Why regenerative stem cell medicine progresses slower than expected

Stem cell research has been acclaimed to revolutionize the future of medicine, and to offer new treatments for previously incurable diseases. Despite years of research, however, the therapeutic potential of stem cell research has not yet been fully realized. By June 2014, the US Food and Drug Administration had approved only five stem cell-based medicinal products, all of which cord blood derived hematopoietic stem cell products for the cure of blood and immunological diseases. Anticipated treatments for cancer, neurodegenerative disorders, gastroenterological, myocardial, and other diseases are still far from routine applications. What are the reasons for the slow progress in the stem cell field, and the mismatch between public expectations and actual achievements

Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer’s disease: a selective review

Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer’s disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer’s disease. However, neuropsychologists are attempting to meet this challenge by designing newer cognitive measures and questionnaires derived from translational efforts in neuroimaging, cognitive neuroscience and clinical/experimental neuropsychology. This review is a selective summary of several novel, potentially promising, approaches that are being explored for detecting early cognitive evidence of preclinical Alzheimer’s disease in presymptomatic individuals

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice Cancer Res 66

Access the most recent version of this article at: doi: 10.1158/0008-5472.CAN-05-2937 Access the most recent supplemental material at

Smart Cupboard for Assessing Memory in Home Environment

Sensor systems for the Internet of Things (IoT) make it possible to continuously monitor people, gathering information without any extra effort from them. Thus, the IoT can be very helpful in the context of early disease detection, which can improve peoples'' quality of life by applying the right treatment and measures at an early stage. This paper presents a new use of IoT sensor systemswe present a novel three-door smart cupboard that can measure the memory of a user, aiming at detecting potential memory losses. The smart cupboard has three sensors connected to a Raspberry Pi, whose aim is to detect which doors are opened. Inside of the Raspberry Pi, a Python script detects the openings of the doors, and classifies the events between attempts of finding something without success and the events of actually finding it, in order to measure the user''s memory concerning the objects'' locations (among the three compartments of the smart cupboard). The smart cupboard was assessed with 23 different users in a controlled environment. This smart cupboard was powered by an external battery. The memory assessments of the smart cupboard were compared with a validated test of memory assessment about face-name associations and a self-reported test about self-perceived memory. We found a significant correlation between the smart cupboard results and both memory measurement methods. Thus, we conclude that the proposed novel smart cupboard successfully measured memory

Collaboration of Smart IoT Devices Exemplified With Smart Cupboards

[EN] The variety of smart things connected to Internet hampers the possibility of having a standalone solution for service-centric provisioning in the Internet of Things (IoT). The different features of smart objects in processing capabilities, memory, and size make it difficult for final users to learn the installation and usage of all these devices in collaboration with other IoT objects, hindering the user experience. In this context, we propose a collaboration mechanism for IoT devices based on the multi-agent systems with mobile agents. This paper illustrates the current approach with smart cupboards for potentially tracking memory losses. The user study revealed that users found working products of this approach usable, easy-to-learn and useful, and they agreed that the current approach could provide a high quality of experience not only in the specific case of service-centric IoT devices for tracking memory losses but also in other domains. The learning capability by means of this approach was showed with significant reductions of reaction times and number of errors over the first and second tests with the current approach. System response timesThis work was supported in part by the Dpto. de Innovacion, Investigacion y Universidad del Gobierno de Aragon through the program FEDER Aragon 2014-2020 Construyendo Europa desde Aragon under Grant T49_17R, in part by the University of Zaragoza and the Foundation Ibercaja through the Research Project Construccion de un framework para agilizar el desarrollo de aplicaciones moviles en el ambito de la salud under Grant JIUZ-2017-TEC-03, in part by the Estancias de movilidad en el extranjero Jose Castillejo para jovenes doctores Program, Spanish Ministry of Education, Culture and Sport, under Grant CAS17/00005, in part by the Universidad de Zaragoza, Fundacion Bancaria Ibercaja and Fundacion CAI, Programa Ibercaja-CAI de Estancias de Investigacion, under Grant IT24/16 and Grant IT1/18, in part by the Research Project Desarrollo Colaborativo de Soluciones AAL, Spanish Ministry of Economy and Competitiveness, under Grant TIN2014-57028-R, in part by the Organismo Autonomo Programas Educativos Europeos under Grant 2013-1-CZ1-GRU06-14277, and in part by the Ministerio de Economia y Competitividad through the Programa Estatal de Fomento de la Investigacion Cientifica y Tecnica de Excelencia, Subprograma Estatal de Generacion de Conocimiento, under Grant TIN2017-84802-C2-1-P.García-Magariño, I.; González-Landero, F.; Amariglio, R.; Lloret, J. (2019). Collaboration of Smart IoT Devices Exemplified With Smart Cupboards. IEEE Access. 7:9881-9892. https://doi.org/10.1109/ACCESS.2018.2890393S98819892

Head-mounted display-based application for cognitive training

Virtual Reality (VR) has had significant advances in rehabilitation, due to the gamification of cognitive activities that facilitate treatment. On the other hand, Immersive Virtual Reality (IVR) produces outstanding results due to the interactive features with the user. This work introduces a VR application for memory rehabilitation by walking through a maze and using the Oculus Go head-mounted display (HMD) technology. The mechanics of the game require memorizing geometric shapes while the player progresses in two modes, autonomous or manual, with two levels of difficulty depending on the number of elements to remember. The application is developed in the Unity 3D video game engine considering the optimization of computational resources to improve the performance in the processing and maintaining adequate benefits for the user, while the generated data is stored and sent to a remote server. The maze task was assessed with 29 subjects in a controlled environment. The obtained results show a significant correlation between participants’ response accuracy in both the maze task and a face–pair test. Thus, the proposed task is able to perform memory assessments

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities