Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat

Mothe, Andrea J.; Tator, Charles H.

doi:10.1016/j.neuroscience.2004.10.011

Cited by 259 publications

(139 citation statements)

References 37 publications

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“…Our results confirm and extend those of a set of previous studies indicating that the number of proliferating BrdU-labeled EC increases gradually with the time of survival after both paradigms; however, some important differences were documented and will be further clarified in the discussion (Zai and Wrathall 2005;Mothe and Tator 2005;Yamamoto et al 2001;Danilov et al 2006).…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, due to growing evidence that these cells may originate from the periventricular region along the entire ventricular axis, particularly including the forebrain SVZ (Weiss et al 1996;Coskun et al 2008), the ependymal layer of the CC has been considered as the target anatomical region in this study. Thus, we have confirmed, that majority of equally distributed BrdU-labeled nuclei occurred in the ependymal layer after SCI (Mothe and Tator 2005). Furthermore, some dividing cells migrate from the CC ependyma laterally, or dorsally towards the lesion site , most probably giving rise to macroglial elements ).…”

Section: Discussionsupporting

confidence: 79%

“…Many previous studies have documented that ependyma in the spinal cord plays a crucial role in regenerative processes after injury in lower vertebrates (Nordlander and Singer 1978), but not in adult mammals, where activated ependymal cells contribute primarly to the glial scar formation (Mothe and Tator 2005). However, under in vitro conditions, stem cells isolated from spinal ependyma give rise to functional neurons or oligodendroglia (Yamamoto et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Response of Ependymal Progenitors to Spinal Cord Injury or Enhanced Physical Activity in Adult Rat

Cizkova¹,

Nagyova²,

Slovinská³

et al. 2009

Cell Mol Neurobiol

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Ependymal cells (EC) in the spinal cord central canal (CC) are believed to be responsible for the postnatal neurogenesis following pathological or stimulatory conditions. In this study, we have analyzed the proliferation of the CC ependymal progenitors in adult rats processed to compression SCI or enhanced physical activity. To label dividing cells, a single daily injection of Bromo-deoxyuridine (BrdU) was administered over a 14-day-survival period. Systematic quantification of BrdU-positive ependymal progenitors was performed by using stereological principles of systematic, random sampling, and optical Dissector software. The number of proliferating BrdU-labeled EC increased gradually with the time of survival after both paradigms, spinal cord injury, or increased physical activity. In the spinal cord injury group, we have found 4.9-fold (4 days), 7.1-fold (7 days), 4.9-fold (10 days), and 5.6-fold (14 days) increase of proliferating EC in the rostro-caudal regions, 4 mm away from the epicenter. In the second group subjected to enhanced physical activity by running wheel, we have observed 2.1-2.6 fold increase of dividing EC in the thoracic spinal cord segments at 4 and 7 days, but no significant progression at 10-14 days. Nestin was rapidly induced in the ependymal cells of the CC by 2-4 days and expression decreased by 7-14 days post-injury. Double immunohistochemistry showed that dividing cells adjacent to CC expressed astrocytic (GFAP, S100beta) or nestin markers at 14 days. These data demonstrate that SCI or enhanced physical activity in adult rats induces an endogenous ependymal cell response leading to increased proliferation and differentiation primarily into macroglia or cells with nestin phenotype.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Response of Ependymal Progenitors to Spinal Cord Injury or Enhanced Physical Activity in Adult Rat

Cizkova¹,

Nagyova²,

Slovinská³

et al. 2009

Cell Mol Neurobiol

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“…Although several tendon-bone healing studies have been carried out with MSCs, implanted MSCs have not been tracked in previous investigations. The use of DiI, a membrane-bound fluorescent dye, is one way to track the fate of implanted cells (Mothe and Tator 2005). Previous studies have shown that DiI typically exhibits low cell toxicity and does not compromise cell viability or differentiation potential (Crawford and Braunwald 1991;Ponticiello et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing

et al. 2008

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Tendon-bone healing is important for the successful reconstruction of the anterior cruciate ligament by using the hamstring tendon. Mesenchymal stem cells (MSCs) have attracted much interest because of their self-renewing potential and multipotentiality for possible clinical use. We previously reported that MSCs derived from synovium had a higher proliferation and differentiation potential than the other MSCs that we examined. The purpose of this study was to investigate the effect and mechanism of the implantation of the synovial MSCs on tendon-bone healing in rats. Half of the Achilles' tendon grafts of rats were inserted into a bone tunnel from the tibial plateau to the tibial tuberosity with a suture-post fixation. The bone tunnel was filled with MSCs labeled with fluorescent marker DiI or without MSCs as the control. The tendon-bone interface was analyzed histologically, and collagen fibers were quantified. At 1 week, the tendon-bone interface was filled with abundant DiI-positive cells, and the proportion of collagen fiber area was significantly higher in the MSC group than in the control group. By 2 weeks, the proportion of oblique collagen fibers, which appeared to be Sharpey's fibers, was significantly higher in the MSC group than in the control group. At 4 weeks, the interface tissue disappeared, and the implanted tendon appeared to attach to the bone directly in both groups. DiI-labeled cells could no longer be observed. Implantation of synovial MSCs into bone tunnel thus accelerated early remodeling of tendon-bone healing, as shown histologically.

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“…Indeed, increasing evidence demonstrates that SCI elicits NSPCs proliferation in the ependymal region [7][8][9][10]. But inconsistent with expectation, endogenous neurogenesis and remyelination is very limited after SCI because activated NSPCs primarily differentiate into astrocytes rather than neurons or oligodendrocytes [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats

et al. 2015

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Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (β-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

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Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat

Cited by 259 publications

References 37 publications

Response of Ependymal Progenitors to Spinal Cord Injury or Enhanced Physical Activity in Adult Rat

Response of Ependymal Progenitors to Spinal Cord Injury or Enhanced Physical Activity in Adult Rat

Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats

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