Systemic Transplantation of Bone Marrow Mononuclear Cells Promotes Axonal Regeneration and Analgesia in a Model of Wallerian Degeneration.
Reinnervation timing after nerve injury is critical for favorable axonal regeneration, remyelination, and clinical improvement. Considering bone marrow mononuclear cells (BMMC) are easily obtained and readily available for transplant, this work analyzed the effect of BMMC systemic administration on nerve repair and pain behavior.



Adult rats with sciatic nerve crush were immediately and systemically injected BMMC through the caudal artery. Nontreated, sham and naïve rats were also included. Histological, immunohistochemical, biochemical, functional, and behavioral analyses were performed in nerves harvested from each group at different survival times.



Axons in BMMC-treated rats exhibited a more conserved morphological appearance than those in nontreated rats, as observed at different survival times both in semithin sections and ultrastructural analysis. BMMC-treated rats also showed a reduction in major myelin protein immunoreactive clusters 7 and 14 days postinjury, as compared with nontreated rats. Electrophysiological analysis showed BMMC treatment to slightly improve the amplitude of compound muscle action potential starting at 14 days postinjury. Finally, mechanical withdrawal threshold revealed a full preventive action against transient mechanical hypersensitivity in BMMC-treated rats.



These data demonstrate the efficiency of BMMC, systemically and noninvasively transplanted, in correcting morphological, functional and behavioral alterations resulting from peripheral nerve injury.
1 Departamento de Química Biológica, Facultad de Farmacia y Bíoquímica, Universidad de Buenos Aires. Instituto de Química y Físicoquímica Biológica Prof. Alejandro C. Paladini (IQUIFIB), UBA-CONICET, Buenos Aires. Argentina. 2 Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral-CONICET, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires, Argentina. 3 Instituto de Biología Celular y Neurociencias (IBCN), UBA-CONICET, Buenos Aires. Argentina. 4 Servicio de Anatomía Patológica Hospital Durand, Laboratorio de Enfermedades Neuromusculares Dra Taratuto, Argentina. 5 Servicio de Neurología, Hospital Español de Buenos Aires, Buenos Aires. Argentina.
Vanina
V
Usach
Mariana
M
Malet
Margarita
M
López
Lucía
L
Lavalle
Gonzalo
G
Piñero
María
M
Saccoliti
Alicia
A
Cueto
Pablo
P
Brumovsky
Alicia
A
Brusco
Patricia
P
Setton-Avruj
D000698:Analgesia / Q000379:methods*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D000071576:Crush Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration; D017288:Pain Threshold; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014855:Wallerian Degeneration
D015415:Biomarkers