Human ciliary neurotrophic factor–overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury

Abbaszadeh, Hojjat-Allah; Tiraihi, Taki; Noori-Zadeh, Ali; Delshad, Ali; Majid, Shahana; Taheri, Taher

doi:10.1016/j.jcyt.2015.03.689

Cited by 28 publications

(27 citation statements)

References 21 publications

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“…Increasing evidence suggests that NTFs can alter the balance between neurite re-growth-inhibiting and -inducing molecules. As a result, these NTFs, particularly CNTF, can promote cell survival and axonal re-growth over neurodegeneration (Müller et al, 2009; Abbaszadeh et al, 2015). In addition, CNTF has been speculated to improve the efficacy of cell transplantation, highlighting the important role CNTF plays during BMSC transplantation in the rat SCI model (Abbaszadeh et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms underlying the ability of BMSCs to promote functional remodeling after SCI are likely related to the anti-proliferative and anti-apoptotic proprieties of these cells, which exert anti-inflammatory and immunosuppressive effects at the injury site; additionally, BMSCs induce the repair of nerve cells, promote axonal regeneration, and restore nerve trophism by secreting NTFs (Ohta et al, 2004; Neuhuber et al, 2005; Abrams et al, 2009; Sakata et al, 2011; Tran et al, 2011; Uccelli et al, 2011; Xia et al, 2014; Abbaszadeh et al, 2015; Han et al, 2015). These effects translate into functional improvement, as a study using a dog model of SCI demonstrated that both autologous and allogenic BMSC transplantation improved neurological function following SCI and noted that these improvements were associated with reduced interleukin-6 (IL-6) and cyclooxygenase-2 levels (Jung et al, 2009; Ryu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

Xiong

Liu

et al. 2017

Front. Cell. Neurosci.

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Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs) both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β) density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3) and ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals’ Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3 signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

Xiong

Liu

et al. 2017

Front. Cell. Neurosci.

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“…They participate in neurogenesis, neuronal survival, axonal growth, synaptogenesis, and activity-dependent forms of synaptic plasticity [63][64][65][66]. Neuron survival and the regeneration of fiber tracts is aided by neurotrophic factors, including, neurotrophin-3 (NT-3) [67], neurotrophin-4/5 (NT-4/5) [68], brain-derived neurotrophic factor (BDNF) [69], glial cell linederived neurotrophic factor (GDNF) [70], and ciliary neurotrophic factor (CNTF) [71]. BDNF promotes the survival of existing neurons as well as the growth and differentiation of new neurons and synapses.…”

Section: Neurotrophic Factorsmentioning

confidence: 99%

Holistic Approach to Axonal Regeneration in Cases of Spinal Cord Injury

Yeh¹

2018

J Biomol Res Ther

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“…Acute CNTF delivery following contusion SCI using transfected rat MPCs from bone marrow improved axonal regrowth and functional recovery (Abbaszadeh et al, 2015). It remains unresolved whether MPCs (or any donor cell type for that matter) can simply improve the terrain of the injury site to enhance existing endogenous repair processes and promote functional and morphological outcomes after SCI as a result.…”

Section: Neuropoietic Cytokinesmentioning

confidence: 99%