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Neural Regen Res. 2020 Mar;15(3):425-437. doi: 10.4103/1673-5374.266048.

Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans.

Author information

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; Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; University College of London Division of Surgery & Interventional Science, Center for Nanotechnology & Regenerative Medicine, University College London, London, UK.
2
University College of London Division of Surgery & Interventional Science, Center for Nanotechnology & Regenerative Medicine, University College London, London, UK; Department of Physical Medicine and Rehabilitation, The University of Texas Health Science Center at Houston; The Institute for Rehabilitation and Research Memorial Hermann Research Center, The Institute for Rehabilitation and Research Memorial Hermann Hospital, Houston, TX, USA.
3
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; Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School; Department of Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, USA.

Abstract

The central nervous system is known to have limited regenerative capacity. Not only does this halt the human body's reparative processes after central nervous system lesions, but it also impedes the establishment of effective and safe therapeutic options for such patients. Despite the high prevalence of stroke and spinal cord injury in the general population, these conditions remain incurable and place a heavy burden on patients' families and on society more broadly. Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments, utilizing stem cells-based strategies, biologically active molecules, nanotechnology, exosomes and highly tunable biodegradable systems (e.g., certain hydrogels). Although there are studies demonstrating promising preclinical results, safe clinical translation has not yet been accomplished. A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment, and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury. Such an ideal model does not currently exist, but it seems that the nonhuman primate model is uniquely qualified for this role, given its close resemblance to humans. This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation. In addition, it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

KEYWORDS:

animal models; central nervous system regeneration; clinical translation; exosomes; hydrogels; neural tissue engineering; nonhuman primates; spinal cord injury; stem cells; stroke

PMID:
31571651
DOI:
10.4103/1673-5374.266048
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