Generation of a chimeric astrocytic rat spinal cord model by engraftment of human dorsal spinal neural stem/progenitor cells.

In the human spinal cord, astrocytes are the major glial cells. In vitro studies of human astrocytes are relatively simple. However, the straightforward nature of the in vitro environment and complex nature of the in vivo environment limit comprehensive investigations into the structure and function of human astrocytes. Additionally, in vivo studies of human astrocytes are further limited by ethical issues. This means there is an urgent need to develop effective in vivo models to study the structure and function of human astrocytes. Here, we first directed human embryonic stem cells to differentiate into human spinal cord dorsal neural stem/progenitor cells in vitro, before transplanting these cells into the gray matter of the cervical spinal cord (C5-T2 segments) of naïve nude rats to create a chimeric human astrocytic rat spinal cord model. The transplanted human spinal cord dorsal neural stem/progenitor cells survived for at least 20 months in the spinal cord environment of the rats, with over 90% differentiating into human astrocytes. These human astrocytes were able to migrate caudally for long distances along the white matter towards the spinal cord. They expressed astrocytic cytoskeletal proteins and functionally-related proteins, suggesting their maturation and structural integration into the rat spinal cord. Thus, this humanized astrocyte chimeric rat spinal cord model provides a valuable tool for studying the role of human spinal cord astrocytes in various spinal diseases.