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Cellular and Molecular Approaches to Regeneration and Repair pp 47–71Cite as

Stem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors

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Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. The incidence of stroke increases significantly with age both in men and women with incidence rates accelerating above 70 years. Since stroke afflicts mostly the elderly comorbid patients it is highly desirable to test the efficacy of cell therapies in an appropriate animal stroke model. It has been noted that the potential for neurogenesis is also preserved in aged, stroke-injured brains and the environment of the aged brain is not hostile to cell therapies. However, there remain significant developmental and translational issues that remain to be resolved in future studies such as (1) Understanding the differentiation into specific phenotypes. Upon transplantation, the differentiated cells often de-differentiate; (2) Tumorigenesis remains a significant concern; (3) Anti-neuroinflammatory therapies is a potential target to promote regeneration and repair after brain injury and neurodegenerative conditions by stem cell therapy; (4) Efficacy of cell therapy can be enhanced by physical rehabilitation; (5) One potential weakness of the preclinical dataset is, however, the lack of proof in aged subjects. It is in fact a general drawback of preclinical evaluations of candidate stroke drugs that due to cost effectiveness and practicability most studies were done in young animals. A lack of data from aged subjects in preclinical studies may at least in part explain the failure of candidate neuroprotective drugs in clinical trials. The aged brain has compared to the young brain, an enhanced susceptibility to stroke and displays a limited recovery from an ischemic injury. Finally, a better understanding of potential risks of stem cell therapies in stroke shall make the translation of cell therapies safer. Likewise, awareness of may help improve their efficacy to achieve therapeutic success.

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Abbreviations

BBB:

Blood–brain barrier

BMECs:

Brain microvascular endothelial cells

BM-MNC:

Bone marrow-derived mononuclear cells

BM-MSC:

Bone marrow mesenchymal cells

ECA:

External carotid artery

EPC:

Endothelial progenitor cells

ESCs:

Embryonic stem cells

G-CSF:

(Granulocyte-Colony Stimulating Factor) Hematopoietic factor

hBMMSCs:

Mesenchymal cells of human origin

HSPC:

Hematopoietic stem/progenitor cells

iPSC:

Human-derived inducible pluripotent cells

MCA:

Middle cerebral artery

MCAO:

Middle cerebral artery occlusion

MRI:

Magnetic Resonance Imaging

MSCs:

Mesenchymal stem cells

NSCs:

Neural stem cells

SVZ:

Subventricular zone

UCB:

Umbilical-cord blood

VEGF:

Vascular endothelial growth factor

SHR:

Spontaneously hypertensive rat model

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Acknowledgments

This study has been supported by a UEFISCDI grant PN-II-RU-TE-2014-4-0705, “The impact of microglia phagocytosis of live neurons on the efficacy of stem cell therapy of stroke “No 165/2015.

Conflict of Interest: The author confirms that he has no conflict of interest to declare for this publication.

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Authors and Affiliations

  1. Department of Neurology, University of Medicine Essen, Essen, Germany

    Aurel Popa-Wagner

  2. Department of Functional Sciences, University of Medicine and Pharmacy of Craiova, Craiova, Romania

    Aurel Popa-Wagner

  3. Griffith University School of Medicine, Gold Coast Campus, Gold Coast, QLD, 4222, Australia

    Aurel Popa-Wagner

  4. Neurological Service, San Camillo de’ Lellis General Hospital, Rieti; and the Neurological Section, Neuro-epidemiology Unit, SMDN, Centre for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L’Aquila, Italy

    Mario Di Napoli

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  1. Aurel Popa-Wagner
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Correspondence to Aurel Popa-Wagner .

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Editors and Affiliations

  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, AHSP, Los Angeles, California, USA

    Paul A. Lapchak

  2. Department of Physiology, Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Popa-Wagner, A., Di Napoli, M. (2018). Stem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors. In: Lapchak, P., Zhang, J. (eds) Cellular and Molecular Approaches to Regeneration and Repair. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-66679-2_3

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