In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

Toru Yamashita; Jingwei Shang; Yumiko Nakano; Ryuta Morihara; Kota Sato; Mami Takemoto; Nozomi Hishikawa; Yasuyuki Ohta; Koji Abe

doi:10.1038/s41598-019-47482-0

In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

Toru Yamashita, Jingwei Shang, Yumiko Nakano, Ryuta Morihara, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journal › Article › peer-review

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Abstract

The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5–2.0 × 10⁷ /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.

Original language	English
Article number	10956
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-47482-0
Publication status	Published - Dec 1 2019

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title = "In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia",

abstract = "The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5–2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.",

author = "Toru Yamashita and Jingwei Shang and Yumiko Nakano and Ryuta Morihara and Kota Sato and Mami Takemoto and Nozomi Hishikawa and Yasuyuki Ohta and Koji Abe",

note = "Funding Information: This work was partly supported by a Grant-in-Aid for Scientific Research (B) 17H04196, (C) 17K10827 and Challenging Research 15K15527, and by Grants-in-Aid from the Research Committees (Mizusawa H, Nishizawa M, Sasaki H, and Aoki M) from the Ministry of Health, Labour and Welfare of Japan. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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AU - Yamashita, Toru

AU - Shang, Jingwei

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AU - Sato, Kota

AU - Takemoto, Mami

AU - Hishikawa, Nozomi

AU - Ohta, Yasuyuki

AU - Abe, Koji

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N2 - The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5–2.0 × 107 /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.

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In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

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