Hayashi T, Abe K, Itoyama Y. Stroke.
These results suggest that NSCs are able to preserve the integrity of the BBB and help prevent further damage to the CNS following stroke [70, 204]. Human neural stem cells can migrate, differentiate, and integrate after intravenous transplantation in adult rats with transient forebrain ischemia. Brain Res. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Our ability to address neurovascular diseases will require multifaceted solutions, including pharmacological, cell replacement, genetic, and tissue engineering. Stroke. Oki K, Tatarishvili J, Wood J, Koch P, Wattananit S, Mine Y, Monni E, Tornero D, Ahlenius H, Ladewig J, et al.
Therefore, direct intraparenchymal transplantation may be advantageous over intravenous delivery to enhance NSC‐mediated tissue repair. NSCs derived in this manner have been tested in animal models of neurological disease and have proven to be therapeutic. Carbajal KS, Schaumburg C, Strieter R, Kane J, Lane TE. Shechter R, Schwartz M. Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer ‘if’ but ‘how’. This results in mitochondrial release of cytochrome c and subsequent activation of executioner caspases and downstream cell death pathways in neurons [138, 139]. Zhang L, Yi H, Xia XP, Zhao Y. Mohamad O, Drury-Stewart D, Song M, Faulkner B, Chen D, Yu SP, Wei L. Vector-free and transgene-free human iPS cells differentiate into functional neurons and enhance functional recovery after ischemic stroke in mice. Nakagomi T, Molnar Z, Nakano-Doi A, Taguchi A, Saino O, Kubo S, Clausen M, Yoshikawa H, Nakagomi N, Matsuyama T. Ischemia-induced neural stem/progenitor cells in the pia mater following cortical infarction. 2015;304:250–9.
Grafted NSC‐derived neurons are capable of differentiating into a wide array of mature neuron subtypes expressing dopaminergic neuron (Chang et al., 2013; Polentes et al., 2012; Zhang et al., 2013), GABAergic interneuron (Darsalia et al., 2007; Oki et al., 2012; Polentes et al., 2012; Zhang et al., 2013), medium spiny striatal projection neuron (Chang et al., 2013; Oki et al., 2012; Polentes et al., 2012; Zhang et al., 2013), and cortical neuron markers (Darsalia et al., 2007; Oki et al., 2012; Tornero et al., 2013). For these reasons, the recent advancements in direct differentiation of stable and expandable NSCs from adult somatic cells are promising for therapeutic applications [55]. Macrophages are a major initial infiltrate following stroke [109], and similar to microglia, these immune cells can exhibit functionally different phenotypes [110]. Similarly, transplantation of human iPSC (hiPSC)-NSCs into a stroke rodent model 24 h after ischemic reperfusion resulted in decreased levels of IgG, which is known to cross the compromised rodent BBB and leak into the brain parenchyma [70]. Jin K, Mao X, Xie L, Greenberg RB, Peng B, Moore A, Greenberg MB, Greenberg DA. 1998;439(3):373–6. Together, these studies indicate that neovascularization is a major mechanism of NSC‐mediated tissue and functional recovery after stroke. Hassani Z, O'Reilly J, Pearse Y, Stroemer P, Tang E, Sinden J, Price J, Thuret S. Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.
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