title: Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats With Neonatal Hypoxic-Ischemic Encephalopathy.
abstract: Improving the effects of human adipose tissue-derived mesenchymal stem cells (ASCs) on the demyelination and neurobehavioral function was investigated in an experimental model of neonatal hypoxic-ischemic encephalopathy (HIE). Seven-day-old male rats were subjected to hypoxia-ischemia-lipopolysaccharide and intracerebroventricularly transplanted with human ASCs (4 × 10(5) cells/rat) once at postnatal day 10 (PND10) or repeatedly at PND10, 17, 27, and 37. Neurobehavioral abnormalities (at PND20, 30, and 40) and cognitive functions (at PND41-44) were evaluated using multiple test systems. Human ASCs recovered the using ratio of forelimb contralateral to the injured brain, improved locomotor activity, and restored rota-rod performance of HIE animals, in addition to showing a marked improvement of cognitive functions. It was confirmed that transplanted human ASCs migrated to injured areas and differentiated into oligodendrocytes expressing myelin basic protein (MBP). Moreover, transplanted ASCs restored production of growth and neurotrophic factors and expression of decreased inflammatory cytokines, leading to attenuation of host MBP loss. The results indicate that transplanted ASCs restored neurobehavioral functions by producing MBP as well as by preserving host myelins, which might be mediated by ASCs' anti-inflammatory activity and release of growth and neurotrophic factors.
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Dongsun
authors: D
authors: Park
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Sun Hee
authors: SH
authors: Lee
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Dae Kwon
authors: DK
authors: Bae
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Yun-Hui
authors: YH
authors: Yang
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Goeun
authors: G
authors: Yang
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Jangbeen
authors: J
authors: Kyung
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Dajeong
authors: D
authors: Kim
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Ehn-Kyoung
authors: EK
authors: Choi
authors: † College of Pharmacy, Chungbuk National University , Cheongju , Republic of Korea.
authors: Jin Tae
authors: JT
authors: Hong
authors: ‡ Stem Cell Research Center, RNL BIO Co., Ltd. , Seoul , Republic of Korea.
authors: Il Seob
authors: IS
authors: Shin
authors: ‡ Stem Cell Research Center, RNL BIO Co., Ltd. , Seoul , Republic of Korea.
authors: Sung Keun
authors: SK
authors: Kang
authors: ‡ Stem Cell Research Center, RNL BIO Co., Ltd. , Seoul , Republic of Korea.
authors: Jeong Chan
authors: JC
authors: Ra
authors: College of Veterinary Medicine, Chungbuk National University , Cheongju , Republic of Korea.
authors: Yun-Bae
authors: YB
authors: Kim
keywords: Adipose tissue-derived mesenchymal stem cell (ASC); Anti-inflammation; Cognition; Differentiation; Growth/neurotrophic factor; Neonatal hypoxic-ischemic encephalopathy (HIE); Neurobehavior