Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats

Chung, HY; Chung, Wook-Hun; Lee, Jae‐Hoon; Chung, Dai-Jung; Yang, Wojong; Lee, A-Jin; Choi, Chi-Bong; Chang, Hwa-Seok; Kim, Dae-Hyun; Suh, Hyun Jung; Lee, Dong Hun; Hwang, Sung Ho; Hee, Sun; Kim, Hwi-Yool

doi:10.4142/jvs.2016.17.1.97

Cited by 26 publications

(26 citation statements)

References 36 publications

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“…Regarding the mechanisms underlying PA, we demonstrated that A91 immunization induces a specific anti-A91 response that is capable of producing—in vitro—brain derived neurotrophic factor (BDNF), a molecule that induces axonal regeneration and confers motor function improvement after SC-injury. Some studies have also shown that BDNF and another neurotrophic factor, NT-3, prevent neuronal apoptosis [ 26 , 27 ] and promote axonal sprouting and regeneration [ 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury

et al. 2016

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Background After spinal cord (SC)-injury, a non-modulated immune response contributes to the damage of neural tissue. Protective autoimmunity (PA) is a T cell mediated, neuroprotective response induced after SC-injury. Immunization with neural-derived peptides (INDP), such as A91, has shown to promote—in vitro—the production of neurotrophic factors. However, the production of these molecules has not been studied at the site of injury.ResultsIn order to evaluate these issues, we performed four experiments in adult female Sprague–Dawley rats. In the first one, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) concentrations were evaluated at the site of lesion 21 days after SC-injury. BDNF and NT-3 were significantly increased in INDP-treated animals. In the second experiment, proliferation of anti-A91 T cells was assessed at chronic stages of injury. In this case, we found a significant proliferation of these cells in animals subjected to SC-injury + INDP. In the third experiment, we explored the amount of BDNF and NT3 at the site of injury in the chronic phase of rats subjected to either SC-contusion (SCC; moderate or severe) or SC-transection (SCT; complete or incomplete). The animals were treated with INDP immediately after injury. Rats subjected to moderate contusion or incomplete SCT showed significantly higher levels of BDNF and NT-3 as compared to PBS-immunized ones. In rats with severe SCC and complete SCT, BDNF and NT-3 concentrations were barely detected. Finally, in the fourth experiment we assessed motor function recovery in INDP-treated rats with moderate SC-injury. Rats immunized with A91 showed a significantly higher motor recovery from the first week and up to 4 months after SC-injury.ConclusionsThe results of this study suggest that PA boosted by immunization with A91 after moderate SC-injury can exert its benefits even at chronic stages, as shown by long-term production of BDNF and NT-3 and a substantial improvement in motor recovery.

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Section: Discussionmentioning

confidence: 99%

Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury

et al. 2016

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“…In terms of the selection of UCB-MNCs, the aim is to improve recovery after chronic SCI. Several mechanisms have been proposed for the UCB-MNCs to improve recovery after CNS injury, involving secretion of anti-inflammatory cytokines [ 24 , 25 , 26 ], growth factors release [ 27 , 28 , 29 ], matrix metalloproteinase upregulation [ 25 ], tissue plasminogen activator downregulation [ 26 ], apoptosis prevention [ 24 ], mediation in myelination process [ 30 , 31 ], decreased gliosis [ 32 ], and increased angiogenesis [ 33 ].…”

Section: Cell Therapiesmentioning

confidence: 99%

Translational Regenerative Therapies for Chronic Spinal Cord Injury

Dalamagkas

Tsintou

Seifalian

et al. 2018

IJMS

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Spinal cord injury is a chronic and debilitating neurological condition that is currently being managed symptomatically with no real therapeutic strategies available. Even though there is no consensus on the best time to start interventions, the chronic phase is definitely the most stable target in order to determine whether a therapy can effectively restore neurological function. The advancements of nanoscience and stem cell technology, combined with the powerful, novel neuroimaging modalities that have arisen can now accelerate the path of promising novel therapeutic strategies from bench to bedside. Several types of stem cells have reached up to clinical trials phase II, including adult neural stem cells, human spinal cord stem cells, olfactory ensheathing cells, autologous Schwann cells, umbilical cord blood-derived mononuclear cells, adult mesenchymal cells, and autologous bone-marrow-derived stem cells. There also have been combinations of different molecular therapies; these have been either alone or combined with supportive scaffolds with nanostructures to facilitate favorable cell–material interactions. The results already show promise but it will take some coordinated actions in order to develop a proper step-by-step approach to solve impactful problems with neural repair.

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ nerve growth factor (NGF) in the injured spinal cord is the main therapeutic mechanism of this effect 14 . Most studies of stem cell therapy in SCI have focused on motor limb functions and sensory recovery.…”

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confidence: 99%

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

Liang

Shaw

et al. 2020

Sci Rep

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The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-β1, and β3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-β1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-β1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and β3-adrenoceptor expression. Spinal cord injury (SCI) affects approximately 2.5 million people worldwide and may cause severe physical disabilities 1. Most patients with SCI develop neurogenic bladder symptoms, including overactive bladder, urinary retention, urinary tract infection, and chronic renal failure 2,3. These neurogenic bladder conditions cause altered tissue morphology, such as bladder hypertrophy 4 and fibrosis 5 , which adversely affect detrusor muscle function and result in bladder of low compliance and capacity 6. Although the effects of SCI on bladder function have been extensively studied, changes in the mechanical behaviour of the SCI bladder wall tissue have not been fully established. Abnormal expression of collagen and elastin in human bladder muscle is a histological feature characteristic of noncompliant bladder 5,7. In animal studies, bladder wall compliance is closely related to the collagen and elastin content 8,9. In addition, insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-β1) were reported to be involved in tissue remodelling and bladder wall fibrosis after SCI 9-11. Patients with chronic SCI and neurogenic bladder symptoms are currently treated with antimuscarinic medications, β3-adrenoceptor agonists, and bladder catheterization. However, these therapeutic methods are not effective and associated with adverse effects, such as dry mouth and constipation 12. Recent research efforts have focused on attempts to regenerate the injured spinal cord using cell transplantation 13. A previous study showed that the treatment of SCI with umbilical cord blood stem cells could...

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Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats

Cited by 26 publications

References 36 publications

Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury

Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury

Translational Regenerative Therapies for Chronic Spinal Cord Injury

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

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