Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia

Kurimoto, Yasuo; Shibuki, Hiroto; Kaneko, Yoshiaki; Ichikawa, Masaki; Kurokawa, Toru; Takahashi, Masayo; Yoshimura, Nagahisa

doi:10.1016/s0304-3940(01)01857-2

Cited by 87 publications

(53 citation statements)

References 12 publications

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“…Some of the transplanted NSCs integrate into inappropriate retinal layers with the age of the host having an important role in determining NSC fate [40][41][42], whereas other NSCs do not integrate but survive in the subretinal space with limited expression of retinal cell phenotypes [40]. As with RPCs, integration increases when NSCs are transplanted into young or injured host retina [43,44], and at the other extreme, NSCs transplanted into healthy adult monkey show little migration or integration, forming a monolayer of stable NSCs [45]. Integration may not be necessary to rescue photoreceptor cell loss; however, NSCs derived from committed CNS tissue rescue photoreceptor cells in animal models of retinal disease presumably by release of growth factors and/or phagocytosis of photoreceptor cell outer segments shed during the early steps of vision [46,47].…”

Section: Neural Stem Cellsmentioning

confidence: 99%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

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Section: Neural Stem Cellsmentioning

confidence: 99%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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“…In order to study whether certain pathological conditions could improve graft integration and promote retinal specific neuron differentiation of transplanted brainderived neural progenitor cells, investigators performed transplants in normal rats following ischemic or mechanical injury, and in retinal degenerate rats (Chacko et al, 2003;Guo et al, 2003;Kurimoto et al, 2001;Mizumoto et al, 2003;Nishida et al, 2000;Young et al, 2000). However, in all of these studies, despite morphological similarities to various retinal cell types and extensive incorporation within the host retina, the transplanted hippocampus-derived cells failed to differentiate into retinal-specific lineages.…”

Section: Introductionmentioning

confidence: 99%

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Qiu

Seiler

Mui

et al. 2005

Experimental Eye Research

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Previous studies evaluating neural stem cells transplanted into the mature retina have demonstrated limited levels of graft-host integration and photoreceptor differentiation. The purpose of this investigation is to enhance photoreceptor cell differentiation and integration of retinal progenitor cells (RPC) following subretinal transplantation into retinal degenerate rats by optimization of isolation, expansion, and transplantation procedures.RPCs were isolated from human placental alkaline phosphatase (hPAP)-positive embryonic day 17 (E17) rat retina and expanded in serum-free defined media. RPCs at passage 2 underwent in vitro induction with all trans retinoic acid or were transplanted into the subretinal space of post-natal day (P) 17 S334ter-3 and S334ter-5 transgenic rats. Animals were examined post-operatively by ophthalmoscopy and optical coherence tomography (OCT) at weeks 1 and 4. Differentiation profiles of RPCs, both in vitro and in vivo were analysed microscopically by immunohistochemistry for various retinal cell specific markers. Our results demonstrated that the majority of passage 2 RPCs differentiated into retina-specific neurons expressing rhodopsin after in vitro induction. Following subretinal transplantation, grafted cells formed a multi-layer cellular sheet in the subretinal space in both S334ter-3 and S334ter-5 rats. Prominent retina-specific neuronal differentiation was observed in both rat lines as evidenced by recoverin or rhodopsin staining in 80% of grafted cells. Less than 5% of the grafted cells expressed glial fibrillary acidic protein. Synapsin-1 (label for nerve terminals) positive neural processes were present at the graft-host interface. Expression profiles of the grafted RPCs were similar to those of RPCs induced to differentiate in vitro using all-trans retinoic acid.In contrast to our previous study, grafted RPCs can demonstrate extensive rhodopsin expression, organize into layers, and show some features of apparent integration with the host retina following subretinal transplantation in slow and fast retinal degenerate rats. The similarity of the in vitro and in vivo RPC differentiation profiles suggests that intrinsic signals may have a significant contribution to RPC cell fate determination. q

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“…Indeed, transplantation of various neural precursor cells into the retina has been carried out in the normal neonatal and adult host retina (Seigel et al, 1998;Takahashi et al, 1998;Chacko et al, 2000;Warfvinge et al, 2001;Blixt Wojciechowski et al, 2002a, 2004van Hoffelen et al, 2003), degenerating retina (Young et al, 2000;Mizumoto et al, 2001;Pressmar et al, 2001;Blixt Wojciechowski et al, 2002b;Yang et al, 2002), as well as in injured retina (Nishida et al, 2000;Kurimoto et al, 2001;Shatos et al, 2001); however, with varying results in terms of integration, migration, and differentiation. At present, it is recognized that grafted neural precursor cells may provide dual functions in a diseased retina: replace lost cells or serve as vehicles for gene delivery of therapeutic substances.…”

Section: Introductionmentioning

confidence: 99%

Migratory capacity of the cell line RN33B and the host glial cell response after subretinal transplantation to normal adult rats

Wojciechowski

Englund

Lundberg

et al. 2004

Glia

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As previously reported, the brain-derived precursor cell line RN33B has a great capacity to migrate when transplanted to adult brain or retina. This cell line is immortalized with the SV40 large T-antigen and carries the reporter gene LacZ and the green fluorescent protein GFP. In the present study, the precursor cells were transplanted to the subretinal space of adult rats and investigated early after grafting. The purpose was to demonstrate the migration of the grafted cells from the subretinal space into the retina and the glial cell response of the host retina. Detachment caused by the transplantation method was persistent up to 4 days after transplantation, and then reattachment occurred. The grafted cells were shown to migrate in between the photoreceptor cells before entering into the plexiform layers. Molecules involved in migration of immature neuronal cells as the polysialylated neural cell adhesion molecule (PSA-NCAM) and the collapsing response-mediated protein 4 (TUC-4) was found in the plexiform layers of the host retina, but not in the grafted cells. The expression of the intermediate filaments GFAP, vimentin, and nestin was intensely upregulated immediately after transplantation. A less pronounced upregulation was observed on sham-operated animals. In summary, the RN33B cell line migrated promptly posttransplantation and settled preferably into the plexiform layers of the retina, the same layers where the migration cues PSA-NCAM and TUC-4 were established. In addition, both the transplantation method per se and the implanted cells caused an intense glial cell response by the host retina.

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Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia

Cited by 87 publications

References 12 publications

Stem Cells for Retinal Replacement Therapy

Stem Cells for Retinal Replacement Therapy

Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats

Migratory capacity of the cell line RN33B and the host glial cell response after subretinal transplantation to normal adult rats

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