title: Human umbilical cord blood-derived mesenchymal stem cells improve neurological abnormalities of Niemann-Pick type C mouse by modulation of neuroinflammatory condition.
abstract: Niemann-Pick type C (NP-C) disease is a devastating developmental disorder with progressive and fatal neurodegeneration. We have used a mouse model of Niemann-Pick type C (NP-C) disease to evaluate the effects of direct intracerebral transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on the progression of neurological disease in this order. Here, we show that hUCB-MSCs transplantation into NP-C mice prevents the loss of Purkinje neurons and inhibits cerebellar apoptotic cell death. Interestingly, these effects were associated with the modulation of inflammatory responses, as evidenced by increased anti-inflammatory cytokine IL-10, and reduced abnormal astrocytic activation. Furthermore, our results show that the hUCB-MSCs transplantation reduced the cholesterol accumulation level in neurons in NP-C mice compared with sham-transplanted animals. This study provides the first evidence that hUCB-MSCs can improve neurological symptoms in NP-C disease, suggesting it as a potential therapeutic agent against neurodegenerative diseases.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Bae
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods; D017931:DNA Primers; D036861:Delivery, Obstetric; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000209:etiology / Q000601:surgery / Q000662:veterinary*; D007378:Interleukins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000150:complications / Q000503:physiopathology / Q000601:surgery / Q000662:veterinary*; D011247:Pregnancy; D045442:Rotarod Performance Test; D016212:Transforming Growth Factor beta / Q000235:genetics; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D016212:Transforming Growth Factor beta