Adipose tissue-derived stem cells rescue Purkinje neurons and alleviate inflammatory responses in Niemann-Pick disease type C mice.
Adult stem cells offer special therapeutic prospects because they can be isolated for autologous transplantation, expanded ex vivo, and differentiated into various cell types. We previously reported that bone marrow-derived mesenchymal stem cells improve neurological deficits in neurodegenerative disease animal models. However, the efficacy of adipose tissue-derived stem cells (ADSCs) transplantation in similar models remains unknown. Herein, we demonstrate that ADSCs, when transplanted into Niemann-Pick disease type C (NP-C) mouse cerebellum, elicit rescue of Purkinje neurons and restoration of motor coordination together with alleviation of inflammatory responses as verified by immunohistochemistry and real-time PCR using glial fibrillary acidic protein (GFAP), F4/80, IL-1 beta, IL-6, and TNF-alpha. Most importantly, ADSCs enhance electrically active Purkinje neurons with functional synaptic formation after transplantation in NP-C disease model mice. This report demonstrates for the first time that ADSCs can rescue imperiled Purkinje neurons and alleviate the inflammatory response in NP-C disease model mice, thereby signifying the therapeutic potential of ADSCs for neurodegenerative diseases.
Bae
Jae-sung
JS
Department of Physiology, Cell and Matrix Research Institute, BSEI, World Class University Program, School of Medicine, Kyungpook National University, Daegu, Korea. jsbae@knu.ac.kr
Carter
Janet E
JE
Jin
Hee Kyung
HK
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002470:Cell Survival; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D005434:Flow Cytometry; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D052556:Niemann-Pick Disease, Type C / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology*; D013109:Sphingomyelins / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
D013109:Sphingomyelins; D002784:Cholesterol