Retinoic acid-pretreated Wharton’s jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury

Abstract

Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

All trans-retinoic acid protects against acute ischemic stroke by modulating neutrophil functions through STAT1 signaling

“…Modulating post-stroke neural inflammation has been suggested as an important therapeutic strategy in cerebral ischemia [32]. All-trans retinoic acid is a well-established inflammatory modulator which has raised interest in the field of stroke therapy [9, 10, 33–35]. The current study demonstrates that atRA prophylactic treatment modulates post-stroke neural inflammation through regulation of neutrophil functions.…”

Extracellular Vesicles Derived from Human Umbilical Cord Perivascular Cells Improve Functional Recovery in Brain Ischemic Rat via the Inhibition of Apoptosis

“…Our outcomes showed that EVs therapy after MCAO decreased neuronal apoptosis, increased neuronal density, reduced dark neurons and the infarct size and improved the sensorimotor function. Ample evidence exists on the efficacy of cell-based therapy for stroke [ 43 , 44 ] . MSCs-EVs are assumed as the main paracrine effects of MSCs and a reliable supersede with lower oncological risks [ 45 ] .…”

Triiodothyronine Improves Morphology and Up-regulates seladin-1 of neurospheres extracted from Subventricular Zone in Streptozotocin-induced rat model of Alzheimer's disease

“…Finally, quantification of data, its normalization to GAPDH and fold change comparison to the control were performed. 21 In Table 1, the nucleotide sequences of primers are shown.…”