Adeno‐associated virus‐mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord–contused rats

Huang, Wen Cheng; Kuo, Huai Sheng; Tsai, Ming-Tzu; Ma, Hsu; Chiu, Chuan Wen; Huang, Ming Chao; Yang, Lin; Chang, Pei Teh; Lin, Yi Lo; Kuo, Wen Chun; Lee, Meng Jen; Liu, Jiang Chuan; Cheng, Henrich

doi:10.1002/jgm.1568

Cited by 23 publications

(10 citation statements)

References 50 publications

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“…SCI was induced in adult female SD rats using the New York University weight-drop device as described previously [29,31]. Animal handling and experimental protocols were carefully reviewed and approved by the animal studies subcommittee of Taipei Veterans Hospital (IACUC 2015-167 and IACUC 2016-291).…”

Section: Methodsmentioning

confidence: 99%

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

Tsai

Liou

Lin

et al. 2018

JCM

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Spinal cord injury (SCI) is a devastating neurological condition and might even result in death. However, current treatments are not sufficient to repair such damage. Bone marrow mesenchymal stem cells (BM-MSC) are ideal transplantable cells which have been shown to modulate the injury cascade of SCI mostly through paracrine effects. The present study investigates whether systemic administration of conditioned medium from MSCs (MSCcm) has the potential to be efficacious as an alternative to cell-based therapy for SCI. In neuron-glial cultures, MSC coculture effectively promoted neuronal connection and reduced oxygen glucose deprivation-induced cell damage. The protection was elicited even if neuron-glial culture was used to expose MSCcm, suggesting the effects possibly from released fractions of MSC. In vivo, intravenous administration of MSCcm to SCI rats significantly improved behavioral recovery from spinal cord injury, and there were increased densities of axons in the lesion site of MSCcm-treated rats compared to SCI rats. At early days postinjury, MSCcm treatment upregulated the protein levels of Olig 2 and HSP70 and also increased autophage-related proteins in the injured spinal cords. Together, these findings suggest that MSCcm treatment promotes spinal cord repair and functional recovery, possibly via activation of autophagy and enhancement of survival-related proteins.

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Section: Methodsmentioning

confidence: 99%

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

Tsai

Liou

Lin

et al. 2018

JCM

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“…The role of FGF1 in neurogenesis, neurite outgrowth, and neuronal maturation and differentiation is well described (Turner et al, 2006;Hsu et al, 2013). FGF1 has been shown to act as a neurotrophic, neuroprotective, and angiogenic factor during development and repair process following brain or spinal cord injury (Hossain et al, 2002;Dono, 2003;Cheng et al, 2011;Huang et al, 2011;Tsai et al, 2015). Local administration of FGF1 caused significant functional improvements in obstetric brachial plexus palsy and chronic transverse myelitis (Lin et al, 2005(Lin et al, , 2006.…”

Section: Figmentioning

confidence: 99%

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

Hoseini

Ghazavi

Forouzanfar

et al. 2017

DNA and Cell Biology

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The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCs), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCs was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSC-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCs efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCs may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.

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“…In 1996, Cheng et al led a study and concluded that adult rats with SCI could have partial recovery of hindlimb function after nerve transfer and acidic fibroblast growth factor (aFGF) [ 6 ]. His study group in Taiwan then performed several studies to support the promising therapy [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. This therapy may be one of the multi-modality treatments for SCI.…”

Section: Introductionmentioning

confidence: 99%

The Application of an Omentum Graft or Flap in Spinal Cord Injury

Fay

Lin

Liou

et al. 2021

IJMS

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Background: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration. Methods: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord. Results: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, p < 0.05). Furthermore, the reduction in cavity and the preservation of class III β-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers (p < 0.05) and a reduced injured cavity, though locomotor scores were similar. Conclusions: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.

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Adeno‐associated virus‐mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord–contused rats

Abstract: These data suggest that supplement of aFGF improve the functional recovery of spinal cord-contused rats and that AAV-aFGF-mediated gene transfer could be a clinically feasible therapeutic approach for patients after nervous system injuries.

Cited by 23 publications

References 50 publications

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

Attenuating Spinal Cord Injury by Conditioned Medium from Bone Marrow Mesenchymal Stem Cells

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

The Application of an Omentum Graft or Flap in Spinal Cord Injury

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