Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in the CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs) and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insufficient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs) represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and differentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in different MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment

Systemic rejuvenation: From blood to molecular therapies

With the increasing aging population, aged-related diseases are the big challenge in the 21st century. The aging organism can be considered to be in a prodromal stage, as it is only a matter of time for the first clinical symptoms to appear. Therefore, attempts to rejuvenate the aged body might not only provide us in future with “healthy aging” but might also be fundamental for therapeutic strategies to fight age-related diseases. A breakthrough for the field of rejuvenation was proof of concept experiments using an almost forgotten method, the parabiosis. Here, the blood circulation system of two individual animals gets fused, which provides a constant blood exchange between the two animals. Heterochronic parabiosis, i.e. fusing the blood system of an old with a young mouse, provided evidence that young blood rejuvenates the aged organism, for example muscle or brain tissue, and restores functions such as regeneration and learning and memory, which otherwise decline during aging. Thus, aging can be targeted through a systemic approach. Importantly, brain diseases such as Alzheimer’s dementia, which were previously considered as being isolated from the rest of the body, are now more and more seen as systemic diseases, which can be targeted through blood-borne factors or systemic approaches. Moreover, we might see age-related diseases with common mechanisms given that patients often come with co-morbidities, and a systemic rejuvenation approach might alleviate not only one but several symptoms

System modeling and dispatch schedule optimization of combined PV battery system using linear optimization

Master's thesis in Renewable energy (ENE500)Energy storage plays a vital role in paving the way for more renewable penetration. The technology is costly, but intelligent solutions regarding dispatch strategies and system design can help reduce the total cost over the projected lifetime of a system. For this thesis, a customizable linear programming algorithm is created within Python to optimize the battery energy scheduling based on generated PV power, electricity cost and load demand. The commercial system optimization tool HOMER is used to verify the code by running simulations based on historic data collected from Nord Pool and UiAs own photovoltaic system. One benefit of the custom made code is its ability to do day-ahead optimization utilizing data from APIs. To obtain forecasted irradiation and temperature data the Solcast API was used as the only paid service for the Python script to ensure market-leading accuracy

Editorial: The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration.

Editorial on the Research Topic The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration In mammals, although regeneration is quite restricted to a number of tissues and organs, this particular healing process is possible through the existence of tissue-resident stem/progenitor cells. Upon injury, these cells are activated, they proliferate, migrate, and differentiate into tissue-specific cells and functionally replace the damaged or lost cells. Besides this, angiogenesis and neovascularization play crucial roles in tissue repair. Blood vessels (BV) together with the resident surrounding cells create a vascular niche which is central to local and distant signaling thereby shaping the regenerative response. The Frontiers Research Topic “The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration” encompasses 14 articles highlighting various aspects of the vascular niche (VN) in health and disease. This research topic first describes ex vivo methodological aspects to study the role of the VN in regeneration, second addresses the VN cellular composition and roles during regeneration, third described local as well as distant signaling mechanisms regulating the VN in regeneration and, finally addresses the VN responses in pathology

Beyond Clotting: A Role of Platelets in CNS Repair?

This work was supported by the State Government of Salzburg, Austria, (Stifungsprofessur, and 20204-WISS/80/199-2014), through funding from the European Union's Seventh Framework Program (FP7/2007–2013) under grant agreements n° HEALTH-F2-2011-278850 (INMiND), n° HEALTH-F2-2011-279288 (IDEA), n° FP7-REGPOT-316120 (GlowBrain), the Austrian Science Fund FWF Special Research Program (SFB) F44 (F4413-B23) “Cell Signaling in Chronic CNS Disorders,” by the research funds from the Paracelsus Medical University PMU-FFF (Long-Term Fellowship L-12/01/001-RIV to FR and Stand Alone grant 2058).This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fncel.2015.00511

Neuroplasticity, limbic neuroblastosis and neuro-regenerative disorders

The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia

In Vivo Monitoring of Adult Neurogenesis in Health and Disease

Adult neurogenesis, i.e., the generation of new neurons in the adult brain, presents an enormous potential for regenerative therapies of the central nervous system. While 5-bromo-2′-deoxyuridine labeling and subsequent histology or immunohistochemistry for cell-type-specific markers is still the gold standard in studies of neurogenesis, novel techniques, and tools for in vivo imaging of neurogenesis have been recently developed and successfully applied. Here, we review the latest progress on these developments, in particular in the area of magnetic resonance imaging (MRI) and optical imaging. In vivo in situ labeling of neural progenitor cells (NPCs) with micron-sized iron oxide particles enables longitudinal visualization of endogenous progenitor cell migration by MRI. The possibility of genetic labeling for cellular MRI was demonstrated by using the iron storage protein ferritin as the MR reporter-gene. However, reliable and consistent results using ferritin imaging for monitoring endogenous progenitor cell migration have not yet been reported. In contrast, genetic labeling of NPCs with a fluorescent or bioluminescent reporter has led to the development of some powerful tools for in vivo imaging of neurogenesis. Here, two strategies, i.e., viral labeling of stem/progenitor cells and transgenic approaches, have been used. In addition, the use of specific promoters for neuronal progenitor cells such as doublecortin increases the neurogenesis-specificity of the labeling. Naturally, the ultimate challenge will be to develop neurogenesis imaging methods applicable in humans. Therefore, we certainly need to consider other modalities such as positron emission tomography and proton magnetic resonance spectroscopy (1H-MRS), which have already been implemented for both animals and humans. Further improvements of sensitivity and neurogenesis-specificity are nevertheless required for all imaging techniques currently available

Mesenchymal Stem Cells Promote Oligodendroglial Differentiation in Hippocampal Slice Cultures

We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naive NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS. Copyright (C) 2009 S. Karger AG, Base