Transplantation of neural stem cells in the mouse model of ischemic brain stroke and expression of genes involved in programmed cell death

Croat Med J. 2018 Oct 31;59(5):203-212. doi: 10.3325/cmj.2018.59.203.

Abstract

Aim: To analyze how neural stem cells (NSC) transplantation in the stroke-affected mouse brain influences the expression of genes involved in apoptosis-inducing factor (AIF)-mediated cell death – apoptosis inducing factor mitochondria associated 1 (Aifm1), ring finger protein 146 (Rnf146, Iduna), and cyclophilin A (CypA); necroptosis –receptor interaction protein kinase 1 (Ripk1), Ripk3, and mixed-lineage kinase domain-like protein (Mlkl); and apoptosis – Caspase 3 (Casp3) and Casp8.

Methods: Four groups of animals were used to obtain mRNA for quantitative reverse transcription polymerase chain reaction analysis: healthy animals (n = 3), animals with stroke (n = 4), animals with stroke treated by stem cell transplantation (n = 7), and animals with stroke treated by proliferation-supporting medium (n = 5). Ischemic brain injury was induced by transient left middle cerebral artery occlusion. Statistical analysis was performed using one-way analysis of variance with post-hoc Tukey test.

Results: NSC transplantation in the stroke-affected mouse brain significantly increased the expression of Iduna (P < 0.05), a gene-encoding protein with well-known protective effects on hypoxic damage, and significantly down-regulated the expression of damage-supportive genes, Casp3 (P < .01) and Aifm1 (P < 0.001). We were able to distinguish between the effect produced by stem cell transplantation (Iduna, Aifm1, Ripk3, Mlkl) and the effect produced by supporting the tissue with proliferation-supporting medium (Ripk1, Casp8).

Conclusion: Beside revealing some clearly positive effects of stem cells transplantation on the stroke-affected brain, our results suggest that the tissue response triggered by stem cells points toward the desired, regeneration-supporting levels of expression of a certain gene at a certain time point.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Inducing Factor / genetics
  • Brain Ischemia / genetics
  • Brain Ischemia / therapy*
  • Caspases / genetics
  • Cell Differentiation
  • Cyclophilin A / genetics
  • Disease Models, Animal*
  • Female
  • Gene Expression Regulation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Stem Cells / transplantation*
  • Protein Kinases / genetics
  • RNA, Messenger / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cell Transplantation*
  • Stroke / genetics
  • Stroke / therapy*
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Apoptosis Inducing Factor
  • AIFM1 protein, mouse
  • RNA, Messenger
  • Rnf146 protein, mouse
  • Ubiquitin-Protein Ligases
  • MLKL protein, mouse
  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse
  • Ripk3 protein, mouse
  • Caspases
  • Cyclophilin A