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

Lookup NU author(s): Dr Nicola Hunt, Dr Dean Hallam, Dr Carla Jackson, Dr Jinju Chen, Professor Majlinda LakoORCiD

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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 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; 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 which 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.

Publication metadata

Author(s): Hunt NC, Hallam D, Karimi A, Mellough CB, Chen J, Steel DHW, Lako M

Publication type: Article

Publication status: Published

Journal: Acta Biomaterialia

Year: 2017

Volume: 49

Pages: 329-343

Print publication date: 01/02/2017

Online publication date: 05/11/2016

Acceptance date: 03/11/2016

Date deposited: 04/11/2016

ISSN (print): 1742-7061

ISSN (electronic): 1878-7568

Publisher: Elsevier BV

URL: http://dx.doi.org/10.1016/j.actbio.2016.11.016

DOI: 10.1016/j.actbio.2016.11.016

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