Improvement of Neurological Function in Rats with Ischemic Stroke by Adipose-derived Pericytes

Abstract

Pericytes possess high multipotent features and cell plasticity, and produce angiogenic and neurotrophic factors that indicate their high regenerative potential. The aim of this study was to investigate whether transplantation of adipose-derived pericytes can improve functional recovery and neurovascular plasticity after ischemic stroke in rats. Rat adipose-derived pericytes were isolated from subcutaneous adipose tissue by fluorescence-activated cell sorting. Adult male Wistar rats were subjected to 90 min of middle cerebral artery occlusion followed by intravenous injection of rat adipose-derived pericytes 24 h later. Functional recovery evaluations were performed at 1, 7, 14, and 28 days after injection of rat adipose-derived pericytes. Angiogenesis and neurogenesis were examined in rat brains using immunohistochemistry. It was observed that intravenous injection of adipose-derived pericytes significantly improved recovery of neurological function in rats with stroke compared to phosphate-buffered saline–treated controls. Immunohistochemical analysis revealed that the number of blood capillaries was significantly increased along the ischemic boundary zone of the cortex and striatum in stroke rats treated with adipose-derived pericytes. In addition, treatment with adipose-derived pericytes increased the number of doublecortin positive neuroblasts. Our data suggest that transplantation of adipose-derived pericytes can significantly improve the neurologic status and contribute to neurovascular remodeling in rats after ischemic stroke. These data provide a new insight for future cell therapies that aim to treat ischemic stroke patients.

Peri(vascular)cytes identity in the brain

“…Depending on tissue and environmental cues, pericytes can differentiate into other specialized cells, such as osteoprogenitor cells (Supakul et al, 2019) or adipocytes (Alexander et al, 2016). This versatility, similar to that of stem cells, raised the question whether these cells are bona fide mesenchymal stem cells (Crisan et al, 2008), a concept which has been widely embraced, up to the point that pericytes were considered a source for cell transplantation in regenerative therapies (Crisan et al, 2012;Karow, 2013;Vezzani et al, 2018;Supakul et al, 2019), including following CNS pathological states such as stroke (Caporarello et al, 2019;Ogay et al, 2020).…”

Vascular Biology

“…17 Functional recovery after stroke is attenuated in pericyte-deficient mice, due to loss of reciprocal interaction between pericytes and macrophages. 18 Transplantation of hematopoietic stem cell- 19 and adipose-derived pericytes 20 promote recovery after experimental stroke. Exposure of pericytes to PGE2 (prostaglandin E2) causes their detachment from capillaries, 21 which permits endothelial cell sprouting during vascular remodeling.…”