Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery

Hofstetter, Christoph P.; Schwarz, Emily; Hess, David A.; Widenfalk, Johan; Manira, Abdeljabbar El; Prockop, Darwin J.; Olson, Lar̀s

doi:10.1073/pnas.042678299

Cited by 891 publications

(674 citation statements)

References 44 publications

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“…These cells can be noninvasively isolated from a patient, rapidly expanded in vitro, transduced to express therapeutic agents and transplanted without the need for immunosuppression. Numerous studies have used these non-neural cells as a means of bridging the lesion cavity, as well as providing extracellular matrix proteins and trophic support for regeneration [23,[59][60][61][62][63][64][65][66][67][68]. Although these cells are unable to initiate myelination of regenerated axons themselves, neurotrophin production by transplanted cells leads to robust graft infiltration by endogenous Schwann cells, which may act to promote or stabilize axonal regeneration in a secondary manner [63,65,69,70].…”

Section: Provision Of Growth-promoting Substrates To Sites Of Injurymentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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Spinal cord injury permanently disrupts neuroanatomical circuitry and can result in severe functional deficits. These functional deficits, however, are not immutable and spontaneous recovery occurs in some patients. It is highly likely that this recovery is dependent upon spared tissue and the endogenous plasticity of the central nervous system. Neurotrophic factors are mediators of neuronal plasticity throughout development and into adulthood, affecting proliferation of neuronal precursors, neuronal survival, axonal growth, dendritic arborization and synapse formation. Neurotrophic factors are therefore excellent candidates for enhancing axonal plasticity and regeneration after spinal cord injury. Understanding growth factor effects on axonal growth and utilizing them to alter the intrinsic limitations on regenerative growth will provide potent tools for the development of translational therapeutic interventions for spinal cord injury.Keywords Neurotrophin . spinal cord injury . regeneration . axon plasticity . functional recovery Human Spinal Cord InjuryTraumatic injury of the spinal cord can produce a range of debilitating effects and permanently alter the capabilities and quality of life of its surviving victims. Damage to the central nervous system (CNS) in general results in destruction of neuronal circuitry. Contusion, compression, and penetration injuries of the spinal cord can interrupt the flow of sensory and motor information between the brain and periphery [1]. Depending on the location and severity of the injury, deficits can range from weakness of limb movement to total paralysis and ventilator-assisted respiration. Spontaneous functional recovery is limited, but can and often does occur in patients with initial sparing of sensorimotor function [2]. This recovery, which plateaus between 12 to 18 months, is very likely due to sparing and sprouting of axons within the zone of partial preservation, an area where some motor function remains intact, immediately adjacent to the lesion site [2].Approximately 40% of humans that sustain spinal cord injury (SCI) exhibit improvement from their early postinjury baseline, and this spontaneous recovery can range from modest to extensive [2]. Spontaneous recovery primarily appears to depend on the extent of tissue sparing at the injury site, allowing compensatory axonal sprouting and systems reorganization at levels ranging from the spinal cord to the cerebral cortex [3][4][5][6][7][8][9][10]. However, in cases of more severe injuries, means of enhancing endogenous levels of axonal sprouting and inducing true axonal regeneration are required to enhance functional outcomes.Electronic supplementary material The online version of this article

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Section: Provision Of Growth-promoting Substrates To Sites Of Injurymentioning

confidence: 99%

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Hollis

Tuszynski

2011

Neurotherapeutics

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“…Rat MSCs have been reported to bridge the epicenter of an SCI. 54 Evaluating the effect of different bone marrow cell (BMC) populations on morphological and functional recovery after …”

Section: Stem Cells In Cnsmentioning

confidence: 99%

Migration, fate and in vivo imaging of adult stem cells in the CNS

Syková

Jendelová

2007

Cell Death Differ

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“…cardiomyocytes [7][8][9], hepatocytes [10,11], and endothelial cells [12]. Especially, a large of body of evidence have indicated that mouse, rat, and human bone marrow MSCs can be induced to differentiate to neuron-like cells in culture [13][14][15][16] and further verified by the transplantation experiments in animal models of Parkinson's disease [17], stroke [18,19], cerebral ischemia [20], spinal cord injury [21], and Niemann-Pick disease [22]. However, despite many transplantation studies showing beneficial effects, most studies report low levels of cell persistence and neuronal differentiation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

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Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery

Cited by 891 publications

References 44 publications

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Neurotrophins: Potential Therapeutic Tools for the Treatment of Spinal Cord Injury

Migration, fate and in vivo imaging of adult stem cells in the CNS

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

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