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.
Highlights
Stroke is the world’s leading cause of adult disabilities
We investigated the possibility of in vivo direct reprogramming in stroke and its therapeutic effect in post-stroke mice
The number of green fluorescence protein (GFP)-positive cells was significantly larger in the mice brain that received a viral injection 3 days after transient middle cerebral artery occlusion (tMCAO) than in other groups (3 d, 96.2 ± 8.9; 7 d, 29.3 ± 19.1; 14 d, 4.0 ± 0.4; cell number/0.12 mm2, *p < 0.05 vs 7 d, #p < 0.05 vs 14 d, Fig. 1a–c)
Summary
Neuroprotective therapy[1], thrombolytic therapy and endovascular intervention have been conducted in the acute phase of a stroke, a large number of stroke survivors are still suffering from this disability[2,3]. Regenerative therapy that reconstructs a neuronal network in the chronic phase of a stroke has been highlighted as a second generation therapy for strokes[4,5]. The potential risks of tumorigenicity have raised safety concerns for post-stroke patients[7,8]. The therapeutic effect of in vivo direct reprogramming against stroke has not yet been assessed. We investigated the possibility of in vivo direct reprogramming in stroke and its therapeutic effect in post-stroke mice
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