Adipose-Derived Stromal Cells Contribute To Spinal Cord Repair But Are Not Neural-Crest Derived Stem Cells




Wrage, Philip Charles

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Neurodegeneration and injury to the nervous system are characterized by a loss of neurons - and often supporting glia - at the afflicted site. Neurons of the adult CNS are terminally differentiated, non-mitotic cells that are connected within specific circuits. These characteristics present a challenge to the development of treatments for degeneration or injury of the nervous system. The limited spatial distribution, as well as limited migration and differentiation potentials of adult NSCs, severely restrict the ability of adult NSCs to contribute to repair or regeneration in the wake of injury or degenerative disease progression. Adipose-derived adult stromal (ADAS) cells have been reported to give rise to cells of both mesodermal and ectodermal origin (e.g. osteocytes, chondrocytes, cardiac myocytes, neurons, and glia) and are easily harvested and cultured in vitro. Neural crest derived tissues have the extraordinary capacity to give rise to a wide range of tissue types: neurons and glia of the peripheral nervous system, adrenal glands, chondrocytes and osteocytes of the head and neck, smooth muscle cells of the cardiac outflow tract, and melanocytes among others. Given the reported ability of neural crest-derived cells and ADAS cells to give rise to bone, cartilage, muscle, and nerve tissues, I hypothesized that ADAS cells might be neural crest-derived cells that had migrated to the periphery, had remained resident within the adipose tissue of adult mammals, and had maintained early developmental plasticity. This hypothesis was not supported by lineage tracing experiments. Additionally, I found that ADAS cells were not capable of differentiating into functional neurons in vitro or in an in vivo model of spinal cord injury. However, ADAS cells altered the growth inhibitory environment of the lesioned cord and contributed to axon migration despite their inability to undergo neural differentiation. Based on these results, further research is warranted into the mechanisms by which ADAS cells create a growth permissive environment in the lesioned spinal cord.

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