Bone marrow-derived Schwann cells achieve fate commitment--a prerequisite for remyelination therapy.
Schwann cell transplantation improves post-traumatic nerve regeneration in both PNS and CNS but sufficient numbers of immunocompatible cells are required for clinical application. Currently, Schwann cell-like cells derived from the bone marrow lack fate commitment and revert to a fibroblast-like phenotype upon withdrawal of differentiation-inducing factors. In recapitulation of embryonic events leading to Schwann cell maturation, we hypothesize that the Schwann cell-like cells acquire the switch to fate commitment through contact-dependent cues from incipient neurons of the developing dorsal root ganglia. To address this, Schwann cell-like cells derived from adult rat bone marrow were cocultured with neurons purified from embryonic dorsal root ganglia. A cell-intrinsic switch to the Schwann cell fate was achieved consistently and the cell progeny maintained expression of the markers S100 beta, p75(NTR) , GFAP, P0 and Sox 10 even without exogenous differentiation-inducing factors or neurons. In vitro formation of MBP-positive segments under myelinating conditions by the cell progeny was comparable to that by sciatic nerve-derived Schwann cells. Controls in which Schwann cell-like cells were barred from direct contact with neurons in coculture reverted to SMA/CD90-expressing myofibroblasts. We demonstrate therefore for the first time fate commitment among bone marrow-derived Schwann cells. The therapeutic potential of these cells may be tested in future transplantation studies. (206 words).
Shea
Graham K H
GK
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China.
Tsui
Alex Y P
AY
Chan
Ying Shing
YS
Shum
Daisy K Y
DK
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D003470:Culture Media; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology; D005727:Ganglia, Spinal / Q000166:cytology; D007797:Laminin / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D020890:Neuregulin-1 / Q000494:pharmacology; D009474:Neurons / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology*
D003470:Culture Media; D007797:Laminin; D004676:Myelin Basic Protein; D020890:Neuregulin-1; D010982:Platelet-Derived Growth Factor; D005576:Colforsin