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Fabrication of degradable polymer scaffolds to direct the integration and differentiation of retinal progenitors

Lavik, EB; Klassen, H; Warfvinge, Karin LU ; Langer, R and Young, MJ (2005) In Biomaterials 26(16). p.3187-3196
Abstract
Retinal progenitor cells (RPCs) are self-renewing cells capable of differentiating into the different retinal cell types including photoreceptors, and they have shown promise as a source of replacement cells in experimental models of retinal degeneration. We hypothesized that a biodegradable polymer scaffold could deliver these cells to the subretinal space in a more organized manner than bolus injections, while also providing the graft with laminar organization and structural guidance channels. We fabricated highly porous scaffolds from blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) using a variety of techniques to produce pores oriented normal to the plane of the scaffold. RPCs were seeded on the polymer scaffolds and... (More)
Retinal progenitor cells (RPCs) are self-renewing cells capable of differentiating into the different retinal cell types including photoreceptors, and they have shown promise as a source of replacement cells in experimental models of retinal degeneration. We hypothesized that a biodegradable polymer scaffold could deliver these cells to the subretinal space in a more organized manner than bolus injections, while also providing the graft with laminar organization and structural guidance channels. We fabricated highly porous scaffolds from blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) using a variety of techniques to produce pores oriented normal to the plane of the scaffold. RPCs were seeded on the polymer scaffolds and cultured for 14 days. Seeded scaffolds were then either fixed for characterization or used in an explant or in vivo rat model. The, scaffolds were fully covered by RPCs in 3 days. Attachment of RPCs to the polymer scaffold was associated with down-regulation of immature markers and up-regulation of markers of differentiation. This suggests that the scaffold may promote differentiation of RPCs. The seeded cells elaborated cellular processes and aligned in the scaffold in conjunction with degenerating retinal explants. The cells also exhibited morphologies consistent with photoreceptors including a high degree of polarization of the cells. This data suggests that the scaffold may be a means to assist in the promotion of photoreceptor phenotypes. Implantation of the seeded scaffold into the rat eye is associated with increased RPC survival. Taken together, these data suggest that these polymer scaffolds provide a useful means for delivering RPCs to the subretinal space and may assist in the formation of retinal cell phenotypes, although it is clear that more cues are needed to direct the differentiation of RPCs into functional photoreceptors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
PLGA, retinal progenitor cells, retina, polymer, scaffold
in
Biomaterials
volume
26
issue
16
pages
3187 - 3196
publisher
Elsevier
external identifiers
  • wos:000226675500040
  • pmid:15603813
  • scopus:10644281300
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2004.08.022
language
English
LU publication?
yes
id
c7b75a4c-48b6-45a4-af73-da744049cf2e (old id 254976)
date added to LUP
2007-08-13 13:15:12
date last changed
2017-08-27 03:50:56
@article{c7b75a4c-48b6-45a4-af73-da744049cf2e,
  abstract     = {Retinal progenitor cells (RPCs) are self-renewing cells capable of differentiating into the different retinal cell types including photoreceptors, and they have shown promise as a source of replacement cells in experimental models of retinal degeneration. We hypothesized that a biodegradable polymer scaffold could deliver these cells to the subretinal space in a more organized manner than bolus injections, while also providing the graft with laminar organization and structural guidance channels. We fabricated highly porous scaffolds from blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) using a variety of techniques to produce pores oriented normal to the plane of the scaffold. RPCs were seeded on the polymer scaffolds and cultured for 14 days. Seeded scaffolds were then either fixed for characterization or used in an explant or in vivo rat model. The, scaffolds were fully covered by RPCs in 3 days. Attachment of RPCs to the polymer scaffold was associated with down-regulation of immature markers and up-regulation of markers of differentiation. This suggests that the scaffold may promote differentiation of RPCs. The seeded cells elaborated cellular processes and aligned in the scaffold in conjunction with degenerating retinal explants. The cells also exhibited morphologies consistent with photoreceptors including a high degree of polarization of the cells. This data suggests that the scaffold may be a means to assist in the promotion of photoreceptor phenotypes. Implantation of the seeded scaffold into the rat eye is associated with increased RPC survival. Taken together, these data suggest that these polymer scaffolds provide a useful means for delivering RPCs to the subretinal space and may assist in the formation of retinal cell phenotypes, although it is clear that more cues are needed to direct the differentiation of RPCs into functional photoreceptors.},
  author       = {Lavik, EB and Klassen, H and Warfvinge, Karin and Langer, R and Young, MJ},
  issn         = {1878-5905},
  keyword      = {PLGA,retinal progenitor cells,retina,polymer,scaffold},
  language     = {eng},
  number       = {16},
  pages        = {3187--3196},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {Fabrication of degradable polymer scaffolds to direct the integration and differentiation of retinal progenitors},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2004.08.022},
  volume       = {26},
  year         = {2005},
}