Fig. 2

Tissue-Engineered Approaches for In vivo Transplantation. A A schematic illustration of transplantation of RPE cell suspension into neural rerina. (a) Micropipette containing cell suspension is positioned adjacent to neural retina. (b) Small amount of buffered salt solution (BSS) at tip of the pipette is slowly injected through retina into subretinal space. As bleb detachment forms, patches of host RPE cells lift off with neural retina, creating areas of bare Bruch's membrane. (c) With continued injection, cell suspension enters subretinal space. (d) Reattachment of retina occurs within 24 to 48 h of the RPE cell transplantation. (e) SEM image of two attached RPE cells onto the bare BrM surface one hour after injection [50]. B Biodegradable 3D gelatin, chondroitin sulfate, and hyaluronic acid (GCH) scaffold for retina cell differentiation and transplant. (a) Scanning electron micrograph shows three faces of a block of scaffold. (b) A higher magnification of one face. Light micrograph (c) and scanning electron micrograph (d) show embryoid bodies on the scaffold one-day post-seeding. (e) One-week post-seeding, cultures were stained with DAPI (blue) to reveal cell nuclei. Three-dimensional reconstruction from confocal micrographs demonstrated that cells migrated the thickness of the scaffold. (f) After three weeks, cells homogenously populated most of the scaffold, but acellular areas were present [52]. C Transplantation of organoid-derived retina-like sheets with rd1 host retina. Schematic diagrams show three typical patterns of integration with rd1 host retina of the transplanted grafts. (a) Pattern 1: laminar interception. Graft INL was present between host INL and graft ONL. (b) Pattern 2: direct contact. The graft ONL was adjacent to the host INL. (c) Pattern 3: cell integration. The graft ONL structure was disorganized, similar to what was observed for cell transplantation. (d) A typical image of pattern 1. RHODOPSIN + photoreceptors from DD16 Nrl-GFP miPSC-derived retinal sheets migrate toward the host retina (white arrowhead). H, host; G, graft. (e) A typical image of pattern 2. DD16 Nrl-GFP miPSC-derived retinal sheets show structured ONL directly contacting host INL. H, host; G, graft. (f) A typical image of pattern 3. DD18 Rx-GFP mESC-derived retinal grafts show disorganized patterns similar to those observed for cell transplantation. H, host; G, graft. Scale bars, (B) a, 1000 μm; b&c, 500 μm; d, 100 μm; e&f, scale in μm. (C) d-f, 50 μm (D–F); I, 20 μm. Figures were adapted with permission from [51,52,53]