中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 605-613.doi: 10.4103/1673-5374.295269

• 综述:脑损伤修复保护与再生 •    下一篇

水凝胶递送细胞外囊泡在中风后运动功能恢复中的应用：临床转化的行为及神经影像学评估方法

  

  • 出版日期:2021-04-15 发布日期:2020-12-21

The use of hydrogel-delivered extracellular vesicles in recovery of motor function in stroke: a testable experimental hypothesis for clinical translation including behavioral and neuroimaging assessment approaches

Magdalini Tsintou1, 2, 3, #, Kyriakos Dalamagkas3, 4, 5, #, Tara L. Moore6, Yogesh Rathi1, 2, Marek Kubicki1, 2, Douglas L. Rosene6, Nikos Makris1, 2, 6, *   

  1. 1 Departments of Psychiatry and Neurology Services, Center for Neural Systems Investigations, Center for Morphometric Analysis, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;  2 Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;   3 University College of London Division of Surgery & Interventional Science, Center for Nanotechnology & Regenerative Medicine, University College London, London, UK;   4 Department of Physical Medicine and Rehabilitation, The University of Texas Health Science Center at Houston, Houston, TX, USA;   5 The Institute for Rehabilitation and Research Memorial Hermann Research Center, The Institute for Rehabilitation and Research Memorial Hermann Hospital, Houston, TX, USA;   6 Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA
  • Online:2021-04-15 Published:2020-12-21
  • Contact: Nikos Makris, MD, PhD, nikos@cma.mgh.harvard.edu.
  • Supported by:
    This work was supported by the National Center for Complementary and Integrative Health (NCCIH), No. R21AT008865 (to NM); the National Institute of Aging (NIA)/National Institute of Mental Health (NIMH), No. R01AG042512 (to NM).

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摘要： https://orcid.org/0000-0003-0425-3315 (Nikos Makris)

Abstract: Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimaging analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Key words: cortical injury, exosomes, extracellular vesicles, hydrogels, neural tissue engineering, neural tissue repair, neuroregeneration, non-human primates, stroke