title: Enhanced differentiation and delivery of mouse retinal progenitor cells using a micropatterned biodegradable thin-film polycaprolactone scaffold.
abstract: The deterioration of retinal tissue in advanced stages of retinitis pigmentosa and age-related macular degeneration and the lack of signaling cues for laminar regeneration are significant challenges highlighting the need for a tissue engineering approach to retinal repair. In this study, we fabricated a biodegradable thin-film polycaprolactone (PCL) scaffold with varying surface topographies using microfabrication techniques. Mouse retinal progenitor cells (mRPCs) cultured on PCL scaffolds exhibited enhanced potential to differentiate toward a photoreceptor fate in comparison to mRPCs cultured on control substrates, suggesting that PCL scaffolds are promising as substrates to guide differentiation of mRPCs toward a photoreceptor fate in vitro before transplantation. When cocultured with the retinal explants of rhodopsin null mice, mRPC/PCL constructs showed increased mRPC integration rates compared to directly applied dissociated mRPCs. Moreover, these mRPC/PCL constructs could be delivered into the subretinal space of rhodopsin null mice with minimal disturbance of the host retina. Whether cocultured with retinal explants or transplanted into the subretinal space, newly integrated mRPCs localized to the outer nuclear layer and expressed appropriate markers of photoreceptor fate. Thus, the PCL scaffold provides a platform to guide differentiation and organized delivery of mRPCs as a practical strategy to repair damaged retina.
authors.affiliation: 1 Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical School, Fudan University , Shanghai, China .
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Chi Wan
authors.initials: CW
authors.lastname: Ko
authors.forename: Petr Y
authors.initials: PY
authors.lastname: Baranov
authors.forename: Caio V
authors.initials: CV
authors.lastname: Regatieri
authors.forename: Stephen
authors.initials: S
authors.lastname: Redenti
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.forename: Jason
authors.initials: J
authors.lastname: Mighty
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tao
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Young
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D011091:Polyesters / Q000494:pharmacology*; D012160:Retina / Q000166:cytology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone; D002118:Calcium