Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury

Zhang, Shuxin; Huang, Fengfa; Gates, Mary; White, Jason T.; Holmberg, Eric G.

doi:10.1016/j.jneumeth.2010.06.022

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…Paralleling the synergistic increase in trophins in this group, a synergistic increase in inflammatory mediator expression was also seen. It is possible that this could be a physical or chemical effect of trophin infusion [127][128][129]. Given the inter-relationship of NGF and the inflammatory cascade [67,71], it is possible that the increase in trophin response and the increase in inflammatory mediators is inter-related.…”

Section: Expression Of Inflammatory Mediators Following Cellular Tranmentioning

confidence: 99%

An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

Hawryluk

Mothe

Wang

et al. 2012

Stem Cells and Development

151

118

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Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β1 (TGF-β1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion. Trophins may contribute to the benefits associated with cell-based repair strategies for spinal cord injury.

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Section: Expression Of Inflammatory Mediators Following Cellular Tranmentioning

confidence: 99%

An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

Hawryluk

Mothe

Wang

et al. 2012

Stem Cells and Development

151

118

View full text Add to dashboard Cite

show abstract

“…The completely transected spinal cord model was established in rats according to a previously described protocol (9). Rats were anesthetized using 3.5% pentobarbital (1.3 ml/100 g) via intraperitoneal injection, and then the T10 spinous process segments were exposed under sterile conditions (10). Completely lifted the spinal cord with the blunt crochet, the T10 segment was cut in addition to the dura and spinal cord tissue using a scalpel at two positions to isolate a 1-mm spinal segment.…”

Section: Introductionmentioning

confidence: 99%

Neural stem cell transplantation combined with erythropoietin for the treatment of spinal cord injury in rats

Zhao

Zuo

Jiang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group). Morphological alterations associated with axonal regeneration were detected using neurofilament (NF)-200 immunohistochemistry and immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB) scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats died following surgery, including 2 control rats and 1 rat each in the EPO, NSC and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have survived and migrated in the spinal cord tissue after 8 weeks. Significant histomorphological differences were observed in the NSC and NSC + EPO groups compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO group exhibited significantly enhanced axonal regeneration in the SCI area compared with the NSC group rats. The rats of the NSC and NSC + EPO groups exhibited significantly improved BBB scores compared with the EPO and control group rats at 7 days after treatment (P<0.05).In addition, the BBB scores of the NSC + EPO group were significantly improved compared with those of the three other groups at 7 days after surgery (P<0.05). Therefore, the results of the present study suggest that NSC transplantation combined with intraperitoneal injection of EPO may benefit the survival and regeneration of injured axons, and accelerate the repair of injured spinal cord tissue, thus facilitating the functional recovery of hindlimb locomotor function in rats.

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“…The viral vector systems may be problematic in that they may elicit immunogenic and cytotoxic responses and the transgene needs to be turned off after a certain time [12]. Extensive scarring may be induced by the chronic placement of intrathecal tubing, thereby augmenting cord tissue damage [13]. Because these varying growth factor delivery approaches have limitations for human SCI repair, we sought to devise a non-cytotoxic gelatin scaffold material in the form of a tube or membrane as an alternative delivery system for local and sustained drug release of neurotrophins.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of growth factor- and extracellular matrix-loaded, gelatin-based scaffolds and their biocompatibility with Schwann cells and dorsal root ganglia

Sazo

Maenaka

et al. 2012

Biomaterials

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One of the most exciting new avenues of research to repair the injured spinal cord is to combine cells for implantation with scaffolds that protect the cells and release growth factors to improve their survival and promote host axonal regeneration. To realize this goal, we fabricated biodegradable, photocurable gelatin tubes and membranes for exploratory in vitro studies. Detailed methods are described for their fabrication with a high gelatin concentration. Gelatin membranes fabricated in the same way as tubes and photo-co-immobilized with rhBDNF or rhNT-3, with or without Schwann cells (SCs), showed an initial burst of neurotrophin release within 24h, with release diminishing progressively for 21 days thereafter. SCs attained their typical bipolar conformation on membranes without neurotrophins but adhesion, alignment and proliferation were improved with neurotrophins, particularly rhBDNF. When dorsal root ganglion explants were cultured on membranes containing laminin and fibronectin plus both neurotrophins, neurite outgrowth was lengthier compared to combining one neurotrophin with laminin and fibronectin. Thus, these gelatin membranes allow SC survival and effectively release growth factors and harbor extracellular matrix components to improve cell survival and neurite growth. These scaffolds, based on the combination of cross-linked gelatin technology and incorporation of neurotrophins and extracellular matrix components, are promising candidates for spinal cord repair.

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Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury

Cited by 9 publications

References 26 publications

An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

Neural stem cell transplantation combined with erythropoietin for the treatment of spinal cord injury in rats

Fabrication of growth factor- and extracellular matrix-loaded, gelatin-based scaffolds and their biocompatibility with Schwann cells and dorsal root ganglia

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