FIGURE 3.

In vivo neuroregeneration and reduced inflammation after cell conversion in NHP ischemic stroke model. (A) Serial brain sections across the injury core illustrating the neuronal density (NeuN staining) in the monkey cortex following ischemic injury and viral injection. Note that both NeuN signal and cortical tissue were significantly impaired in the mCherry-injected side (left), but significantly rescued in the NeuroD1-mcherry injected side (right). Viral infection was conducted at 21 days post stroke (dps), and immunostaining analysis was performed at 2 months post viral injection (for all panels A–D). Scale bar, 2000 μm. (B) Representative high magnification images of neuronal density (NeuN, green) and viral infection (mCherry, red) in the monkey cortex. NeuroD1-mCherry infected areas always showed a significantly increased neuronal density. Nuclei were counterstained with DAPI (blue). Scale bar, 50 μm. (C) Both low and high magnification images illustrating the astrocytes (GFAP, green) infected by control virus mCherry alone (red, left panels), but rarely in the NeuroD1-mCherry infected areas (right panels). Note that while rarely co-localizing with NeuroD1-mCherry, GFAP⁺ astrocytes always persisted in the converted area and even showed less reactive morphology, indicating that astrocytes were not depleted after conversion. Scale bar, 200 μm (low mag), 20 μm (high mag). (D) Representative images in low and high magnification illustrate a reduction of microglia and macrophage (Iba1, green) in the NeuroD1-infected areas (bottom row) following ischemic stroke, comparing to the control side (top row). Nuclei are DAPI stained (blue). Scale bar, 1000 μm (low mag, left panels), 200 μm (higher mag, middle panels), 50 μm (highest mag, right panels).