Stem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors

  • Aurel Popa-WagnerEmail author
  • Mario Di Napoli
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


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.


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



Blood–brain barrier


Brain microvascular endothelial cells


Bone marrow-derived mononuclear cells


Bone marrow mesenchymal cells


External carotid artery


Endothelial progenitor cells


Embryonic stem cells


(Granulocyte-Colony Stimulating Factor) Hematopoietic factor


Mesenchymal cells of human origin


Hematopoietic stem/progenitor cells


Human-derived inducible pluripotent cells


Middle cerebral artery


Middle cerebral artery occlusion


Magnetic Resonance Imaging


Mesenchymal stem cells


Neural stem cells


Subventricular zone


Umbilical-cord blood


Vascular endothelial growth factor


Spontaneously hypertensive rat model



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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