Transplanted Neural Stem Cells Survive, Differentiate, and Improve Neurological Motor Function after Experimental Traumatic Brain Injury

Rieß, Peter; Zhang, Chen; Saatman, Kathryn E.; Laurer, Helmut; Longhi, Luca; Raghupathi, Ramesh; Lenzlinger, Philipp M.; Lifshitz, Jonathan; Boockvar, John A.; Neugebauer, Edmund; Snyder, Evan Y.; McIntosh, Tracy K.

doi:10.1097/00006123-200210000-00035

Cited by 138 publications

(100 citation statements)

References 46 publications

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“…We also tested different post-injury time points for transplantation, and found that grafting at 2 days post-injury had better cell survival compared to transplantation at 7 or 14 days post-injury (data not included). The results are similar to some from previously reported studies using other cell sources (Boockvar et al, 2005;Riess et al, 2002). Using the stereological cell quantification method, we determined the remaining number of transplanted cells at 2 and 4 weeks following transplantation, and found around 46% of total injected cells and 36% in the injured brain, respectively, and 48% and 39% in the sham brain, respectively.…”

Section: Discussionsupporting

confidence: 88%

“…However, what is unclear is which of these environments is more conducive for cell transplant survival. Within a different post-injury environment, published studies using cell sources ranging from embryonic murine (Boockvar et al, 2005;Hoane et al, 2004;Philips et al, 2001;Riess et al, 2002;Wallenquist et al, 2009), or fetal stem cell lines (Hagan et al, 2003;Shear et al, 2004;Tate et al, 2002Tate et al, , 2009Wennersten et al, 2004), to bone marrow cells (Mahmood et al, 2001a(Mahmood et al, , 2001b(Mahmood et al, , 2003Qu et al, 2009), have reported varying degrees of cell survival after transplantation into the injured brain, both at early and later post-injury time points. Many studies have indicated that post-injury timing and location of implantation are important factors determining the fate of transplanted NS/NPCs.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that transplantation of NS/ NPCs derived from fetal or bone marrow can improve functional recovery following experimental brain injury (Gao et al, 2006;Mahmood et al, 2001b;Riess et al, 2002;Sinson et al, 1996). In the current study, we examined cognitive function in experimental subjects.…”

Section: Sun Et Almentioning

confidence: 97%

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Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

Sun

Gugliotta

Rolfe

et al. 2011

Journal of Neurotrauma

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Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

Sun

Gugliotta

Rolfe

et al. 2011

Journal of Neurotrauma

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“…Similar results were observed with fetal-derived NSCs overexpressing EGF receptor, when transplanted to the corpus callosum of CCI animals 49. These cells became mature neurons following transplantation into animals that showed significantly improved motor function, although cognitive dysfunction was unaffected 50. Alternately, improved cognition was observed when transplanted cells had been transduced with glial cell derived neurotrophic factor (GDNF), which showed an increased migration from the injury periphery 51.…”

Section: Tbi and Stem Cell Transplantationsupporting

confidence: 58%

Stem cells for therapy in TBI

et al. 2015

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While the pace of traumatic brain injury (TBI) research has accelerated, the treatment options remain limited. Clinical trials are yet to yield successful treatment options, leading to innovative strategies to overcome the severe debilitating consequences of TBI. Stem cells may act as a potential treatment option. They have two key characteristics, the ability of self-renewal and the ability to give rise to daughter cells, which in the case of neural stem cells (NSCs) includes neurons, astrocytes and oligodendrocytes. They respond to the injury environment providing trophic support and have been shown to differentiate and integrate into the host brain. In this review, we introduce the notion of an NSC and describe the two neurogenic niches in the mammalian brain. The literature supporting the activation of an NSC in rodent models of TBI, both in vivo and in vitro, is detailed. This endogenous activation of NSCs may be augmented by exogenous transplantation of NSCs. Delivery of NSCs to assist the host nervous system has become an attractive option, with either fetal or adult NSC. This has resulted in cognitive and functional improvement in rodents, and current animal studies are using human NSCs. While no NSC clinical trials are currently ongoing for TBI, this review touches upon other neurological diseases and discuss how this may move forward into TBI.

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“…However, stem cell therapies have offered some promise. Studies have shown that transplantation of neural stem cells provides neuroprotection after TBI (Riess et al 2002; Bakhtiary et al 2011; Arien-Zakay et al 2012; Wang et al 2013). Primarily through paracrine and endocrine mechanisms (Camussi et al 2010), stem cells regulate inflammatory response, decrease free radical production, reduce apoptosis, and promote endogenous neuronal growth, synaptic connections, and neural repair (Joyce et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Wharton’s Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury

Tian

Yang

et al. 2015

Cell Mol Neurobiol

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Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21 to 28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI.

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Transplanted Neural Stem Cells Survive, Differentiate, and Improve Neurological Motor Function after Experimental Traumatic Brain Injury

Abstract: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.

Cited by 138 publications

References 46 publications

Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

Stem cells for therapy in TBI

Wharton’s Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury

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