Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

@article{Lund2006HumanES,
  title={Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.},
  author={Raymond D. Lund and Shaomei Wang and Irina V. Klimanskaya and Toby M. Holmes and Rebeca Ramos-Kelsey and Bin Lu and S. V. Girman and Nicholas Bischoff and Yves Sauve and Robert Lanza},
  journal={Cloning and stem cells},
  year={2006},
  volume={8 3},
  pages={
          189-99
        }
}
Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were… 
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...

References

SHOWING 1-10 OF 34 REFERENCES

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

  • R. LundP. Adamson J. Greenwood
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The efficacy of subretinal transplantation of two independent human RPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro are examined to demonstrate the potential of genetically modified human R PE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RPE dysfunction.

Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics.

A differentiation system that does not require coculture with animal cells or factors is described, thus allowing the production of zoonoses-free RPE cells suitable for subretinal transplantation in patients with retinal degenerative diseases.

Embryonic Stem Cells: Potential Source for Ocular Repair

This review focuses on reproducible and efficient differentiation methods for the generation of lens cells, retinal neurons, and retinal pigment epithelial cells from ES cells, which are expected to alleviate the problem of the shortage of donor cells for cell-replacement therapy.

Retinal Incorporation and Differentiation of Neural Precursors Derived from Human Embryonic Stem Cells

The results suggest that hESCs have the potential to differentiate into retinal cells and that the subretinal microenvironment supports their differentiation toward a photoreceptor fate.

Photoreceptor repair in response to RPE transplants in RCS rats: Outer segment regeneration

This study investigated the photoreceptor rescue effects in RCS rats within the first three weeks following transplantation in an attempt to determine if RPE transplants initiate repair mechanisms, specifically, outer segment (OS) regeneration.

Transplanted human embryonic germ cell‐derived neural stem cells replace neurons and oligodendrocytes in the forebrain of neonatal mice with excitotoxic brain damage

It is concluded that human EG cell‐derived NSCs can engraft successfully into injured newborn brain, where they can survive and disseminate into the lesioned areas, differentiate into neuronal and glial cells, and replace lost neurons.

Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of Surgeons rats.

This study demonstrates that ex vivo gene therapy and subsequent cell transplantation can be effective in preserving photoreceptors from the cell death that normally accompanies retinal degeneration.

Preservation of visual responsiveness in the superior colliculus of RCS rats after retinal pigment epithelium cell transplantation

Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell‐based therapy

After introducing a retinal pigment epithelial cell line to the subretinal space early in the progress of photoreceptor degeneration, most inner retinal changes were held in abeyance for up to at least 10 months of age, an encouraging finding.

Grafting of ARPE-19 and Schwann cells to the subretinal space in RCS rats.

Both hRPE and hSC grafts can survive and rescue photoreceptors for a substantial time after grafting and the fact that rescue occurred beyond the area of donor cell distribution suggests that diffusible factors are involved, raising the possibility that the two cell types function in a similar manner to rescue photoresceptors.