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Human iPSC-derived Neural Stem Cells Promote Functional Recovery after Stroke

Researchers find that neural stem cells derived from induced pluripotent stem cells may represent an important new strategy for the treatment of acute stroke.

Remyelination Rules for Stem Cell Spinal Cord Injury Repair

Detailed analysis in mice finds that the main mode by which neural stem cells mediate recovery after spinal cord injury is through the remyelination of damaged host axons.

From Rodents to Non-Human Primates - NSPCs aid Functional Recovery after Spinal Cord Injury

A new study in a clinically relevant non-human primate model finds that neural stem/progenitor cells mediate functional recovery after transplantation into the injured spinal cord

Supportive Microcarriers Boost Stem Cell-Based Therapy for Parkinson ’s disease

Researchers find that pharmacologically active microcarriers which mediate the release of Neurotrophin 3 improve stem cell treatment in a model of Parkinsons’ Disease

Analyses of Immunosuppressants Effect on NSCs Therapeutic Function

Stem cell therapy in humans currently relies on the use of immunosuppressants to ensure long-term cell survival and function.

Spinal Cord Treatment Problems – Site not the Cells?

Therapeutic Activities of Engrafted Neural Stem/Precursor Cells Are Not Dormant in the Chronically Injured Spinal Cord

From Stem Cells

Neural stem or precursor cells (NSPCs) have tremendous promise for use in cell-based therapies for the treatment of spinal cord injury (SCI) as they have been shown to provide trophic support following transplantation, allowing modification of the host environment to allow some endogenous regeneration and repair in animal models (Aboody et al, Barnabe-Heider and Frisen, and Martino and Pluchino).   However, few studies have assessed their role in the chronic phase of SCI (Tetzlaff et al) and any correlation to microenvironmental factors (Thuret et al), which is potentially important for the behaviour of transplanted NSPCs.   Now, in a study published in Stem Cells from the laboratory of Seiji Okada at Kyushu University, Japan, Kumamaru et al combine flow-cytometric isolation and RNA-Seq to analyse the transcriptome of NSPCs transplanted into SCI during the chronic phase, and have demonstrated that while the cells have a positive therapeutic effect, the refractory state of the chronically injured spinal cord hampers locomotory recovery.

Explosive research reveals the dynamics of adult human neurogenesis

Original paper “Dynamics of Hippocampal Neurogenesis in Adult Humans” from Cell by Spalding et al.

In the last two decades the central dogma which dictated that no new neurons are born in the adult brain has been refuted, and the mammalian subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of the hippocampal dentate gyrus are now recognised sites of adult neurogenesis.   Newborn neurons from the SVZ migrate to the olfactory bulb to provide new granule cell neurons throughout life and adult-born hippocampal neurons are implicated in pattern separation (the ability to form and use memories arising from similar stimuli) and memory formation.   Yet while some evidence exists for this capacity in adult humans, the dynamics and functional contribution of these newly generated cells to brain function still elicits strong scientific debate.   An innovative technique1 developed by Kirsty Spalding and Jonas Frisen at the Karolinska Institute in Stockholm, Sweden, which utilises the radioactive carbon 14 isotope (14C) curve created by the dramatic increase in atmospheric 14C levels following above-ground nuclear bomb testing during the Cold War and subsequent decline following the Partial Nuclear Test Ban Treaty in 1963, has now been used to examine the cell turnover dynamics of the adult human hippocampus.2   Their method takes advantage of the fact that new cells incorporate 14C into their genomic DNA at a concentration that mirrors atmospheric 14C at the time of their birth, creating a ‘date mark’ in the DNA.   Extrapolation of 14C concentration to the atmospheric 14C curve can therefore allow the accurate determination of the period during which a cell was born.   In their article recently published in Cell, Spalding et al.2 report their findings and reveal that a surprising proportion of human neural cells are subject to turnover, which may indicate a cognitive role for these newly generated adult cells.

Nestin Mediated NSC Purification

“Lineage-Specific Purification of Neural Stem-Progenitor Cells from Differentiated Mouse Induced Pluripotent Stem Cells”

From Stem Cells Translational Medicine.

While protocols for the differentiation of specific cell lineages from pluripotent cell types abound; the problem of the purification of these cells still remains unsolved.   Problems include the presence of remaining pluripotent stem cells in differentiated cultures which may cause tumourigenesis and the presence of other unwanted cell types.   To get around this problem, fluorescence-activated cell sorting (FACS) (Fukuda et al and Ladewig et al) or drug selection strategies (Li et al) have been proposed and used.   FACS purification of neural stem cells (NSCs) is difficult as many markers are not cell surface antigens (Lendahl et al and Kaneko et al), and so researchers from the laboratory of Tetsuo Sugimoto at the Kansai Medical University, Osaka, Japan have utilised a drug selection strategy, as is reported in Stem Cells Translational Medicine.   Using Nestin regulatory sequences in a rat model they report the successful isolation of pure NSCs using drug selection (Maruyama et al).

In pursuit of the optimal graft site for spinal cord injury

Original article from STEM CELLS TRANSLATIONAL MEDICINE

 “Safety of epicentre versus intact parenchyma as a transplantation site for human neural stem cells for spinal cord injury therapy”

The ability to successfully replace lost or dysfunctional neurons of the central nervous system (CNS) by transplanting de novo cells is an on-going pursuit which represents one of the only therapeutic possibilities for functional restoration in many forms of neural trauma and disease. The complex nature of the CNS microenvironment however makes this an arduous task. This is especially true for spinal cord injury (SCI), where multiple differing layers of damage exist around the core of the insult, and reconstitution not only requires the replacement of damaged cells, but long distance axonal regeneration along growth-inhibitory tracts and the establishment of topographically correct connections once the target has been reached. Further, the epicentre of the injury becomes ‘shut off’ by a glial scar, which encloses the centre of damage to limit inflammation and restores the integrity of the blood-brain barrier, but unfortunately also makes the core of the injury inaccessible for any regeneration to occur. Nonetheless, the epicenter represents an easily accessible site for the delivery of new cells, and avoids additional damage to remaining healthy spinal tissue. Human CNS-derived stem cells (hCNS-SCns) can be enriched from 16-20 week foetal brain tissue by FACS sorting for the CD133+CD24-/lo population. Studies have previously reported that hCNS-SCns transplanted both rostral and caudal to a SCI in immunocompromised NOD-scid mice can differentiate into oligodendrocytes capable of myelination which can improve locomotor function.1-3 In a recent study, which has emerged from multiple centres in California and is published in Stem Cells Translational Medicine, following on from this previous work Piltti et al.4 have directly compared the transplantation of hCNS-SCns into intact parenchyma adjacent to the injury epicentre, or into the epicenter itself, in an adult rat model of contusion SCI. Their results reveal that there are still lessons to be learnt about the impact of the host immune system and graft location upon the behaviour of transplanted cells. 

NPs OK for ALS

“Neural Progenitors Derived From Human Induced Pluripotent Stem Cells Survive and Differentiate Upon Transplantation into a Rat Model of Amyotrophic Lateral Sclerosis”

From Stem Cells Translational Medicine

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which ultimately leads to death by failure of the respiratory muscles at 3–5 years post-diagnosis (Mitchell and Borasio). Currently, there are no effective treatments or preventive strategies in humans although stem-cell-based therapies may represent a possible solution. However studies which evaluated bone marrow-derived-human mesenchymal stem cells and human umbilical cord blood cells showed little or no therapeutic benefit (Lindvall and Kokaia). Additionally, while studies have described the generation of induced pluripotent stem cells (iPSCs) from ALS patients and their differentiation into motor neurons for ALS disease modeling (Bilican et al, Dimos et al, Egawa et al and Mitne-Neto et al), there has been no description of their fate after transplantation. To this end, researchers from the laboratory of Delphine Bohl (Institut Pasteur, Paris, France) and Roland Pochet (Université Libre de Bruxelles, Brussels, Belgium) have studied the intraparenchymal transplantation of human iPSC-derived neural progenitors (iPSC-NPs) into an ALS environment and report their successful differentiation into human mature neurons, some having motoneuronal morphologies, in the grey matter of the brain (Popescu et al).

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