Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis

Einstein, Ofira; Karussis, Dimitrios; Grigoriadis, Nikolaos; Mizrachi-Kol, Rachel; Reinhartz, Etti; Abramsky, Oded; Ben‐Hur, Tamir

doi:10.1016/j.mcn.2003.08.009

Cited by 214 publications

(187 citation statements)

References 47 publications

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“…27 Isolation of neural precursors and growth of neurospheres. This procedure is based on the studies of Ben-Hur et al 28,29 For the derivation of neural progenitors, newborn (PN1-PN2) HS/Ibg mice were used. Cerebral cortices were minced, digested in 0.025% trypsin for 20 min and dissociated with a 5 ml Sphere transplantation.…”

Section: Specific Methodsmentioning

confidence: 99%

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

2007

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Grafting of neural progenitors has been shown to reverse a wide variety of neurobehavioral defects. While their role of replacing injured cells and restoring damaged circuitries has been shown, it is widely accepted that this cannot be the only mechanism, as therapy can occur even when an insufficient number of transplanted cells are found. We hypothesized that one major mechanism by which transplanted neural progenitors exert their therapeutic effect is by enhancing endogenous cells production. Consequently, in an allographic model of transplantation, prenatally heroin-exposed genetically heterogeneous (HS) mice were made defective in their hippocampal neurobehavioral function by exposing their mothers to heroin (10 mg kg À1 heroin on gestation days 9-18). Hippocampal damage was confirmed by deficient performance in the Morris maze (P < 0.009), and decreased production of endogenous cells in the dentate gyrus by 39% was observed. On postnatal day 35, they received an HS-derived neural progenitors transplant followed by repeated bromodeoxyuridine injections. The transplant returned endogenous cells production to normal levels (P < 0.006) and reversed the behavioral defects (P < 0.03), despite the fact that only 0.0334% of the transplanted neural progenitors survived and that they differentiated mainly to astrocytes. An immunological study demonstrated the presence of macrophages and T cells as a possible explanation for the paucity of the transplanted cells. This study suggests one mechanism for the therapeutic action of neural progenitors, the enhancement of the production of endogenous cells, pointing to future clinical applications in this direction by use of neural progenitors or by analogous cell-inducing techniques.

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Section: Specific Methodsmentioning

confidence: 99%

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

2007

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“…The first indication of a novel anti-inflammatory effect of NPCs was obtained when neurospheres were transplanted intracerebroventricularly (ICV) in acute spinal cord homogenate-induced EAE Lewis rats [171]. This model manifests with acute reversible paralytic disease that is the result of disseminated CNS inflammation without demyelination or axonal injury [172].…”

Section: Immune Modulationmentioning

confidence: 99%

“…This model manifests with acute reversible paralytic disease that is the result of disseminated CNS inflammation without demyelination or axonal injury [172]. NPC transplantation in spinal cord homogenate-induced EAE Lewis rats attenuated the inflammatory brain process and clinical severity of disease [171]. Follow-up studies examined the effect of NPC transplantation on either ICV or intravenous cell injection in the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide-induced EAE in C57BL/6 mice.…”

Section: Immune Modulationmentioning

confidence: 99%

“…Alternatively, it has been suggested that NPCs inhibit T-cell activation and proliferation by a nonspecific, bystander immune suppressive action [177]. This notion emerged from co-culture experiments that showed a striking inhibition of the activation and proliferation of EAE-derived, as well as naive, T cells by NPCs, following stimulation by various stimuli [171,177,179]. The suppressive effect of NPCs on T cells was accompanied by a significant suppression of proinflammatory cytokines, such as interleukin (IL)-2, tumor necrosis factor-α, and interferon-γ [177].…”

Section: Immune Modulationmentioning

confidence: 99%

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Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

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“…The term 'neural progenitor cell' (NPC) will be used here to include both neural stem and progenitor cells. Neural progenitor cells are excellent candidates for cellular transplantation therapy because they have been shown to replace dead or dying neural tissue, elaborate trophic factors to rescue dysfunctional endogenous neurons, inhibit inflammation, and deliver therapeutic proteins in a widely disseminated manner (Snyder et al, 1995;Lacorazza et al, 1996;Ourednik et al, 2002;Einstein et al, 2003;Pluchino et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

In vitro growth and differentiation of canine olfactory bulb-derived neural progenitor cells under variable culture conditions

Walton

Wolfe

2008

Journal of Neuroscience Methods

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The dog serves as a large animal model for multiple neurologic diseases that may potentially benefit from neural progenitor cell (NPC) transplantation. In the adult brain, multipotent NPCs reside in the subventricular zone and its rostral and caudal extensions into the olfactory bulb and hippocampus. The olfactory bulb represents a surgically accessible site for obtaining cells for autologous NPC transplantation. To model conditions that would occur for ex vivo gene therapy in the postnatal brain, NPCs were isolated from the canine olfactory bulb, expanded ex vivo under different culture conditions, and compared quantitatively for growth and immunophenotype. Under standard growth conditions, canine olfactory bulb-derived NPCs (OB-cNPCs) could be expanded nearly 500-fold in the time evaluated. Canine OB-cNPCs grown on poly-D-lysine (PDL) or on PDL-fibronectin had similar growth rates, whereas supplementation with leukemia inhibitory factor (LIF) resulted in significantly slower growth. However, when OB-cNPC cultures were grown on PDL-fibronectin or PDL supplemented with LIF, a greater proportion of cells with neuronal markers were generated upon differentiation.

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Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis

Cited by 214 publications

References 47 publications

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

Cell Therapy for Multiple Sclerosis

In vitro growth and differentiation of canine olfactory bulb-derived neural progenitor cells under variable culture conditions

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