Original scientific paper
https://doi.org/10.3325/cmj.2018.59.203
Transplantation of neural stem cells in the mouse model of ischemic brain stroke and expression of genes involved in programmed cell death
Valentina Hribljan
; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
Iva Salamon
; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
Arijana Đemaili
; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
Ivan Alić
; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
Dinko Mitrečić
orcid.org/0000-0003-4836-1721
; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
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 oneway
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 downregulated
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.
Keywords
Hrčak ID:
239174
URI
Publication date:
16.10.2018.
Visits: 918 *