New approaches for brain repair—from rescue to reprogramming

Abstract

The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New approaches using stem-cell-derived cell products and direct cell reprogramming have opened up the possibility of reconstructing neural circuits and achieving better repair. In this Review we briefly summarize the history of neural repair and then discuss these new therapeutic approaches, especially with respect to chronic neurodegenerative disorders.

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Fig. 1: Strategies to repair the diseased brain.
Fig. 2: Strategies for in situ repair.

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Acknowledgements

R.A.B. is funded by the NIHR Biomedical Research Centre in Cambridge, Cure PD, PDUK, European Research Council under the European Union’s Seventh Framework Programme: FP/2007-2013 NeuroStemcellRepair (no. 602278), Wellcome Trust MRC Stem Cell Institute and MRC UKRMP PSCP. He has received consultancy payments from FCDI and LCT. M.G. is funded by the German Research Foundation (CRC870, SPP1738, 1757, EXC1010 Synergy), The Ministry of Science and Research (MAIV), ERANET and the ERC (ChroNeuroRepair). M.P. receives funding from the New York Stem Cell Foundation, the European Research Council under the European Union’s Seventh Framework Programme: FP/2007-2013 NeuroStemcellRepair (no. 602278) and ERC Grant Agreement no. 30971, the Swedish Research Council and the Strategic Research Area Multipark at Lund University. M.P. is a New York Stem Cell Foundation Robertson Investigator. We thank D. Daft for her help in the preparation of this manuscript.

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Nature thanks P. Arlotta, J. Takahashi and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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All three authors contributed to the design, writing and critical review of this manuscript.

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Correspondence to Roger A. Barker or Magdalena Götz or Malin Parmar.

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M.P. is the owner of Parmar Cells AB and co-inventor on US patent applications 15/093,927 owned by Biolamina AB and EP17181588 owned by Miltenyi Biotec. Patent WO 2015/114059 A1 patents the use of BCL2 in reprogramming. R.A.B. and M.G. have no competing interests.

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Barker, R.A., Götz, M. & Parmar, M. New approaches for brain repair—from rescue to reprogramming. Nature 557, 329–334 (2018). https://doi.org/10.1038/s41586-018-0087-1

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