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

Lavik, EB; Klassen, Henry; Warfvinge, Karin; Langer, Robert; Young, M. J.

doi:10.1016/j.biomaterials.2004.08.022

Cited by 164 publications

(146 citation statements)

References 24 publications

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“…Although various techniques have been performed to promote the neuronal integration between the transplant and the host retina (Kinouchi et al, 2003;Lavik et al, 2005), no clear evidence of functional synaptic connectivity has yet been published. However, preliminary data from our group have shown that neurons in the transplant can be trans-synaptically labeled from the visually responsive site in the SC (Seiler et al, 2005b; manuscript submitted).…”

Section: Discussionmentioning

confidence: 99%

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

Seiler

Thomas

Chen

et al. 2008

Experimental Eye Research

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The aim of this study was to evaluate the functional efficacy of retinal progenitor cell (RPC) containing sheets with BDNF microspheres following subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 RPCs derived from human placental alkaline phosphatase (hPAP) expressing transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres containing brain-derived neurotrophic factor (BDNF) and transplanted into the subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls received transplants without BDNF or BDNF microspheres alone. Visual function was monitored using optokinetic head-tracking behavior. Visually evoked responses to varying light intensities were recorded from the superior colliculus (SC) by electrophysiology at 60 days after surgery. Frozen sections were studied by immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking was significantly improved in rats that received BDNF-coated RPC sheets. Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF transplants (57%) responded to a ''low light'' intensity of 1 cd/m 2 in a confined SC area. With bright light, the onset latency of SC responses was restored to a nearly normal level in BDNF-treated transplants. No significant improvement was observed in the BDNF-only and no surgery transgenic control rats. The bipolar synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and abnormal distribution of the host retina, both with or without BDNF treatment. Red-green cones were significantly reduced in the host retina overlying the transplant in the BDNF-treated group. In summary, BDNF coating improved the functional efficacy of RPC grafts. The mechanism of the BDNF effectsdeither promoting functional integration between the transplant and the host retina and/or synergistic action with other putative humoral factors released by the RPCsdstill needs to be elucidated. Ó 2007 Elsevier Ltd. All rights reserved.Keywords: retinal transplantation; superior colliculus; head-tracking behavior; BDNF microsphere; retinal progenitor cells; S334terAbbreviations: BDNF, brain-derived neurotrophic factor; DAPI, 4 0 6 0 -diamidino-2-phenylindole hydrochloride; CNS, central nervous system; GC, ganglion cell layer; H, host retina; hPAP, human placental alkaline phosphatase; IN, inner nuclear layer; IP, inner plexiform layer; mGluR6, metabotropic glutamate receptor 6 (synaptic receptor on bipolar cells); ms, milliseconds; ON, outer nuclear layer; OP, outer plexiform layer; OS, outer segments; PBS, phosphate-buffered saline; PKC, protein kinase C (marker for rod bipolar cells); PLGA, poly-lactide-co-glycolide; PSD-95, post-synaptic density protein 95 (post-synaptic marker on bipolar cell dendrites); RG-opsin, red-green opsin; RPC, retinal progenitor cells; SC, superior colliculus; RCS, Royal College of Surgeons; RPE, retinal pigment epithelium; T, transplant.

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Section: Discussionmentioning

confidence: 99%

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

Seiler

Thomas

Chen

et al. 2008

Experimental Eye Research

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“…Porous poly(L-lactic acid) and poly(lactic-co-glycolic acid) scaffolds with 100-to 200-mm pores oriented normal to the plane of the scaffold cause murine retinal progenitor cells to adhere and align with the scaffold, re-creating the polarized organization of photoreceptors. 102 In addition to controlling the gross porous structure, it is possible to imprint fine patterns into the surface of a scaffold. Femtosecond laser ablation produces micropatterns of niche-like groves in collagen scaffolds that trap and support the growth of rat BMSCs.…”

Section: Scaffoldsmentioning

confidence: 99%

Review:Ex VivoEngineering of Living Tissues with Adult Stem Cells

et al. 2006

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Adult stem cells have the potential to revolutionize regenerative medicine with their unique abilities to self-renew and differentiate into various phenotypes. This review examines progress and challenges in ex vivo tissue engineering with adult stem cells. These rare cells are harvested from a variety of tissues, including bone marrow, adipose, skeletal muscle, and placenta, and differentiate into cells of their own lineage and in some cases atypical lineages. Insight into the stem cell niche leads to the identification of matrix components, soluble factors, and physiological conditions that enhance the ex vivo amplification and differentiation of stem cells. Scaffolds composed of metals, naturally occurring materials, and synthetic polymers organize stem cells into complex spatial groupings that mimic native tissue. Cell signals from covalently bound ligands and slowly released regulatory factors in scaffolds direct stem cell fate. Future advances in stem cell biology and scaffold design will ultimately improve the efficacy of tissue substitutes as implants, in research, and as extracorporeal devices.

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“…Most of the surface was covered with polyelectrolytes and the islands were green over the whole thickness. If the number of layers was increased until the formation of (PLL/CSA) 20 /PLL FITC , the film became uniform and fluorescence was visualized over a thickness of ~2 µm (Figure 4b, b'). This film thus probably resulted from coalescence of islands appearing during deposition of the 10 first bilayers, as was also concluded for PLL/HA.…”

Section: Analysis Of Film Growth: Physicochemical Characterisation Ofmentioning

confidence: 99%

“…Specifically, stem cell based therapy is a promising approach in neurodegenerative disorders. 15,19 Recently, Lavik and coworkers 20 used blends of poly(L-lactic acid) and poly(lactic-co-glycolic acid) foams to deliver retinal progenitor cells to the subretinal space of rat eyes, promoting differentiation of these cells into functional photoreceptors through the laminar organization and structural guidance channels provided.…”

Section: Introductionmentioning

confidence: 99%