Bone marrow stromal cell therapy reduces proNGF and p75 expression in mice with experimental autoimmune encephalomyelitis.
Demyelination is prominent in experimental autoimmune encephalomyelitis (EAE). The receptor p75 and its high affinity ligand proNGF are required for oligodendrocyte death after injury. We hypothesize that bone marrow stromal cells (BMSCs) provide therapeutic benefit in EAE mice by reducing proNGF/p75 expression. PBS or BMSCs (2 x 10(circumflex)6) were administered intravenously on the day of EAE onset. Neurological function and demyelination areas were measured. Immunohistochemical staining was used to measure apoptotic oligodendrocytes, expression of proNGF and p75, and the relationship between proNGF and p75 in neural cells. proNGF was used to treat oligodendrocytes in culture with or without BMSCs. EAE mice exhibited neurological function deficit and demyelination, and expression of proNGF and p75 was increased. BMSC treatment improved functional recovery, reduced demyelination area and apoptotic oligodendrocytes, decreased expression of proNGF and p75 compared with PBS treatment. proNGF(+) cells colocalized with neural cell markers, while p75 colocalized with an oligodendrocytic marker, and proNGF colocalized with p75. proNGF induced apoptosis of oligodendrocytes in vitro, and p75 antibody blocked this apoptotic activity. BMSCs reduced p75 expression and apoptotic activity in oligodendrocytes with proNGF treatment. BMSC treatment benefits on EAE mice may be fostered by decreasing the cellular expression of proNGF and p75, thereby reducing oligodendrocyte death.
Zhang
Jing
J
Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
Brodie
Chaya
C
Li
Yi
Y
Zheng
Xuguang
X
Roberts
Cynthia
C
Lu
Mei
M
Gao
Qi
Q
Borneman
Jade
J
Savant-Bhonsale
Smita
S
Elias
Stanton B
SB
Chopp
Michael
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020127:Recovery of Function; D017154:Stromal Cells
D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C489226:pro-nerve growth factor, mouse; D020932:Nerve Growth Factor