Mesenchymal stem cells facilitate axon sorting, myelination, and functional recovery in paralyzed mice deficient in Schwann cell-derived laminin.
Peripheral nerve function depends on a regulated process of axon and Schwann cell development. Schwann cells interact with peripheral neurons to sort and ensheath individual axons. Ablation of laminin γ1 in the peripheral nervous system (PNS) arrests Schwann cell development prior to radial sorting of axons. Peripheral nerves of laminin-deficient animals are disorganized and hypomyelinated. In this study, sciatic nerves of laminin-deficient mice were treated with syngenic murine adipose-derived stem cells (ADSCs). ADSCs expressed laminin in vitro and in vivo following transplant into mutant sciatic nerves. ADSC-treatment of mutant nerves caused endogenous Schwann cells to differentiate past the point of developmental arrest to sort and myelinate axons. This was shown by (1) functional, (2) ultrastructural, and (3) immunohistochemical analysis. Treatment of laminin-deficient nerves with either soluble laminin or the immortalized laminin-expressing cell line 3T3/L1 did not overcome endogenous Schwann cell developmental arrest. In summary, these results indicate that (1) laminin-deficient Schwann cells can be rescued, (2) a cell-based approach is beneficial in comparison with soluble protein treatment, and (3) mesenchymal stem cells modify sciatic nerve function via trophic effects rather than transdifferentiation in this system.
Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, New York 10065, USA.
Karen B
KB
Carlson
Prabhjot
P
Singh
Moses M
MM
Feaster
Anita
A
Ramnarain
Constantine
C
Pavlides
Zu-Lin
ZL
Chen
Wei-Ming
WM
Yu
M Laura
ML
Feltri
Sidney
S
Strickland
D000596:Amino Acids; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007797:Laminin / Q000172:deficiency* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018993:Myelin P0 Protein / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics; D010243:Paralysis / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D012583:Schwann Cells / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology
D000596:Amino Acids; D007797:Laminin; D018993:Myelin P0 Protein; C098463:dolaisoleucine; C089141:laminin gamma 1