Grafted Human iPSC-Derived Neural Progenitor Cells Express Integrins and Extend Long-Distance Axons Within the Developing Corticospinal Tract

Following spinal cord injury, the regeneration of motor axons, such as those in the corticospinal tract (CST), is severely limited. This limitation is due to the inhibitory environment at the injury site and the reduced expression of growth-promoting proteins like integrins in mature neurons. Integrins are receptors that facilitate communication between the extracellular matrix and the cell cytoskeleton, promoting axon growth and guidance. This study uses human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) to increase the expression of α9 integrin within the developing rat CST. The researchers found that human NPCs express endogenous levels of both α9 and β1 integrin subunits, as well as cortical neuron markers. Overexpression of α9 integrin in these cells resulted in increased neurite outgrowth in the presence of tenascin-C (TN-C), a protein involved in development and injury response.

• 1
  Increasing α9 integrin expression in human iPSC-derived NPCs enhances neurite outgrowth in vitro, suggesting a functional role for α9 integrin in promoting axon growth.
• 2
  Human iPSC-derived NPCs, when transplanted into the developing sensorimotor cortex of rats, project axons within the endogenous CST, demonstrating their ability to integrate into the host's neural circuitry.
• 3
  Exogenous expression of α9 integrin is retained within the axonal compartment of human iPSC-derived NPCs for up to 8 weeks following transplantation, indicating sustained expression and potential long-term effects.