Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

Exp Gerontol. 2017 Aug:94:73-77. doi: 10.1016/j.exger.2017.01.008. Epub 2017 Jan 14.

Abstract

Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains.

Conclusion: While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time.

Keywords: Aging; G-CSF; Hypothermia; Stem cells; Stroke; Therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Disease Models, Animal
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation*
  • Mesenchymal Stem Cell Transplantation*
  • Neurogenesis*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*
  • Recovery of Function
  • Stem Cell Niche*
  • Stroke / metabolism
  • Stroke / pathology
  • Stroke / physiopathology
  • Stroke / surgery*

Substances

  • Granulocyte Colony-Stimulating Factor