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      3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development

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      Acta Biomaterialia
      Elsevier BV

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          Abstract

          No treatments exist to effectively treat many retinal diseases. Retinal pigmented epithelium (RPE) and neural retina can be generated from human embryonic stem cells/induced pluripotent stem cells (hESCs/hiPSCs). The efficacy of current protocols is, however, limited. It was hypothesised that generation of laminated neural retina and/or RPE from hiPSCs/hESCs could be enhanced by three dimensional (3D) culture in hydrogels. hiPSC- and hESC-derived embryoid bodies (EBs) were encapsulated in 0.5% RGD-alginate; 1% RGD-alginate; hyaluronic acid (HA) or HA/gelatin hydrogels and maintained until day 45. Compared with controls (no gel), 0.5% RGD-alginate increased: the percentage of EBs with pigmented RPE foci; the percentage EBs with optic vesicles (OVs) and pigmented RPE simultaneously; the area covered by RPE; frequency of RPE cells (CRALBP+); expression of RPE markers (TYR and RPE65) and the retinal ganglion cell marker, MATH5. Furthermore, 0.5% RGD-alginate hydrogel encapsulation did not adversely affect the expression of other neural retina markers (PROX1, CRX, RCVRN, AP2α or VSX2) as determined by qRT-PCR, or the percentage of VSX2 positive cells as determined by flow cytometry. 1% RGD-alginate increased the percentage of EBs with OVs and/or RPE, but did not significantly influence any other measures of retinal differentiation. HA-based hydrogels had no significant effect on retinal tissue development. The results indicated that derivation of retinal tissue from hESCs/hiPSCs can be enhanced by culture in 0.5% RGD-alginate hydrogel. This RGD-alginate scaffold may be useful for derivation, transport and transplantation of neural retina and RPE, and may also enhance formation of other pigmented, neural or epithelial tissue.

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          Author and article information

          Journal
          Acta Biomaterialia
          Acta Biomaterialia
          Elsevier BV
          17427061
          February 2017
          February 2017
          : 49
          : 329-343
          Article
          10.1016/j.actbio.2016.11.016
          27826002
          c1fd1628-4f3a-4d85-aa1e-6bf2118c32ac
          © 2017

          https://www.elsevier.com/tdm/userlicense/1.0/

          http://creativecommons.org/licenses/by-nc-nd/4.0/


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