Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment  

作　　者：Sumei Liu Baoguo Liu Qian Li Tianqi Zheng Bochao Liu Mo Li Zhiguo Chen 

机构地区：[1]Cell Therapy Center,Beijing Institute of Geriatrics,Xuanwu Hospital,Capital Medical University,National Clinical Research Center for Geriatric Diseases,and Key Laboratory of Neurodegenerative Diseases,Ministry of Education,Beijing,China [2]Center of Neural Injury and Repair,Beijing Institute for Brain Disorders,Beijing,China [3]Center of Parkinson’s Disease,Beijing Institute for Brain Disorders,Beijing,China

出　　处：《Neural Regeneration Research》2024年第2期440-446,共7页中国神经再生研究（英文版）

基　　金：supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC);the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC);the Natural Science Foundation of Beijing,No.5142005(to ZC);Beijing Talents Foundation,No.2017000021223TD03(to ZC);Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC);Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC);Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC);the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC);the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。

摘　　要：Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

关 键 词：biomaterial FIBRINOGEN functional recovery induced neural stem cell transplantation MICROENVIRONMENT MICROGLIA spinal cord injury THROMBIN 

分 类 号：R651.2[医药卫生—外科学]