Migration, integration, and differentiation of hippocampus-derived neurosphere cells after transplantation into injured rat spinal cord

Wu, Sufan; Suzuki, Yoshihisa; Kitada, Masaaki; Kitaura, Miyako; Kataoka, K.; Takahashi, J.; Idé, Chizuka; Nishimura, Yoshihiko

doi:10.1016/s0304-3940(01)02219-4

Cited by 94 publications

(69 citation statements)

References 14 publications

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“…44 Fetal transplants have also been implanted into the injured rat spinal cord where they migrate and differentiate. 45 However, these CNS grafts are site specific which is a limiting factor.…”

Section: The Autonomic Motor Systemmentioning

confidence: 99%

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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The first step essential in the search for a cure of human spinal cord injury (SCI) is to appreciate the complexity of the disorder. In this regard, it is not only the loss of ambulation but the sensory and autonomic changes that are equally important in recovery. In addition, there are the serious social emotional psychological and lifestyle effects of SCI which should also be taken into account. It is also true that no two SCI lesions are alike as each is the result of a SCI unique to that individual. Clinically of utmost importance is the segmental level of injury and whether it is complete, incomplete or discomplete (loss of all neurological functions below the injury but with physiological or anatomical continuity of Central nervous system tracts across the lesion). We are not concerned here with primary and secondary prevention or methods designed to limit the severity of the lesion after the event, important as they are, but with the requirements for a cure. Clearly, the greater the number of nerve fibers that can be preserved in the acute stage, the better will be the end result. Our focus at present is on the end-stage lesion with the aim of showing that a cure for SCI will depend upon establishing functionally useful central axonal regeneration and reestablishing physiological reconnections. Existing experimental methods are based on stimulating axonal regeneration by neutralizing inhibitory factors, adding positive trophisms and creating a permissive environment. Better results are obtained by bridging the gap with grafts of peripheral nerves or transplants of Schwann cells and genetically engineered fibroblasts. Recently, the potential for stem cells to enhance this process has created great interest. This is because of the ability of pluripotential cells to differentiate into neural tissue. A cure based on the physiopathology of SCI requires pyramidal, extrapyramidal, sensory, cerebellar and autonomic pathways to be regenerated with their appropriate neurotransmitters restored and reflexes integrated physiologically and in synchrony. In human SCI, there is a very long distance anatomically for axonal regrowth to occur in order to reach their relevant nuclei. This is because of continuing Wallerian degeneration. It also presumes that the target neurons are intact and that there has been no transneuronal degeneration above or below the lesion. Alternatively, in place of regenerated long axons, a multisynaptic pathway may be constructed from stem cells that have developed into neurons. Whether such a pathway would restore useful neurological functions is unknown. At present, the transplant and grafting research teams are exploring these possibilities in experimental animals. Moderate success in gaining axonal regeneration has been reported; however, it must be appreciated that the human lesion differs considerably from that of the experimental animal. In order to be successful, the neuropathology and neurophysiology of human SCI must be taken into account. The purpose of this review is to place the req...

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Section: The Autonomic Motor Systemmentioning

confidence: 99%

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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“…Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells. Neuronal stem cells are able to differentiate into astrocytes, neurons, and oligodendrocytes [3,10,23], when given the appropriate signals [2,7]. During the stage where the brain develops, gap junctional intercellular communication (GJIC) allows the diffusional exchange of ions and metabolites for communication between neighboring cells [8,14,20].…”

mentioning

confidence: 99%

Role of Gap Junctional Intercellular Communication (GJIC) through p38 and ERK1/2 Pathway in the Differentiation of Rat Neuronal Stem Cells

Yang

Cho

Ahn

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-Ø-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells. Neuronal stem cells are able to differentiate into astrocytes, neurons, and oligodendrocytes [3,10,23], when given the appropriate signals [2,7]. During the stage where the brain develops, gap junctional intercellular communication (GJIC) allows the diffusional exchange of ions and metabolites for communication between neighboring cells [8,14,20]. Connexin 32 and 43 were expressed in the neurons of adult rat or mouse [15,17], and Cx43 was the most abundant gap junction protein in the CNS [4,5]. However, no study has yet been performed to the role of gap junctions in rat neuronal stem cell differentiation. In the present study, we have examined protein expression of Cx43 and Cx32 during the neuronal stem cell differentiation and induction of Cx43 and Cx32. This can be elicited in neuronal stem cell-derived cells by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) and this induction showed that it can be prevented by the p38 MAP-Kinase inhibitor SB203580 and the MEK inhibitor PD98059. MATERIALS AND METHODSCell culture: Neuronal stem cells were prepared by culturing cells from cerebrum of embryonic day 17 (E17) Sprague-Dawley rat (Bio Genomics, Korea) fetus. Briefly, fresh cerebrums were dissociated in the presence of trypsin and DNase I and planted on a Petri dish (Nunc, IL). Cells were seeded at a density of 1~5 × 10 6 cells/ml in a mixture (1:1) of Dulbecco's modified Eagle's medium/Ham's F12 (DMEM/F12; Gibco) replenished with 2% B27 (Gibco), gentamycin (50 µg/ml), anti-PPLO (pleuro-pneumonia-like organism) reagent (100 µg/ml), recombinant human basic fibroblast growth factor (bFGF 20 ng/ml, Sigma), and epidermal growth factor (10 ng/ml).Scrape loading/ dye transfer (SL/DT) assay: Cells were treated with TPA for 1 hr. The GJIC assay was conducted at non-cytotoxic dose levels of the samples, as determined by the MTT assay. Following incubation, the cells were washed twice with 2 ml of PBS, Lucifer yellow was added to the washed cells and three scrapes were made with a surgical steel-bladed scalpel at low light intensities. These three scrapes were performed to ensure that the scrape travers...

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“…Therefore, to provide an effective recovery of the neural tissue, it is necessary to reconstruct the conditions of embryogenesis in the damaged area, in which it is possible to form not only the whole complex of different types of cells, required for restoration of the damaged neural tissue, but also the ways of their migration. To modeling such conditions, transplantation of neurospheres into the damaged area was previously used [19,20]. But, as it was shown by our experiments, the aggregates, formed by NCs isolated heterogeneous suspensions, can also be used as these structures.…”

Section: Original Articlementioning

confidence: 92%

“…In addition, alginate increases the rate of axons and erythrocytes growth in the injured spinal cord [16,17]. It has also been demonstrated that transplanted neural stem cells (NSCs), encapsulated in alginate, can survive, differentiate, integrate and migrate in the recipient spinal cord tissue [18,19].…”

Section: Disorders Of Physical Activity * Index Of Disordersmentioning

confidence: 99%

Transplantation of cryopreserved rat fetal neural cells in suspension and in multicellular aggregates into rats with spinal cord injury

Sukach¹,

Lebedinsky²,

Ochenashko³

et al. 2016

JCOT

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Today cell transplantation is one of the promising approaches of spinal cord injuries treatment. The aim of the work was to study the effect of cryopreserved fetal neural cell transplantation in suspensions and cell aggregates for motor activity recovery of rats with experimental spinal cord injury. MATERIALS AND METHODS. Cells were isolated from the brain tissue of rat fetuses 15-16 days of gestation. The formation of aggregates was performed during short-term cultivation at a concentration of 8•106 cells/mL in medium with 10 % adult rat serum. Cell transplantation was performed into the damaged area of spinal cord in aggregates or suspension. To fix transplanted cells in the damaged area we used alginate gel. RESULTS. Transplantation of cryopreserved fetal neural cells in alginate gel

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Migration, integration, and differentiation of hippocampus-derived neurosphere cells after transplantation into injured rat spinal cord

Cited by 94 publications

References 14 publications

Neuropathology: the foundation for new treatments in spinal cord injury

Neuropathology: the foundation for new treatments in spinal cord injury

Role of Gap Junctional Intercellular Communication (GJIC) through p38 and ERK1/2 Pathway in the Differentiation of Rat Neuronal Stem Cells

Transplantation of cryopreserved rat fetal neural cells in suspension and in multicellular aggregates into rats with spinal cord injury

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