Abstract
Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms.
Highlights
Worldwide, stroke is one of the most serious brain disorders [1]
Copositive cells were significantly higher in the ep-iPSCNPC group than the other groups (Figure 5(b)). These findings suggest that ep-Induced pluripotent stem cells (iPSCs)-neural precursor cells (NPCs) promote subventricular zone (SVZ) neurogenesis in the damaged brain following stroke via a paracrine mechanism
The generation of clinical-grade iPSC-NPCs in integration- and xeno-free conditions is critically important for clinical translation in the future
Summary
Stroke is one of the most serious brain disorders [1]. Some patients show spontaneous recovery after stroke, more than 30% of patients have permanent functional deficits despite intensive efforts of rehabilitation [2]. Residual deficits following stroke present serious economic and mental problems for patients and their families. Treatment of ischemic stroke depends on the use of tissue-type plasminogen activator, a thrombolytic agent that works only within 4.5 h after the onset of stroke [3]. There is currently no established treatment for the chronic phase of stroke. Restoration of neurons in the damaged brain is a prerequisite for functional improvement in patients with chronic stroke
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
