Cell-based therapeutic strategies for multiple sclerosis.

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials

Cell-based therapies for stroke : promising solution or dead end?

The introduction of recanalization procedures has revolutionized acute stroke management, although the narrow time window, strict eligibility criteria and logistical limitations still exclude the majority of patients from treatment. In addition, residual deficits are present in many patients who undergo therapy, preventing their return to premorbid status. Hence, there is a strong need for novel, and ideally complementary, approaches to stroke management. In preclinical experiments, cell-based treatments have demonstrated beneficial effects in the subacute and chronic stages following stroke [1; 2; 3] and therefore are considered a promising option to supplement current clinical practice. At the same time, great progress has been made in developing clinically feasible delivery and monitoring protocols [4]. However, efficacy results initially reported in clinical studies fell short of expectations [5] raising concerns that cell treatment might eventually share the ‘dead end fate’ of many previous experimental stroke therapies. This Research Topic reviews some of the latest and most innovative studies to summarize the state of the art in translational cell treatments for stroke

Memory cell based on a φ\varphi Josephson junction

The $\varphi$ Josephson junction has a doubly degenerate ground state with the Josephson phases $\pm\varphi$. We demonstrate the use of such a $\varphi$ Josephson junction as a memory cell (classical bit), where writing is done by applying a magnetic field and reading by applying a bias current. In the "store" state, the junction does not require any bias or magnetic field, but just needs to stay cooled for permanent storage of the logical bit. Straightforward integration with Rapid Single Flux Quantum logic is possible.Comment: to be published in AP

Cell-based gene therapy for mending infarcted hearts

The goal of this study was to analyse the efficiency of a combinatorial cell/growth factor therapy to improve function of infarcted murine hearts. The Insulin-like Growth Factor-1 (IGF-1) isoform, IGF-1Ea, has been shown to reduce scar formation and decrease cell death after MI. The present study utilized P19Cl6-derived, IGF-1Ea over-expressing cardiomyocytes to achieve its goal. The P19Cl6 cells were stably transduced with IGF-1Ea using a lentiviral vector and investigated first in vitro for their feasibility for in vivo cell therapy. The engineered pluripotent cells over-expressing IGF-1Ea survived better to hypoxia-induced injury than the control cells. The cells maintained their pluripotency and efficient differentiation capacity towards ventricular cardiomyocyte lineage, generating large quantities of cardiomyocytes optimal for the transplantation study. The generated cardiomyocytes were functionally active and exhibited a mature phenotype. Transplantation of the cardiomyocytes into allogeneic wild type murine infarcted hearts conferred a tendency for maintenance of function at short-term time point. At long-term however, this effect was lost, returning to the level of the control infarcted hearts. Cell tracing assessment revealed engraftment of both IGF-1Ea- and empty-cells, although the cells failed to couple with the recipient tissue. Scar size and capillary density analyses revealed no significant difference between the cells transplanted compared to the saline treated hearts, corroborating with the long-term functional data. Interestingly, the IGF- 1Ea-cell transplanted hearts expressed significantly higher amount of VEGFa compared to the controls, albeit no change in capillary density. Further investigation revealed that the enhanced VEGFa expression in IGF-1Ea-cells transplanted hearts was associated with reduced hypertrophy, marked by reduced cell cross-sectional area at the border-zone, aSK and bMHC expression compared to the control hearts. Nonetheless, modulation of hypertrophic response and transplantation of IGF-1Ea-cells were not able to confer lasting functional preservation, possibly due to lack of sufficient engraftment and coupling of the transplanted cells

Mesenchymal stem cell-based therapy for ischemic stroke

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field

Cell-based approach for 3D reconstruction from incomplete silhouettes

Shape-from-silhouettes is a widely adopted approach to compute accurate 3D reconstructions of people or objects in a multi-camera environment. However, such algorithms are traditionally very sensitive to errors in the silhouettes due to imperfect foreground-background estimation or occluding objects appearing in front of the object of interest. We propose a novel algorithm that is able to still provide high quality reconstruction from incomplete silhouettes. At the core of the method is the partitioning of reconstruction space in cells, i.e. regions with uniform camera and silhouette coverage properties. A set of rules is proposed to iteratively add cells to the reconstruction based on their potential to explain discrepancies between silhouettes in different cameras. Experimental analysis shows significantly improved F1-scores over standard leave-M-out reconstruction techniques

Two-dimensional interpolation using a cell-based searching procedure

In this paper we present an efficient algorithm for bivariate interpolation, which is based on the use of the partition of unity method for constructing a global interpolant. It is obtained by combining local radial basis function interpolants with locally supported weight functions. In particular, this interpolation scheme is characterized by the construction of a suitable partition of the domain in cells so that the cell structure strictly depends on the dimension of its subdomains. This fact allows us to construct an efficient cell-based searching procedure, which provides a significant reduction of CPU times. Complexity analysis and numerical results show such improvements on the algorithm performances