Cell-based transplantation strategies to promote plasticity following spinal cord injury

Ruff, Crystal A.; Wilcox, Jared T.; Fehlings, Michael G.

doi:10.1016/j.expneurol.2011.02.010

Cited by 130 publications

(112 citation statements)

References 190 publications

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“…'Combinatorial' neural tissue engineering strategies have been suggested to be essential to promote various aspects of neural regeneration (such as nerve fiber regeneration, suppression of scar formation and immune responses, promotion of blood vessel growth) within the complex, multi-faceted pathology of SCI [36][37][38][39][40]. Such synergistic approaches have the potential to regenerate the injured spinal cord with varying degrees of efficacy, but none have been successfully translated into the clinic [41].…”

Section: Discussionmentioning

confidence: 99%

An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, biocompatibility, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a novel solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofiber meshes (± poly-lysine + laminin coating) within injury sites using a lightweight

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Section: Discussionmentioning

confidence: 99%

An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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“…Recent advances in acute management have drastically reduced mortality rates and contributed to an increased lifespan for SCI patients; at the same time, however, this progress in medicine has led to increased morbidity in patients who survive after SCI, because effective treatments have not been established. There is, therefore, a great demand for therapeutic developments for chronic SCI in clinical practice [3].…”

Section: Introductionmentioning

confidence: 99%

“…Based on considerable experimental evidences, clinical trials for SCI have been performed or initiated [5,6,10], and stem cell-based therapies using NSPCs are now being translated to patients with chronic SCI [6,11,12]. However, while emerging evidence supports the therapeutic potential of NSPC transplantation for the acute and subacute phases of SCI [4,5,13], few studies have investigated NSPC transplantation for the chronic phase of SCI [14] and its therapeutic efficacy for chronic SCI thus remains controversial [3,14,15].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for many neurodegenerative disorders including spinal cord injury (SCI) because it provides for neural replacement or trophic support. This strategy is now being extended to the treatment of chronic SCI patients. However, understanding of biological properties of chronically transplanted NSPCs and their surrounding environments is limited. Here, we performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factorenriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, NSPCs transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow cytometry, and their whole transcriptomes were compared by RNA sequencing. This analysis revealed that NSPCs produced many regenerative/ neurotrophic molecules irrespective of transplantation timing, and these activities were prominent in chronically transplanted NSPCs. Furthermore, chronically injured spinal cords permitted engrafted NSPCs to differentiate into neurons/oligodendrocytes and provided more neurogenic environment for NSPCs than other environments. Despite these results demonstrate that transplanted NSPCs have adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules in chronic SCI microenvironments, they did not improve locomotor function. Our results indicate that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell-based therapies into chronic SCI patients.

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“…This facilitated cell survival and axonal regeneration. In general, it is accepted that combined treatment may be more effective [64][65][66] .…”

Section: Discussionmentioning

confidence: 99%

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

Yang

Zhang

et al. 2017

Acta Pharmacol Sin

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The adult mammalian CNS has a limited capacity to regenerate after traumatic injury. In this study, a combinatorial strategy to promote axonal regeneration and functional recovery after spinal cord injury (SCI) was evaluated in adult rats. The rats were subjected to a complete transection in the thoracic spinal cord, and multichannel scaffolds seeded with activated Schwann cells (ASCs) and/or rat bone marrow-derived mesenchymal stem cells (MSCs) were acutely grafted into the 3-mm-wide transection gap. At 4 weeks posttransplantation and thereafter, the rats receiving scaffolds seeded with ASCs and MSCs exhibited significant recovery of nerve function as shown by the Basso, Beattie and Bresnahan (BBB) score and electrophysiological test results. Immunohistochemical analyses at 4 and 8 weeks after transplantation revealed that the implanted MSCs at the lesion/graft site survived and differentiated into neuron-like cells and co-localized with host neurons. Robust bundles of regenerated fibers were identified in the lesion/graft site in the ASC and MSC co-transplantation rats, and neurofilament 200 (NF) staining confirmed that these fibers were axons. Furthermore, myelin basic protein (MBP)-positive myelin sheaths were also identified at the lesion/graft site and confirmed via electron microscopy. In addition to expressing mature neuronal markers, sparse MSC-derived neuron-like cells expressed choline acetyltransferase (ChAT) at the injury site of the ASC and MSC co-transplantation rats. These findings suggest that co-transplantation of ASCs and MSCs in a multichannel polymer scaffold may represent a novel combinatorial strategy for the treatment of spinal cord injury.

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Cell-based transplantation strategies to promote plasticity following spinal cord injury

Cited by 130 publications

References 190 publications

An in vitro spinal cord injury model to screen neuroregenerative materials

An in vitro spinal cord injury model to screen neuroregenerative materials

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

Multichannel polymer scaffold seeded with activated Schwann cells and bone mesenchymal stem cells improves axonal regeneration and functional recovery after rat spinal cord injury

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