Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves

Heine, Walter F.; Conant, Katherine; Griffin, John W.; Höke, Ahmet

doi:10.1016/j.expneurol.2004.06.014

Cited by 154 publications

(103 citation statements)

References 55 publications

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“…This protease enhances neurite outgrowth of dorsal root ganglionic neurons on peripheral nerve explants by degrading a still unidentified CSPG, which may otherwise inhibit laminin-promoted neurite extension (Zuo et al, 1998). Likewise, peripheral nerve segments, predegenerated by endogenous MMP-2 or neural stem cellproduced MMP-2, support axonal regeneration as a result of CSPG degradation (Krekoski et al, 2002;Heine et al, 2004).…”

Section: Inhibitory Cspgs and Mmpsmentioning

confidence: 99%

Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Hsu¹,

McKeon²,

Goussev³

et al. 2006

J. Neurosci.

204

184

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Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in both injury and repair mechanisms in the CNS. Pharmacological blockade of MMPs, limited to the first several days after spinal cord injury, improves locomotor recovery. This beneficial response is, however, lost when treatment is extended beyond the acutely injured cord to include wound healing and tissue remodeling. This suggests that some MMPs play a beneficial role in wound healing. To test this hypothesis, we investigated the role of MMP-2, which is actively expressed during wound healing, in white matter sparing and axonal plasticity, the formation of a glial scar, and locomotor recovery after spinal cord injury. MMP-2 increased between 7 and 14 d after injury, where it was immunolocalized in reactive astrocytes bordering the lesion epicenter. There was reduced white matter sparing and fewer serotonergic fibers, caudal to the lesion in injured MMP-2 null animals. MMP-2 deficiency also resulted in increased immunoreactivity to chondroitin sulfate proteoglycans and a more extensive astrocytic scar. Most importantly, locomotion in an open field, performance on a rotarod, and grid walking were significantly impaired in injured MMP-2 null mice. Our findings suggest that MMP-2 promotes functional recovery after injury by regulating the formation of a glial scar and white matter sparing and/or axonal plasticity. Thus, strategies exploiting MMPs as therapeutic targets must balance these beneficial effects during wound healing with their adverse interactions in the acutely injured spinal cord.

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Section: Inhibitory Cspgs and Mmpsmentioning

confidence: 99%

Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Hsu¹,

McKeon²,

Goussev³

et al. 2006

J. Neurosci.

204

184

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“…13 NSCs derived from various sources have been found to elute nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glialderived neurotrophic factor (GDNF), and matrix metalloprotease-2, which degrades chondroitin sulfate proteoglycan (a molecule inhibitory to axonal growth). 6,[13][14][15] Thus, NSCs and progenitor cells may be exploited as a sort of miniature drug factory, releasing factors that result in the desired healing response in injured nervous tissue. Encapsulation of these cells in alginate may further enhance their therapeutic utility by localizing the cells to the site of injury and isolating them from a host immune response.…”

Section: Introductionmentioning

confidence: 99%

“…9,11,12 Several studies suggest that NSCs have an innate ability to promote neuroprotection and axonal regeneration of host tissue. 11,[13][14][15][16] Potential mechanisms include constitutive secretion of multiple neurotrophic factors, 11,[14][15][16] as well as degrading molecules that are inhibitory to axonal growth. 13 NSCs derived from various sources have been found to elute nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glialderived neurotrophic factor (GDNF), and matrix metalloprotease-2, which degrades chondroitin sulfate proteoglycan (a molecule inhibitory to axonal growth).…”

Section: Introductionmentioning

confidence: 99%

“…11,[13][14][15][16] Potential mechanisms include constitutive secretion of multiple neurotrophic factors, 11,[14][15][16] as well as degrading molecules that are inhibitory to axonal growth. 13 NSCs derived from various sources have been found to elute nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glialderived neurotrophic factor (GDNF), and matrix metalloprotease-2, which degrades chondroitin sulfate proteoglycan (a molecule inhibitory to axonal growth). 6,[13][14][15] Thus, NSCs and progenitor cells may be exploited as a sort of miniature drug factory, releasing factors that result in the desired healing response in injured nervous tissue.…”

Section: Introductionmentioning

confidence: 99%

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Alginate Composition Effects on a Neural Stem Cell–Seeded Scaffold

Purcell

Singh

Kipke

2009

Tissue Engineering Part C: Methods

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The purpose of this study was to evaluate the effects of alginate composition on the neurotrophic factor release, viability, and proliferation of encapsulated neural stem cells (NSCs), as well as on the mechanical stability of the scaffold itself. Four compositions were tested: a high guluronic acid (68%) and a high mannuronic acid (54%) content alginate, with or without a poly-L-lysine (PLL) coating layer. Enzyme-linked immunosorbent assay was used to quantify the release of brain-derived neurotrophic factor, glial-derived neurotrophic factor, and nerve growth factor from the encapsulated cells. All three factors were detected from encapsulated cells only when a high L-guluronic acid alginate without PLL was used. Additionally, capsules with this composition remained intact more frequently when exposed to solutions of low osmolarity, potentially indicating superior mechanical stability. Alginate beads with a PLL-coated, high D-mannuronic acid composition were the most prone to breakage in the osmotic pressure test, and were too fragile for histology and proliferation assays after 1 week in vitro. NSCs survived and proliferated in the three remaining alginate compositions similarly over the 21-day study course irrespective of scaffold condition. NSC-seeded alginate beads with a high L-guluronic acid, non-PLL-coated composition may be useful in the repair of injured nervous tissue, where the mechanism is the secretion of neuroprotective factors. We verify the neuroprotective effects of medium conditioned by NSCseeded alginate beads on the serum withdrawal-mediated death of PC-12 cells here.

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“…Murakami et al (2003) have used a silicone tube enriched with transplanted NSCs for repairing rat nerve defects and found that this approach promote axonal regeneration. Transplantation of NSCs were also found to promote axonal regeneration after chronical transection of rat nerves (Heine et al, 2004).…”

Section: Tissue Engineering Of Peripheral Nervesmentioning

confidence: 99%

Perspectives in regeneration and tissue engineering of peripheral nerves

Raimondo

Fornaro

Tos

et al. 2011

Annals of Anatomy - Anatomischer Anzeiger

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S u m m a r yPeripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined.

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Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves

Cited by 154 publications

References 55 publications

Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Matrix Metalloproteinase-2 Facilitates Wound Healing Events That Promote Functional Recovery after Spinal Cord Injury

Alginate Composition Effects on a Neural Stem Cell–Seeded Scaffold

Perspectives in regeneration and tissue engineering of peripheral nerves

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