A comparison between neurally induced bone marrow derived mesenchymal stem cells and olfactory ensheathing glial cells to repair spinal cord injuries in rat

Cell therapy has proven to be a highly promising method in clinical applications, raising so much hope for the treatment of injured tissues with low, if any, self regeneration potential such as central and peripheral nervous system. Neurally induced bone marrow derived mesenchymal stem cells (NIMSCs) as well as olfactory ensheathing cells (OECs) were transplanted in a rat model of sub-acute spinal cord injury and the behavioral and histological analyses were conducted. A balloon-compression technique was used to produce an injury at T8-T9 level of spinal cord. After a week post injury, rats were injected with either NIMSCs or OECs at the center of developing lesion cavity, 3 mm cranial and 3 mm caudal to the cavity. Weekly behavioral assessment using BBB score was done over five-week period post transplantation and finally histological assessment was performed to locate labeled cells in the tissue in order to evaluate the reduction of cavity formation and axonal regeneration. Evaluation of locomotor performance showed significant behavioral improvement in NIMSC group over OEC and control groups. The histological analyses revealed the presence of transplanted cells in the spinal cord parenchyma. Volume of injured area that was occupied with syrinx cavity in NIMSC group was significantly less than control group. In addition, meanwhile neurofilament-positive axons significantly showed higher expression in rats receiving NIMSC compared to the other two groups. In conclusion NIMSC caused both behavioral and histological improvement that potentially makes them a promising candidate for cell therapy approaches of spinal cord injuries.     

Subfractionation of cell populations by partitioning in dextran-poly (ethylene glycol) aqueous phases

Partitioning of cells in dextran-poly(ethylene glycol) aqueous two-phase systems depends on the interaction between the surface properties of the cells and the physical properties of the phases. The latter can be manipulated to a considerable extent by selection of polymer concentrations and ionic composition and concentration. If salts (e.g., phopshate) are used that have an unequal affinity for the two phases, an electrostatic potential difference between the phases results and, at appropriately high polymer concentrations, the partition coefficient of cells is determined predominantly by membrane charge-associated properties. By “balancing” the magnitude of the electrostatic potential difference against that of the interfacial tension (primarily a function of polymer, but also phosphate, concentrations) one can obtain phase systems that give usable partition coefficients for most cell populations (1). In work under way in our laboratory on the effects of different chemical and enzymatic modifications on the relative surface properties of rat red blood cells of different ages, we have now found that certain phase compositions did not resolve such treated cell subpopulations while other phase compositions did. Thus not all charged phase systems in which cell populations as a whole have usable partition coefficients are equally capable of detecting or subfractionating cell subpopulations. It is therefore essential, before drawing conclusions on the nonseqarability of cell subpopulations, to test cell separability in charged phase systems of different compositions if the system initially chosen does not afford a subfractionation.     

Meninigiomas of the Craniocervical Junction – A Distinctive Subgroup of Meningiomas

ObjectiveMeningioma of the cranio-cervical junction is a rare diagnosis and demand a thorough surgical planning as radical excision of these tumors is difficult. In this context recurrence is most likely due to regrowth of residual tumor. The aim of this study was to evaluate the clinical course of patients operated for craniocervical meningioma (CCM) and to investigate the histological features of these tumors and their impact on recurrence rate.MethodsAll patients who were operated for CCM at our institution between 2003 and 2012 were identified. Presenting symptoms, MRI findings, surgical approaches and recurrence rate were reviewed retrospectively using medical charts. Histological features of the included tumors were studied focusing on subtypes and MIB-1 immunoreactivity and compared with MIB-1 immunoreactivity in an age and gender-matched control group of patients with supratentorial meningioma.Results18 patients with CCM with a mean age of 56.2 years and median follow-up of 60 months were included in the study. Sensory or motor deficit was the most frequent presenting symptom followed by neck pain and lower cranial nerve palsy. Simpson grade II resection was achieved in 16 patients and Simpson grade III resection in two patients. Mortality, morbidity and recurrence rates were 16.7%, 5.5% and 5.5%, respectively. According to the WHO-grading all were found to be grade I meningiomas. Histological subtypes included meningotheliomatous (10), transitional (2), fibrillar (2), angiomatous (3) and secretory (1) meningioma. The mean MIB-1 labeling index in the study group was significantly higher than in the control group, (7.2% and 3.6%, respectively), p < 0.05. There was no correlation between MIB-1 levels and tumor recurrence.ConclusionsCCM seems to have a benign character. Despite a significantly higher MIB-1 index, a high rate of recurrence was not observed. Therefore, approaches with high morbidity are not justified. Nevertheless, in view of the challenging approaches with limited access to the lesion, CCM should be considered a distinctive clinical subgroup.     

Differential effect of neuraminidase-treatment on the surface charge-associated properties of rat reticulocytes and erythrocytes. Studies by partitioning in two-polymer aqueous phases

Rat reticulocytes undergo charge-associated surface changes, detectable by cell partitioning in charged dextran-poly(ethylene glycol) aqueous phase systems, as they become mature erythrocytes. Young reticulocytes have a lower partition coefficient, i.e., quantity of cells in the top phase as a percentage of total cells added, than do mature erythrocytes. Sialic acid is the main charge-bearing group on red blood cells and, in the case of the rat, most of the sialic acid can be removed by treatment of the cells with neuraminidase (Vibrio cholerae). By combining isotopic 59Fe-labeling of reticulocytes with countercurrent distribution of the entire red blood cell population in charged dextran-poly(ethylene glycol) aqueous phases we have now studied the relative effect of neuraminidase-treatment on rat reticulocytes and mature erythrocytes. It was found that neuraminidase-treatment (a) does not eliminate surface differences, detectable by partitioning, between rat reticulocytes and erythrocytes and (b) reduces the partition coefficient of mature erythrocytes to a greater extent than the partition coefficient of reticulocytes indicating a differential effect of this enzyme on the two cell populations.     

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.     

Local climatic adaptation in a widespread microorganism

Exploring the ability of organisms to locally adapt is critical for determining the outcome of rapid climate changes, yet few studies have addressed this question in microorganisms. We investigated the role of a heterogeneous climate on adaptation of North American populations of the wild yeast Saccharomyces paradoxus. We found abundant among-strain variation for fitness components across a range of temperatures, but this variation was only partially explained by climatic variation in the distribution area. Most of fitness variation was explained by the divergence of genetically distinct groups, distributed along a north–south cline, suggesting that these groups have adapted to distinct climatic conditions. Within-group fitness components were correlated with climatic conditions, illustrating that even ubiquitous microorganisms locally adapt and harbour standing genetic variation for climate-related traits. Our results suggest that global climatic changes could lead to adaptation to new conditions within groups, or changes in their geographical distributions.     

Tumor cell-derived exosomes: A message in a bottle

Exosomes constitute the newest mode of intercellular communication, transmitting information between cells. This exchange of molecular information is facilitated by their unique composition which is enriched with enzymes, structural proteins, adhesion molecules, lipid rafts and RNAs. Following the discovery that cancer cells secrete excessive amounts of exosomes compared to normal cells, it became evident that i) these vesicles can be used as diagnostic markers; ii) their active secretion has functional implications, albeit unknown whether they are tumor promoting or suppressing. Notably, the interplay via the exchange of exosomes between cancer cells and between cancer cells and the tumor stroma may promote the transfer of oncogenes (e.g. β-catenin, CEA, HER2, Melan-A/Mart-1 and LMP-1) and onco-microRNAs (e.g. let7, miR1, miR15, miR16 and miR375) from one cell to another, leading to the reprogramming of the recipient cells. The molecular composition and functional role of tumor cell-derived exosomes in tumorigenesis, metastasis and response to therapy are slowly decrypted and the latest findings as well as potential therapeutic strategies are discussed in this review.