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1.
Transpl Immunol ; 75: 101701, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36038047

RESUMO

Earlier published research showed that cord blood-derived multipotent stem cells (CB-SCs) exhibited the intrinsic expression of specific transcription factors (e.g., En1, Nurr1 and Wnt1) and seems to be induced to form dopamine neurons in vitro. In this research, we further investigated the therapeutic potential of CB-SCs in 6-hydroxydopamine lesioned Parkinson's disease (PD) rats. The results of PCR analysis showed that CB-SCs could express transcription factors associated with pluripotentiality and dopaminergic differentiation (e.g., Klf4, c-Myc, Nanog, Sox2, Ngn2, and Nurr1). After being transplanted into the striatum and substantia nigra of PD rats, most of CB-SCs (>90%) developed a fate commitment to dopaminergic differentiation, expressed as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). The improvement effect of cell transplantation on dyskinesia in PD rats was better than that in sham control group. Moreover, higher levels of TH protein in brain homogenates further demonstrated that there were more surviving dopamine neurons in the brain of transplanted PD rats. Study concluds, CB SCS transplantation could promote the regeneration of dopamine neurons and behavioral recovery of PD rats.


Assuntos
Doença de Parkinson , Ratos , Humanos , Animais , Doença de Parkinson/terapia , Sangue Fetal/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/transplante , Células-Tronco Multipotentes/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Dopamina/metabolismo , Fatores de Transcrição , Modelos Animais de Doenças
2.
Behav Brain Res ; 315: 94-102, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27528555

RESUMO

Alzheimer's disease (AD) is an inexorable neurodegenerative disease that involves neuroinflammation in the brain, in addition to abnormal accumulation of amyloid-ß (Aß) 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 Aß 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.


Assuntos
Doença de Alzheimer/cirurgia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Linfócitos/fisiologia , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Sangue Fetal/citologia , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Células-Tronco Multipotentes/fisiologia , Células-Tronco Multipotentes/transplante , Presenilina-1/metabolismo , Aprendizagem Espacial/fisiologia , Fator de Crescimento Transformador beta1/metabolismo
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