Cell Based Therapies for Ischemic Stroke: from Basic Science to Bedside

Overview

Journal Prog Neurobiol

Specialty Neurology

Date 2013 Dec 17

PMID 24333397

Citations 106

Authors

Xinfeng Liu

Ruidong Ye

Tao Yan

Shan Ping Yu

Ling Wei

Gelin Xu

Xinying Fan

Yongjun Jiang

R Anne Stetler

George Liu

Jieli Chen

Affiliations

Soon will be listed here.

Abstract

Cell therapy is emerging as a viable therapy to restore neurological function after stroke. Many types of stem/progenitor cells from different sources have been explored for their feasibility and efficacy for the treatment of stroke. Transplanted cells not only have the potential to replace the lost circuitry, but also produce growth and trophic factors, or stimulate the release of such factors from host brain cells, thereby enhancing endogenous brain repair processes. Although stem/progenitor cells have shown a promising role in ischemic stroke in experimental studies as well as initial clinical pilot studies, cellular therapy is still at an early stage in humans. Many critical issues need to be addressed including the therapeutic time window, cell type selection, delivery route, and in vivo monitoring of their migration pattern. This review attempts to provide a comprehensive synopsis of preclinical evidence and clinical experience of various donor cell types, their restorative mechanisms, delivery routes, imaging strategies, future prospects and challenges for translating cell therapies as a neurorestorative regimen in clinical applications.

Citing Articles

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Stem cell therapy as a promising approach for ischemic stroke treatment.

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GABAergic neurons differentiated from BDNF- and Dlx2-modified neural stem cells restore disrupted neural circuits in brainstem stroke.

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Oxygen-Glucose Deprived Peripheral Blood Mononuclear Cells Protect Against Ischemic Stroke.

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References

Jiang B, Xiao W, Shi Y, Liu M, Xiao X . Heat shock pretreatment inhibited the release of Smac/DIABLO from mitochondria and apoptosis induced by hydrogen peroxide in cardiomyocytes and C2C12 myogenic cells. Cell Stress Chaperones. 2005; 10(3):252-62. PMC: 1226023. DOI: 10.1379/csc-124r.1. View

Sugiyama T, Kuroda S, Osanai T, Shichinohe H, Kuge Y, Ito M . Near-infrared fluorescence labeling allows noninvasive tracking of bone marrow stromal cells transplanted into rat infarct brain. Neurosurgery. 2011; 68(4):1036-47. DOI: 10.1227/NEU.0b013e318208f891. View

Hayashi J, Takagi Y, Fukuda H, Imazato T, Nishimura M, Fujimoto M . Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain. J Cereb Blood Flow Metab. 2006; 26(7):906-14. DOI: 10.1038/sj.jcbfm.9600247. View

Williams R, Herrup K . The control of neuron number. Annu Rev Neurosci. 1988; 11:423-53. DOI: 10.1146/annurev.ne.11.030188.002231. View

Michalet X, Pinaud F, Bentolila L, Tsay J, Doose S, Li J . Quantum dots for live cells, in vivo imaging, and diagnostics. Science. 2005; 307(5709):538-44. PMC: 1201471. DOI: 10.1126/science.1104274. View

Buhnemann C, Scholz A, Bernreuther C, Malik C, Braun H, Schachner M . Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats. Brain. 2006; 129(Pt 12):3238-48. DOI: 10.1093/brain/awl261. View

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

Fisher M, Feuerstein G, Howells D, Hurn P, Kent T, Savitz S . Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke. 2009; 40(6):2244-50. PMC: 2888275. DOI: 10.1161/STROKEAHA.108.541128. View

Mir O, Savitz S . Stem cell therapy in stroke treatment: is it a viable option?. Expert Rev Neurother. 2013; 13(2):119-21. DOI: 10.1586/ern.12.164. View

10.

Riess P, Zhang C, Saatman K, Laurer H, Longhi L, Raghupathi R . Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury. Neurosurgery. 2002; 51(4):1043-52; discussion 1052-4. DOI: 10.1097/00006123-200210000-00035. View

11.

Song M, Mohamad O, Gu X, Wei L, Yu S . Restoration of intracortical and thalamocortical circuits after transplantation of bone marrow mesenchymal stem cells into the ischemic brain of mice. Cell Transplant. 2012; 22(11):2001-15. DOI: 10.3727/096368912X657909. View

12.

Zhu W, Mao Y, Zhao Y, Zhou L, Wang Y, Zhu J . Transplantation of vascular endothelial growth factor-transfected neural stem cells into the rat brain provides neuroprotection after transient focal cerebral ischemia. Neurosurgery. 2005; 57(2):325-33. DOI: 10.1227/01.neu.0000166682.50272.bc. View

13.

Veizovic T, Beech J, Stroemer R, Watson W, Hodges H . Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells. Stroke. 2001; 32(4):1012-9. DOI: 10.1161/01.str.32.4.1012. View

14.

Egashira Y, Sugitani S, Suzuki Y, Mishiro K, Tsuruma K, Shimazawa M . The conditioned medium of murine and human adipose-derived stem cells exerts neuroprotective effects against experimental stroke model. Brain Res. 2012; 1461:87-95. DOI: 10.1016/j.brainres.2012.04.033. View

15.

Adamczak J, Hoehn M . In vivo imaging of cell transplants in experimental ischemia. Prog Brain Res. 2012; 201:55-78. DOI: 10.1016/B978-0-444-59544-7.00004-4. View

16.

Zhang L, Li Y, Zhang C, Chopp M, Gosiewska A, Hong K . Delayed administration of human umbilical tissue-derived cells improved neurological functional recovery in a rodent model of focal ischemia. Stroke. 2011; 42(5):1437-44. DOI: 10.1161/STROKEAHA.110.593129. View

17.

He A, Jiang Y, Gui C, Sun Y, Li J, Wang J . The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning. Can J Cardiol. 2009; 25(6):353-8. PMC: 2722478. DOI: 10.1016/s0828-282x(09)70094-7. View

18.

Kim D, Schellingerhout D, Ishii K, Shah K, Weissleder R . Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke. 2004; 35(4):952-7. DOI: 10.1161/01.STR.0000120308.21946.5D. View

19.

Cho Y, Song H, Bhang S, Lee S, Kang B, Lee J . Therapeutic effects of human adipose stem cell-conditioned medium on stroke. J Neurosci Res. 2012; 90(9):1794-802. DOI: 10.1002/jnr.23063. View

20.

Li Y, Chopp M, Chen J, Wang L, Gautam S, Xu Y . Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000; 20(9):1311-9. DOI: 10.1097/00004647-200009000-00006. View