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Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery

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Neural Regeneration Research 2022年第8期17卷 1814-1820页

作者： Kun Zhang Wen-Can Lu Ming Zhang Qian Zhang Pan-Pan Xian Fang-Fang Liu Zhi-Yang Chen Chung Sookja Kim Sheng-Xi Wu Hui-Ren Tao Ya-Zhou Wang Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Tongji UniversityShanghaiChina Department of Spine Surgery Shenzhen University General HospitalShenzhenGuangdong ProvinceChina Department of Neurology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Department of Anesthesiology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Faculty of medicine Macao University of Science and TechnologyMacao Special Administrative RegionChina

Neural stem cell(NSC)transplantation is a promising strategy for replacing lost neurons following spinal cord ***,the survival and differentiation of transplanted NSCs is limited,possibly owing to the neurotoxic inflammatory *** of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages,we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase(AR),a key enzyme in the polyol pathway of glucose metabolism,would provide a more beneficial microenvironment for NSC survival and ***,we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries.M2 macrophages promoted the differentiation of NSCs into neurons in *** of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional *** findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

关键词： aldose reductase functional recovery inflammation macrophage microglia neural stem cell transplantation neuronal differentiation polarization spinal cord injury

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