Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system
1 Laboratório de Neurobiologia Celular e Molecular, Programa de Terapia Celular e Bioengenharia, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Centro de Ciências da Saúde, Bl. G, Cidade Universitária, 21949-900, Rio de Janeiro, Brazil
2 Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem - INBEB, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
3 Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, Brazil
4 Laboratório de Neuroquímica, Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, UFRJ, Centro de Ciências da Saúde, Bl. C, Cidade Universitária, 21949-900, Rio de Janeiro, Brazil
Molecular Neurodegeneration 2012, 7:34 doi:10.1186/1750-1326-7-34Published: 13 July 2012
Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2) is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS).
Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL) region of the lumbar spinal cord (LSC) in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM) resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly.
We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.