Soft tissue regeneration in animal models using grafts from adipose mesenchymal stem cells and peripheral blood fibrin gel.

OBJECTIVE: Our study aimed to evaluate the effect of soft tissue regeneration in nude mice using grafts made from the combination of adipocytes from fat tissue mesenchymal stem cells and fibrin gel from peripheral blood. MATERIALS AND METHODS: Mesenchymal stem cells were isolated from adipose tissue and identified according to ISCT criteria. The scaffold used was fibrin obtained from peripheral blood. The grafts in this study were generated by transferring mesenchymal stem cells onto a fibrin scaffold. Two types of grafts, the research sample (fibrin scaffold containing adipocytes differentiated from mesenchymal stem cells) and the control sample (fibrin scaffold only), were grafted under the dorsal skin of the same mouse. After each research period, samples were collected and evaluated by histological methods to observe the existence and growth of cells inside the grafts. RESULTS: The results showed that the study group's graft integrated better within the tissue when compared with the control group. In addition, the grafts in the study group showed the presence of cells with characteristic morphology of adipocytes one week after transplantation. In contrast, control samples showed dimorphous shapes and features mainly composed of non-homogenous fragments. CONCLUSIONS: These initial conclusions might be considered a first step in generating safe bio-compatible engineered grafts specifically usable in post-traumatic tissue regeneration procedures.

Diagnostic performance of MRI perfusion and spectroscopy for brainstem glioma grading.

OBJECTIVE: This study investigated the roles of dynamic susceptibility contrast (DSC) perfusion and multivoxel magnetic resonance spectroscopy (MRS) in grading brainstem glioma (BSG). PATIENTS AND METHODS: Our retrospective study comprised 12 patients, including 6 with pathology verified low-grade BSGs and 6 with high-grade BSGs. We examined differences in age, relative cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and the metabolite ratios of choline (Cho)/N-acetyl aspartate (NAA) and Cho/creatine (Cr) between these two groups using the Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve analysis was used to establish cutoff values and assess their usefulness in grading BSG. RESULTS: The Cho/NAA metabolite ratio had the strongest preoperative predictive performance for identifying the correct histological grade among BSGs, with an area under the ROC curve (AUC) value of 0.944 (cutoff: 3.88, sensitivity [Se]: 83.3%; specificity [Sp]: 100%), followed by the Cho/Cr ratio (cutoff: 3.08; AUC: 0.917; Se: 83.3%; Sp: 100%), rCBF (cutoff: 3.56, AUC: 0.917; Se: 83.3%; Sp: 100%), rCBV (cutoff: 3.16, AUC: 0.889; Se: 100%; Sp: 66.7%), and age (cutoff: 9.5 years, AUC: 0.889; Se: 100%; Sp: 83.3%). CONCLUSIONS: rCBF and rCBV values comparing solid tumors with the normal brain parenchyma and the metabolite ratios for Cho/NAA and Cho/Cre may serve as useful indices for establishing BSG grading and provide important information when determining treatment planning and prognosis in patients with BSG.

Diagnostic performance of quantitative signal intensity measurements on magnetic resonance imaging for distinguishing cerebellopontine angle meningioma from acoustic schwannoma.

OBJECTIVE: Our study investigated magnetic resonance imaging measurements for differentiating cerebellopontine angle (CPA) meningioma from vestibular schwannoma (VS). PATIENTS AND METHODS: This retrospective study compared 36 meningioma and 36 VS patients. The tumor volume (Vtumor) and peritumor edema index (EI) relationship was analyzed. T2-weighted three-dimensional gradient-echo image signal intensity (T23D) and apparent diffusion coefficient (ADC) differentiation cutoff values were defined. Mann-Whitney U test, independent-samples t-test, receiver operating characteristic curve, and Spearman's correlation analyses were applied. RESULTS: Meningioma had higher Vtumor (p=0.009) and EI (p=0.031) values than VS. Meningioma had significantly (p<0.001) lower values than VS for mean ADC (ADCmean: 0.841±0.083×10-3 vs.1.173±0.190×10-3 mm2/s), minimum ADC (ADCmin: 0.716±0.078×10-3 vs.1.045±0.178×10-3 mm2/s), tumor:white matter ADC ratio (rADC: 1.198±0.19 vs. 1.59±0.30), mean T23D (T23Dmean: 142.91±19.9 vs. 218.72±84.73), and tumor:adipose T23D ratio (rT23d: 0.19±0.06 vs. 0.30±0.28) Cutoff, sensitivity (Se), and specificity (Sp) values were ADCmin, 0.856×10-3 mm2/s (Se: 96.6%, Sp: 100%); ADCmean, 0.963×10-3 mm2/s (Se: 96.6%, Sp: 95.5%); rADC, 1.3189 (Se: 93.1%, Sp: 81.8%), T23Dmean (Se: 96.6%, Sp: 100%); rT23D, 0.1951 (Se: 89.7%, Sp: 100%), Vtumor, 14828.65 mm3 (Se: 75.0%, Sp: 66.7%), and EI, 1.1025 (Se: 47.2%, Sp: 100%). CONCLUSIONS: ADCmin, ADCmean, rADC, T23Dmean, rT23D, Vtumor, and EI, effectively discriminated meningioma from VS.

A dynamic model for induced reactivation of latent virus.

We develop a deterministic mathematical model to describe reactivation of latent virus by chemical inducers. This model is applied to the reactivation of latent KSHV in BCBL-1 cell cultures with butyrate as the inducing agent. Parameters for the model are first estimated from known properties of the exponentially growing, uninduced cell cultures. Additional parameters that are necessary to describe induction are determined from fits to experimental data from the literature. Our initial model provides good agreement with two independent sets of experimental data, but also points to the need for a new class of experiments which are required for further understanding of the underlying mechanisms.

Ca2+-calmodulin regulates the induction and expression of macrophage cytotoxicity.

Ca2+-activated calmodulin (CAM) is known to regulate cellular responses of diverse cell types to external stimuli. To examine the effects of Ca2+ influx and CAM on macrophage (MP) cytotoxicity, we used 51Cr-labeled cells as targets and in vivo or in vitro activated MPs from C57 BL/6 or BALB/c mice as effectors in a 16-h cytotoxicity assay. MPs activated in vivo by administration of vaccinia virus or in vitro with lymphokine (LK) were cytotoxic for a variety of tumor cell lines, including SV3T3, but not for normal 3T3 cells. Addition of verapamil (0.1 mM), a Ca2+ channel blocker, to MPs activated in vivo by vaccinia virus markedly reduced their cytotoxicity for SV3T3 cells. This correlated with an inhibition of Ca2+ uptake by MPs, as measured by 45Ca influx. Chlorpromazine (20 microM), trifluoperazine (20 microM), and W13 (75 microM), inhibitors of CAM activity, also suppressed MP cytotoxicity for SV3T3 cells when added to the assay, suggesting that Ca2+-activated CAM is an integral component in expression of MP cytotoxicity. To further explore the mechanism of MP cytotoxicity, supernatants from activated MPs treated with various pharmacological agents were examined for cytotoxicity. Vaccinia-activated MPs released a soluble factor(s) that was cytotoxic for SV3T3 cells. Resident MPs cultured under the same condition produced no significant cytotoxic activity. As observed with direct MP cytotoxicity, addition of a Ca2+ channel blocker or CAM inhibitors to cultured activated MPs markedly reduced the cytotoxic activity of the supernatants, suggesting an active secretory process. The requirement for Ca2+ and CAM in the expression of MP cytotoxicity was confirmed in an in vitro MP activation system. Resident cultured MPs activated by an LK preparation were reduced in their tumoricidal capability when verapamil or CAM inhibitors were added to the cytotoxicity assay. This correlated with a reduction in lytic activity of the MP culture supernatants. Further, addition of verapamil or CAM inhibitors to resident MP cultures markedly reduced the induction of tumoricidal MPs by LK, suggesting that Ca2+ and CAM are necessary for both the induction and the expression of MP cytotoxicity. Suppression of cytotoxicity of in vitro activated MP cell line B6MP102 with verapamil and CAM inhibitors confirmed that the MP was the cytotoxic cell being modulated by Ca2+-activated CAM.(ABSTRACT TRUNCATED AT 400 WORDS)