title: Long-term efficacy and safety outcomes of transplantation of induced pluripotent stem cell-derived neurospheres with bioabsorbable nerve conduits for peripheral nerve regeneration in mice.
abstract: The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable nerve conduits coated with iPSc-derived neurospheres for use in peripheral nerve repair. Here, we examine the long-term efficacy and safety of using nerve conduits with iPSc technology for peripheral nerve repair in mice. The nerve conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% ε-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the nerve conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the nerve conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable nerve conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable nerve conduits has the potential to be a safe future tool for the treatment of peripheral nerve defects.
authors.forename: Takuya
authors.initials: T
authors.lastname: Uemura
authors.forename: Mikinori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Takuya
authors.initials: T
authors.lastname: Yokoi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002460:Cell Line; D048091:Guided Tissue Regeneration; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D009043:Motor Activity; D039902:Multipotent Stem Cells / Q000166:cytology; D009416:Nerve Regeneration; D020127:Recovery of Function; D044968:Regenerative Medicine; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology*; D018874:Spheroids, Cellular / Q000166:cytology*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*; D016896:Treatment Outcome