Intracarotid Transplantation of Skin-Derived Precursor Schwann Cells Promotes Functional Recovery After Acute Ischemic Stroke in Rats

Abstract

Purpose: Skin-derived Precursor Schwann cells (SKP-SCs) have been reported to provide neuroprotection for the injured and dysmyelinated nervous system. However, little is known about SKP-SCs on acute ischemic stroke (AIS). We aimed to explore the efficacy and the potential mechanism of action of SKP-SCs on AIS in a rat ischemic stroke model.Methods: Adult male Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) for 1.5 h on Day 0 and subsequently received an intracarotid injection of 2 × 106 green fluorescent protein (GFP) -labeled SKP-SCs or phosphate buffered saline (PBS) during reperfusion. Neurological function was assessed by behavioral tests on Days 1, 4, 7, 14, and 28. In a satellite cohort, rat brains were harvested and infarct volume was measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining on Days 1 and 7, and migration and survival of SKP-SCs in the brain were traced by monitoring green fluorescence at 6 and12 h on Day 0, and on Days 1, 4, 7, 14, and 28. Histopathology and immunofluorescence staining were used to analyze the morphology, survival and apoptosis of neurons. Additionally, in an in vitro SKP-SC co-culture model using fetal rat primary cortical neurons underwent oxygen glucose deprivation/reoxygenation (OGD/R), Western blot was used to detect the expression of apoptosis indicators including activated caspase-3, Bax, and Bcl-2. TUNEL staining was used to count apoptotic cells.Results: Intracarotid transplantation of SKP-SCs effectively migrated to the periinfarct area and survived for at least 4 weeks. Transplanted SKP-SCs inhibited neuronal apoptosis, reduced infarct volume, and improved neurological recovery in the MCAO rats. Moreover, in vitro data showed that SKP-SCs treatment inhibited OGD/R-induced neuronal apoptosis and promoted survival of the cultured primary cortical neurons.Conclusions: Intracarotid transplantation of SKP-SCs promoted functional recovery in the rat AIS model and possesses the potential to be further developed as a novel therapy to treat ischemic stroke in humans.

Recent progresses in novel in vitro models of primary neurons: A biomaterial perspective

“…The function of BBB can be restored by optimizing the type, proportion, and distribution of cells. In addition, Transwell cultures offer valuable cues for the interaction between primary neurons and glial cells in mechanical injury, ischemic stroke, and other pathological conditions ( Liang et al, 2021 ; Lorenzen et al, 2021 ). The porous polymeric membrane structure was also utilized to study novel cell–cell interaction modalities, such as extracellular vesicles and small RNA-based intercellular crosstalk ( Mao M. et al, 2020 ).…”

Skin precursor‐derived Schwann cells accelerate in vivo prevascularization of tissue‐engineered nerves to promote peripheral nerve regeneration

“…Given that support cells secrete a variety of cytokines, we hypothesized that stem cells or their differentiated cells may play a positive role in prevascularization well. Skin precursor‐derived Schwann cells (SKP‐SCs), an ideal candidate in neural tissue engineering, were considered for in vivo prevascularization of tissue‐engineered nerves in a shorter period (Liang et al, 2021; Wu et al, 2020). If the prevascularization and support cells are integrated, could the vascular factors and cellular factors that promote nerve regeneration play a dual role?…”