Stem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors

Chapter
Part of the Springer Series in Translational Stroke Research book series (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.

Keywords

Aging Stroke Therapies Stem cells G-CSF BM-MSC BM-MNC 

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

Notes

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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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Medicine EssenEssenGermany
  2. 2.Department of Functional SciencesUniversity of Medicine and Pharmacy of CraiovaCraiovaRomania
  3. 3.Griffith University School of MedicineGold CoastAustralia
  4. 4.Neurological Service, San Camillo de’ Lellis General Hospital, Rieti; and the Neurological Section, Neuro-epidemiology Unit, SMDNCentre for Cardiovascular Medicine and Cerebrovascular Disease PreventionL’AquilaItaly

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