Induced Pluripotent Stem Cells for Ischemic Stroke Treatment

But why go thru all the trouble of stem cells if exosomes are the reason for the benefits? Which must be why no one seems to be monitoring stem cell survival.

Application of stem cell-derived exosomes in ischemic diseases: opportunity and limitations

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Induced Pluripotent Stem Cells for Ischemic Stroke Treatment

Ranran Duan^1†, Yang Gao^1†, Ruya He^2†, Lijun Jing¹, Yanfei Li¹, Zhe Gong¹, Yaobing Yao¹, Tingting Luan¹, Chaopeng Zhang¹, Li Li^3* and Yanjie Jia^1*

• ¹Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ²The International Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ³Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.

Introduction

Stroke is one of the major central nervous system diseases associated with high disability and mortality rates, approximately 80% of the cases being ischemic stroke (Phipps and Cronin, 2020). Although there are many clinical treatment methods available currently for patients with ischemic stroke, including antiplatelet aggregation, anticoagulation, improving microcirculation, and improving brain metabolism, these do not have efficient regeneration and repair effects on the necrotic nerve cells in the ischemic area. The standard treatment method is to either use recombinant tissue plasminogen activator (rt-PA) or perform mechanical thrombectomy to restore blood flow. However, these treatments have certain limitations. The effective treatment time window of rt-PA is 4.5 h, and patients with large artery occlusion can be treated with thrombectomy within 6 h or even beyond 24 h of symptom onset. However, nearly 60% of patients did not achieve functional independence at 3 months after treatment in recent mechanical thrombectomy trials (Rabinstein, 2020; Shafie and Yu, 2021). When ischemic stroke occurs, apoptosis or necrosis of various cells is seen in the infarct areas. Therefore, the ideal treatment method would be to implant a certain type of cell that can replace the damaged cells. In recent years, stem cell transplantation technology has been successfully applied in heart disease modeling (Musunuru et al., 2018), diabetes mellitus (Kalra et al., 2018), macular degeneration (Bracha et al., 2017), spinal cord injury (Csobonyeiova et al., 2019), cartilage regeneration (Castro-Viñuelas et al., 2018), and graft-vs.-host disease (Bloor et al., 2020). Stem cell transplantation is also being gradually considered for the treatment of some nervous system diseases, such as Alzheimer’s disease (Robbins and Price, 2017), Parkinson’s disease (Cobb et al., 2018), amyotrophic lateral sclerosis (Csobonyeiova et al., 2017), Huntington’s disease (Tousley and Kegel-Gleason, 2016; Yoon et al., 2020), and ischemic stroke. In this review, we have summarized the progress that has been made in the development of cell therapy for ischemic stroke. We have particularly focused on the mechanism, current status, clinical application, development constraints, and future prospects of the application of induced pluripotent stem cells (iPSCs) in treating ischemic stroke.

Current Applications of Stem Cells

Stem cell transplantation technology is attractive as a novel option for the treatment of ischemic stroke, and utilizes different cell sources, including embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), umbilical cord-derived blood cells, adipose-derived MSCs, dental stem cells, iPSCs, and some immortalized cell lines; the most recent studies in this field have primarily focused on the first three stem cell types. Here, we have discussed the current applications of different stem cell types in ischemic stroke, especially the iPSC therapy.