Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms

Prog Neurobiol. 2017 Nov;158:94-131. doi: 10.1016/j.pneurobio.2017.07.004. Epub 2017 Jul 23.


Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation. In this review, we investigate clinically relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose tissue-derived stem cells, breast milk-derived stem cells, menstrual blood-derived stem cells, dental tissue-derived stem cells, induced pluripotent stem cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c-mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal cells (SB623), comparing their potential efficacy to sequester stroke-induced neuroinflammation and their feasibility as translational clinical cell sources. To this end, we highlight that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti-inflammatory effects in stroke both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory action against stroke complements the regenerative processes of cell replacement and neurotrophic factor secretion conventionally ascribed to cell-based therapy in neurological disorders.

Keywords: Apoptosis; Cell death; Cell transplantation; Chronic inflammation; Secondary injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Death / physiology*
  • Humans
  • Inflammation / etiology
  • Inflammation / therapy*
  • Stem Cell Transplantation*
  • Stroke / immunology*
  • Stroke / therapy*