodegradable plastic polymers is assuming increasing importance. Here, we report the results of a first preliminary characterization of carbon stable isotopes (δ13C) of different plastic polymers (petroleum- and plant-derived) and a first experimental study aimed to determine carbon isotopic shift due to polymer degradation in an aquatic environment. The results showed that the δ13C values determined in different packaging for food uses reflect the plant origin for “BIO” materials and the petroleum-derived source for plastic materials. Considering degradation, δ13C values of both bio bags and HDPE bags showed a gradual decrease toward less negative values when kept immersed in seawater, recording a δ13C variation (Δδ13C) of 1.15 and 1.78‰, respectively. With respect to other analytical methods, the characterization of the plastic polymer composition by isotope ratio mass spectrometry is advantageous due to low cost and rapidity of analysis, small amount of sample required, high sensitivity, and the possibility of analyzing colored samples

Andrea Chenier

De cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents.Direcció: Laszlo HalaszEmpresa: Juan A. Pamia

Andrea Chenier

De cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents.Direcció: José Sabater ; Direcció escènica: Juan VillaviciosaEmpresa: Juan Mestres Calve

Andrea Chénier

Director: G. FalconiDe cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents

Survival and Prognostic Factors in Patients with Hepatocellular Carcinoma Treated by Percutaneous Ethanol Injection: A 10-Year Experience

The treatment of early and intermediate stage hepatocellular carcinoma (HCC) is still debated. Surgical treatments are considered to be the only curative procedures available, and only for a minority of patients. Percutaneous ethanol injection (PEI) is an established technique for the ablation of HCC nodules, and shows survival rates similar to those of resection. The efficacy of PEI in patients with biopsy-proven viral cirrhosis and small to intermediate inoperable HCC was evaluated. One hundred twenty-seven patients (85 men, 42 women, mean age 63 years, range 51 to 92 years, 115 hepatitis C virus-positive, 12 hepatitis B virus-positive) were enrolled between January 1993 and December 2002. They all underwent a standard PEI procedure and were prospectively followed-up. Overall median survival rate was 28 months (range six to 112 months). The following parameters were associated with a significantly longer survival: nodule diameter smaller than 30 mm (P=0.0480), the presence of a perinodular boundary (P=0.0008), serum alpha-fetoprotein less than 20 ng/mL (P=0.0104), a Child-Pugh A class score (PÃ0.0001) or a Cancer of the Liver Italian Program score of 0 (PÃ0.0001) and the presence or absence of small esophageal varices (P=0.013). The 19 patients with all these favourable characteristics showed an overall median survival of 61 months. An alpha-fetoprotein below 20 ng/mL was associated with significantly longer disease-free survival (P=0.0009). The Child-Pugh and Cancer of the Liver Italian Program scores were effective in predicting prognosis of these patients. In conclusion, PEI still represents a safe and economically sound treatment for HCC

Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma