Induced Pluripotent Stem Cells for Ischemic Stroke Treatment

Overview

Journal Front Neurosci

Date 2021 Jun 17

PMID 34135724

Citations 12

Authors

Ranran Duan

Yang Gao

Ruya He

Lijun Jing

Yanfei Li

Zhe Gong

Yaobing Yao

Tingting Luan

Chaopeng Zhang

Li Li

Yanjie Jia

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Exosomes derived from highly scalable and regenerative human progenitor cells promote functional improvement in a rat model of ischemic stroke.

Lee J, Var S, Chen D, Natera-Rodriguez D, Hassanipour M, West M bioRxiv. 2025; .

PMID: 39829810 PMC: 11741374. DOI: 10.1101/2025.01.07.631793.

Co-transplantation of autologous treg cells: A groundbreaking cell therapy for brain diseases.

Cheng Y, Zhang Y, Li P J Cereb Blood Flow Metab. 2024; 44(7):1246-1249.

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Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles.

Gao X, Liu D, Yue K, Zhang Z, Jiang X, Luo P Biomolecules. 2024; 14(3).

PMID: 38540796 PMC: 10967973. DOI: 10.3390/biom14030378.

Generation of induced pluripotent stem cells from rat fibroblasts and optimization of its differentiation into mature functional neurons.

Kuwar R, Zhang N, McQuiston A, Wen X, Sun D J Neurosci Methods. 2024; 406:110114.

PMID: 38522633 PMC: 11060920. DOI: 10.1016/j.jneumeth.2024.110114.

Stem cell-based ischemic stroke therapy: Novel modifications and clinical challenges.

Sun Y, Jiang X, Gao J Asian J Pharm Sci. 2024; 19(1):100867.

PMID: 38357525 PMC: 10864855. DOI: 10.1016/j.ajps.2023.100867.

References

Darsalia V, Kallur T, Kokaia Z . Survival, migration and neuronal differentiation of human fetal striatal and cortical neural stem cells grafted in stroke-damaged rat striatum. Eur J Neurosci. 2007; 26(3):605-14. DOI: 10.1111/j.1460-9568.2007.05702.x. View

Wichterle H, Lieberam I, Porter J, Jessell T . Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002; 110(3):385-97. DOI: 10.1016/s0092-8674(02)00835-8. View

Zhao Y, Yin X, Qin H, Zhu F, Liu H, Yang W . Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell. 2008; 3(5):475-9. DOI: 10.1016/j.stem.2008.10.002. View

Kim H, Kim J . A guide to genome engineering with programmable nucleases. Nat Rev Genet. 2014; 15(5):321-34. DOI: 10.1038/nrg3686. View

Robbins J, Price J . Human induced pluripotent stem cells as a research tool in Alzheimer's disease. Psychol Med. 2017; 47(15):2587-2592. PMC: 5635968. DOI: 10.1017/S0033291717002124. View

Kim G, Subash M, Yoon J, Jo D, Han J, Hong J . Neurogenin-1 Overexpression Increases the Therapeutic Effects of Mesenchymal Stem Cells through Enhanced Engraftment in an Ischemic Rat Brain. Int J Stem Cells. 2019; 13(1):127-141. PMC: 7119213. DOI: 10.15283/ijsc19111. View

Jensen M, Yan H, Krishnaney-Davison R, Al Sawaf A, Zhang S . Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model. J Stroke Cerebrovasc Dis. 2011; 22(4):304-8. PMC: 3295911. DOI: 10.1016/j.jstrokecerebrovasdis.2011.09.008. View

Kim J, Sebastiano V, Wu G, Arauzo-Bravo M, Sasse P, Gentile L . Oct4-induced pluripotency in adult neural stem cells. Cell. 2009; 136(3):411-9. DOI: 10.1016/j.cell.2009.01.023. View

Minassian A, Green C, Diedenhofen M, Vogel S, Hess S, Stoeber M . Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice. Front Cell Neurosci. 2020; 14:86. PMC: 7155295. DOI: 10.3389/fncel.2020.00086. View

10.

Shi Y, Desponts C, Do J, Hahm H, Scholer H, Ding S . Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell. 2008; 3(5):568-74. DOI: 10.1016/j.stem.2008.10.004. View

11.

Rhee Y, Ko J, Chang M, Yi S, Kim D, Kim C . Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest. 2011; 121(6):2326-35. PMC: 3104759. DOI: 10.1172/JCI45794. View

12.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

13.

Baker E, Platt S, Lau V, Grace H, Holmes S, Wang L . Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model. Sci Rep. 2017; 7(1):10075. PMC: 5577218. DOI: 10.1038/s41598-017-10406-x. View

14.

Lowrance S, Fink K, Crane A, Matyas J, Dey N, Matchynski J . Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke. Restor Neurol Neurosci. 2013; 33(4):579-88. DOI: 10.3233/RNN-130329. View

15.

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

16.

Kalra K, Chandrabose S, Ramasamy T, Kasim N . Advances in the Generation of Functional β-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus. Curr Drug Targets. 2018; 19(13):1463-1477. DOI: 10.2174/1389450119666180605112917. View

17.

Xia Y, Ling X, Hu G, Zhu Q, Zhang J, Li Q . Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke. Stem Cell Res Ther. 2020; 11(1):313. PMC: 7374834. DOI: 10.1186/s13287-020-01834-0. View

18.

Wei L, Cui L, Snider B, Rivkin M, Yu S, Lee C . Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol Dis. 2005; 19(1-2):183-93. DOI: 10.1016/j.nbd.2004.12.016. View

19.

Csobonyeiova M, Polak S, Zamborsky R, Danisovic L . Recent Progress in the Regeneration of Spinal Cord Injuries by Induced Pluripotent Stem Cells. Int J Mol Sci. 2019; 20(15). PMC: 6695701. DOI: 10.3390/ijms20153838. View

20.

Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T . Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2007; 26(1):101-6. DOI: 10.1038/nbt1374. View