March 10th, 2010 / No Comments » / by Caocci G, Baccoli R, Vacca A, Mastronuzzi A, Bertaina A, Piras E, Littera R, Locatelli F, Carcassi C, La Nasa G
Comparison between an artificial neural network and logistic regression in predicting acute graft-versus-host disease following unrelated donor hematopoietic stem cell transplantation in thalassemia patients.
Exp Hematol. 2010 Mar 3;
Authors: Caocci G, Baccoli R, Vacca A, Mastronuzzi A, Bertaina A, Piras E, Littera R, Locatelli F, Carcassi C, La Nasa G
OBJECTIVE: There is growing interest in the development of prognostic models for predicting the occurrence of acute graft-versus-host disease (aGVHD) following unrelated donor hematopoietic stem cell transplantation (UD-HSCT). A high number of variables have been shown to play a role in aGVHD, but the search for a predictive algorithm is still ongoing. Artificial neural networks (ANNs) represent an attractive alternative to multivariate analysis for clinical prognosis. So far, no reports have investigated the ability of ANNs in predicting HSCT outcome. METHODS: We compared the prognostic performance of ANNs with that of logistic regression (LR) in 78 beta-thalassemia major patients given UD-HSCT. Twenty-four independent variables were analyzed for their potential impact on outcome. RESULTS: Twenty-six patients (33.3%) developed grade II-IV aGVHD. In multivariate analysis, homozygosity for donor KIR haplotype A (p=0.03), donor age (p=0.05) and donor homozygosity for the deletion of the HLA-G 14-bp polymorphism (p=0.05) were independently significantly correlated to aGVHD. The mean sensitivity of LR and ANNs (capability of predicting aGVHD in patients who developed aGVHD) in test data sets was 21.7% and 83.3% respectively (p<0.001); the mean specificity (capability of predicting absence of aGVHD in patients who did not develop aGVHD) was 80.5% and 90.1% respectively (p=NS). CONCLUSION: Although ANNs are unable to calculate the weight of single variables on outcome, they were found to have a better performance than LR. A combination of these two methods could be more efficient in predicting outcomes and help tailor GVHD prophylaxis regimens according to the predicted risk of each patient. Whether ANN technology will provide better predictive performance when applied to other data sets remains to be confirmed.
PMID: 20206661 [PubMed - as supplied by publisher]
Posted in: Exp Hematol
March 10th, 2010 / No Comments » / by Choi YY, Chung BG, Lee DH, Khademhosseini A, Kim JH, Lee SH
Controlled-size embryoid body formation in concave microwell arrays.
Biomaterials. 2010 Mar 4;
Authors: Choi YY, Chung BG, Lee DH, Khademhosseini A, Kim JH, Lee SH
Embryonic stem (ES) cells hold great potential as a renewable cell source for regenerative medicine and cell-based therapy. Despite the potential of ES cells, conventional stem cell culture methods do not enable the control of the microenvironment. A number of microscale engineering approaches have been recently developed to control the extracellular microenvironment and to direct embryonic stem cell fate. Here, we used engineered concave microwell arrays to regulate the size and shape of embryoid bodies (EBs)-cell aggregate intermediates derived from ES cells. Murine ES cells were aggregated within concave microwells, and their aggregate sizes were controlled by varying the microwell widths (200, 500, and 1000 mum). Differentiation of murine ES cells into three germ layers was assessed by analyzing gene expression. We found that ES cell-derived cardiogenesis and neurogenesis were strongly regulated by the EB size, showing that larger concave microwell arrays induced more neuronal and cardiomyocyte differentiation than did smaller microwell arrays. Therefore, this engineered concave microwell array could be a potentially useful tool for controlling ES cell behavior.
PMID: 20206991 [PubMed - as supplied by publisher]
Posted in: Biomaterials
March 10th, 2010 / No Comments » / by Chen K, Wang D, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Zhu D, Bayard F, Han ZC
Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE(2)-dependent mechanism.
Clin Immunol. 2010 Mar 4;
Authors: Chen K, Wang D, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Zhu D, Bayard F, Han ZC
Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) constitute an attractive alternative to bone-marrow-derived MSCs for potential clinical applications because of easy preparation and lower risk of viral contamination. In this study, both proliferation of human peripheral blood mononuclear cells (hPBMCs) and their IFN-gamma production in response to mitogenic or allogeneic stimulus were effectively inhibited by hUC-MSCs. Co-culture experiments in transwell systems indicated that the suppression was largely mediated by soluble factor(s). Blocking experiments identified prostaglandin E(2) (PGE(2)) as the major factor, because inhibition of PGE(2) synthesis almost completely mitigated the immunosuppressive effects, whereas neutralization of TGF-beta, IDO, and NO activities had little effects. Moreover, the inflammatory cytokines, IFN-gamma and IL-1beta, produced by hPBMCs upon activation notably upregulated the expression of cyclooxygenase-2 (COX-2) and the production of PGE(2) by hUC-MSCs. In conclusion, our data have demonstrated for the first time the PGE(2)-mediated mechanism by which hUC-MSCs exert their immunomodulatory effects.
PMID: 20207200 [PubMed - as supplied by publisher]
Posted in: Clin Immunol
March 10th, 2010 / No Comments » / by Sweet DJ
Dealing with scientific disagreements.
Cell Stem Cell. 2010 Mar 5;6(3):183
Authors: Sweet DJ
PMID: 20207215 [PubMed - in process]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by Karayannis T, Fishell G
Inhibition as a Transplant-Mediated Therapy: A New Paradigm for Treating Parkinson's?
Cell Stem Cell. 2010 Mar 5;6(3):184-185
Authors: Karayannis T, Fishell G
In this issue of Cell Stem Cell,Martínez-Cerdeño and colleagues (2010) transplant interneuron precursors from the MGE into the striatum of a rat model of Parkinson's disease and observe a 5% increase in the endogenous GABAergic interneuron population resulting in behavioral benefits in both lesioned and wild-type animals.
PMID: 20207216 [PubMed - as supplied by publisher]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by North TE, Goessling W
NOTCHing an Arrow at Cord Blood: Translating Stem Cell Knowledge into Clinical Practice.
Cell Stem Cell. 2010 Mar 5;6(3):186-187
Authors: North TE, Goessling W
Umbilical cord transplants have emerged as an important therapeutic option for patients with leukemia and lymphoma. A recent study in Nature Medicine highlights the potential and challenges of translating cell-based therapies to the clinic.
PMID: 20207217 [PubMed - as supplied by publisher]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by Noseda M, Schneider MD
Unleashing Cardiopoiesis: A Novel Role for G-CSF.
Cell Stem Cell. 2010 Mar 5;6(3):188-189
Authors: Noseda M, Schneider MD
Identifying pathways for cardiac muscle creation is a paramount objective of cardiac stem cell biology. In this issue of Cell Stem Cell, Shimoji and colleagues (2010) report the unforeseen ability of granulocyte colony-stimulating factor (G-CSF) to drive cardiopoiesis in mouse, primate, and human pluripotent cells.
PMID: 20207218 [PubMed - as supplied by publisher]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by Issigonis M, Matunis E
Niche Today, Gone Tomorrow-Progenitors Create Short-Lived Niche for Stem Cell Specification.
Cell Stem Cell. 2010 Mar 5;6(3):191-193
Authors: Issigonis M, Matunis E
Establishing tissue-specific adult stem cells during organogenesis is important for maintenance of tissue homeostasis throughout the lifetime of the organism. In a recent study in Science, Mathur et al. (2010) describe how progenitor cells in the Drosophila larval midgut create a temporary niche to maintain stem cell fate during development.
PMID: 20207220 [PubMed - as supplied by publisher]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by Hosokawa K, Arai F, Yoshihara H, Iwasaki H, Hembree M, Yin T, Nakamura Y, Gomei Y, Takubo K, Shiama H, Matsuoka S, Li L, Suda T
Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow.
Cell Stem Cell. 2010 Mar 5;6(3):194-8
Authors: Hosokawa K, Arai F, Yoshihara H, Iwasaki H, Hembree M, Yin T, Nakamura Y, Gomei Y, Takubo K, Shiama H, Matsuoka S, Li L, Suda T
PMID: 20207221 [PubMed - in process]
Posted in: Cell Stem Cell
March 10th, 2010 / No Comments » / by Li P, Zon LI
Resolving the Controversy about N-Cadherin and Hematopoietic Stem Cells.
Cell Stem Cell. 2010 Mar 5;6(3):199-202
Authors: Li P, Zon LI
Discrepancies in published results about the role of N-cadherin in hematopoietic stem cells have led to confusion in the field. Attempting to settle the disagreements and reach a consensus, we undertook a collective discussion approach. This process clarified a number of issues but left some questions still unresolved.
PMID: 20207222 [PubMed - as supplied by publisher]
Posted in: Cell Stem Cell
