Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage

Chiba, Shunmei; Ikeda, Ritsuko; Kurokawa, Manae S.; Yoshikawa, Hideshi; Takeno, Mitsuhiro; Nagafuchi, Hiroko; Tadokoro, Mamoru; Sekino, Hiroaki; Hashimoto, Tsuyoshi; Suzuki, Noboru

doi:10.1016/j.jns.2004.01.006

Cited by 42 publications

(36 citation statements)

References 52 publications

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“…At 13 weeks NSCs transplanted ipsilaterally showed neuronal (NeuN) and astrocytic (GFAP) markers whereas contralaterally transplanted NSC′s only expressed neuronal markers [24]. Studies pre-differentiating ES cells, using all-trans retinoic acid (RA) to induce differentiation into neuron-like cells in vitro, have shown cell survivability [7,13], significantly improved motor [7] and sensorimotor function [13]. These grafted cells have also been shown to contain synaptic vesicles, which suggests that the have functional capability [7].…”

Section: Discussionmentioning

confidence: 99%

“…Studies pre-differentiating ES cells, using all-trans retinoic acid (RA) to induce differentiation into neuron-like cells in vitro, have shown cell survivability [7,13], significantly improved motor [7] and sensorimotor function [13]. These grafted cells have also been shown to contain synaptic vesicles, which suggests that the have functional capability [7]. A recent study has shown that pre-differentiated ES cells transplanted following excitotoxic SCI act in a neuroprotective manner and provide antinociceptive and therapeutic effects [10].…”

Section: Discussionmentioning

confidence: 99%

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Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Becerra

Tatko

Pak

et al. 2007

Behavioural Brain Research

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Embryonic stem (ES) cells have been investigated in many animal models of injury and disease. However, few studies have examined the ability of pre-differentiated ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to compare the effect of murine ES cells that were pre-differentiated into GABAergic neurons or astrocytes on functional recovery following TBI. Neural and astrocyte induction was achieved by co-culturing ES cells on a bone marrow stromal fibroblast (M2-10B4) feeder layer and incubating them with various mitogenic factors. Rats were initially prepared with a unilateral controlled cortical contusion injury of the sensorimotor cortex or sham procedure. Rats were transplanted 7 days following injury with ∼100K GABAergic neurons, astrocytes, fibroblasts, or media. Animals were assessed on a battery of sensorimotor tasks following transplantation. The stromal fibroblast cells (M2-10B4), as a control cell line, did not differ significantly from media infusions. Transplantation of GABAergic neurons facilitated complete and total recovery on the vibrissae-forelimb placing test as opposed to all other groups, which failed to show any recovery. It was also found that GABAergic neurons reduced the magnitude of the initial impairment on the limb use test. Histological analysis revealed infiltration of host brain with transplanted neurons and astrocytes. The results of the present study suggest that transplantation of pre-differentiated GABAergic neurons significantly induces recovery of sensorimotor function; whereas, astrocytes do not.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Becerra

Tatko

Pak

et al. 2007

Behavioural Brain Research

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“…A spatiotemporal evolution of core and penumbra was also seen 6 ; at earlier time points the histological infarct core, as measured by TTC is in the striatum, and the viable tissue was around this core, and included the cortex. Subsequently the TTC- Further study may prove that, in addition to ischemic stroke, the strategy is applicable to cell therapies for other CNS and non-CNS disorders.…”

Section: Discussionmentioning

confidence: 85%

Transplantation of mouse embryonic stem cell after middle cerebral artery occlusion

Lee

2012

Acta Cir. Bras.

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PURPOSE: Stem cell transplantation has been extensively studied as individual therapies for ischemic stroke. The present investigation is an initial effort to combine these methods to achieve increased therapeutic effects after brain ischemia. Cell transplantation may recover massive neuronal loss by replacing damaged brain cells. METHODS: Undifferentiated mouse embryonic stem (mES) cells were used to induce differentiation in vitro into neuron-like cells with good cell viability for use a graft. In this study, middle cerebral artery occlusion (MCAO) was induced in rats using intra-luminal vascular occlusion, and infused mES cells after MCAO. The animals were examined behaviorally using motor and sensory test with neurological assessment. RESULTS: Motor function of the recipients was gradually improved, whereas little improvement was observed in control rats. This result may suggest that the grafted cells have synaptic connection in the recipient brain. Our study revealed that stem cell transplantation can have a positive effect on behavioral recovery and reduction of infarct size in focal ischemic rats. Consequently after euthanasia, rats were histochemically investigated to explore graft survival with green fluorescent protein (GFP). CONCLUSION: The mouse embryonic stem cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction.

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“…Immunofluorescence staining was conducted as reported previously [16][17][18] . In brief, for all immunofluorescence procedures, cultured cells were fixed in 4 % paraformaldehyde for 15 minutes.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

Sonic Hedgehog Supplementation Rapidly induces Myogenesis in Human Induced Pluripotent Stem Cells

Shiratsuchi

Misawa

Saito

et al. 2015

J St. Marianna Univ

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We have reported that mouse embryonic stem (ES) cells transfected with insulin-like growth factor (IGF) II differentiated into mature skeletal muscle cells in vitro and in vivo after transplantation. On the contrary, IGFII transfected human induced pluripotent stem (hiPS) cells did not demonstrate mature skeletal muscle differentiation. The morphogenic factor Sonic Hedgehog (SHH) was suggested to upregulate the myogenic process along with IGF through Phosphoinositide 3 kinase (PI3K)/Akt signaling pathway. We cultured hiPS cells with SHH to generate myoblasts and transplanted the cells to hind limbs of mice.SHH with IGFII supplementation rapidly enhanced myogenic gene and protein expressions (MyoD, myogenin, Mrf4, and dystrophin) of hiPS cells. After the transplantation, we observed severe inflammation in the transplanted sites with host immunocompetent cells despite systemic administration of dexamethasone and cyclosporine. Surviving transplanted myoblasts showed lower expressions of myogenic proteins (MyoD, myogenin, and dystrophin) than in vitro cultured myoblasts did.We successfully generated mature skeletal muscle cells from hiPS cells with SHH supplementation. We suggest that further studies are needed to characterize the underlying molecular mechanisms of transplanted myoblasts derived from hiPS cells for the formation of mature human skeletal muscle.

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Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage

Cited by 42 publications

References 52 publications

Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Transplantation of mouse embryonic stem cell after middle cerebral artery occlusion

Sonic Hedgehog Supplementation Rapidly induces Myogenesis in Human Induced Pluripotent Stem Cells

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