Survival, migration and differentiation of retinal progenitor cells transplanted on micro-machined poly(methyl methacrylate) scaffolds to the subretinal space.
Stem and progenitor cells can be combined with polymer substrates to generate tissue equivalents in culture. The replacement of retinal tissue lost to disease or trauma using retinal progenitor cells (RPCs) delivered on polymer scaffolds and transplanted into the sub-retinal space of the damaged retina is a promising therapeutic strategy. Micromachining-based, ultra-thin PMMA poly(methyl methacrylate) scaffolds may provide a suitable cytoarchitectural environment for tissue engineering and transplantation to the diseased eye. Here, adhesion of RPCs to polymer, as well as migration and differentiation in the host retina were compared for PMMA scaffolds (6 microm thickness) with either smooth or porous (11 microm diameter) surface topography. RPCs were cultured under identical conditions on smooth or porous laminin-coated polymer scaffolds and transplanted into the subretinal space of C57BL/6 mice. RPCs could be cultured on both scaffolds with similar results, although transplantation with non-porous scaffolds showed limited RPC retention. Porous scaffolds demonstrated enhanced RPC adherence during transplantation and allowed for greater process outgrowth and cell migration into the host retinal layers. Integrated cells expressed the mature neuronal marker neurofilament-200 (nf-200), the glial marker glial fibrillary acidic protein (GFAP) and the retinal-specific marker recoverin. No host foreign body response was seen. In conclusion, ultra-thin film PMMA scaffolds micromachined to contain through pores retain adherent RPCs to a considerably greater extent than unmachined versions during the transplantation process and can serve as a biocompatible substrate for cell delivery in vivo.
Tao
Sarah
S
Department of Physiology, University of California, San Francisco, 1700 4th Street, San Francisco, California, USA.
Young
Conan
C
Redenti
Stephen
S
Zhang
Yiqin
Y
Klassen
Henry
H
Desai
Tejal
T
Young
Michael J
MJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D051603:Recoverin / Q000032:analysis; D012160:Retina / Q000166:cytology* / Q000378:metabolism / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering; D014183:Transplantation, Heterologous
D005904:Glial Fibrillary Acidic Protein; D051603:Recoverin; D019904:Polymethyl Methacrylate