title: Immunotherapeutic effects of lymphocytes co-cultured with human cord blood-derived multipotent stem cells transplantation on APP/PS1 mice.
abstract: Alzheimer's disease (AD) is an inexorable neurodegenerative disease that involves neuroinflammation in the brain, in addition to abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. Evidence shows that human cord blood-derived multipotent stem cells (CB-SCs) can modulate autoimmune responses by altering regulatory T cells (Tregs). Our previous study found that CB-SCs could regulate the peripheral immune system of AD patients in vitro, mainly increasing the proportion of Tregs and anti-inflammatory cytokines. To further investigate the effects of lymphocytes co-cultured with CB-SCs on AD, the APP/PS1 mice received monthly transplants of lymphocytes co-cultured with CB-SCs for 4 months. Then, the ethological and biochemical experiments were conducted. We found that APP/PS1 mice injected with lymphocytes co-cultured with CB-SCs showed improved spatial learning, which significantly correlated with fewer Aβ plaques in brain. The present study also indicated that lymphocytes co-cultured with CB-SCs could promote the protective and reparative cytokines in the peripheral blood and brain to alleviate neuroinflammation in AD mice. These findings conclude that the systemic transplantation of lymphocytes co-cultured with CB-SCs can improve cognitive and pathological impairment of APP/PS1 mice via an immunomodulatory effect.
authors.affiliation: School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Guitao
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Xiaosan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Tianrui
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China. Electronic address: Xiaohong-Li@sdu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000502:physiology / Q000637:transplantation; D053764:Presenilin-1 / Q000378:metabolism; D065853:Spatial Learning / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D016207:Cytokines; D008840:Microfilament Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053773:Transforming Growth Factor beta1
keywords: Alzheimer’s disease; Cord blood-derived multipotent stem cells; Immunotherapy; Inflammation; Lymphocytes