Medical College of Wisconsin
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Mesenchymal stem cells facilitate axon sorting, myelination, and functional recovery in paralyzed mice deficient in Schwann cell-derived laminin. Glia 2011 Feb;59(2):267-77

Date

12/03/2010

Pubmed ID

21125647

Pubmed Central ID

PMC3118468

DOI

10.1002/glia.21099

Scopus ID

2-s2.0-78650252853 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

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.

Author List

Carlson KB, Singh P, Feaster MM, Ramnarain A, Pavlides C, Chen ZL, Yu WM, Feltri ML, Strickland S

Author

Karen-Sue B. Carlson MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acids
Animals
Axons
Cells, Cultured
Disease Models, Animal
Laminin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron, Transmission
Myelin P0 Protein
Myelin Sheath
Nerve Regeneration
Paralysis
Peripheral Blood Stem Cell Transplantation
Recovery of Function
Schwann Cells
Sciatic Nerve