Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Cytotherapy. 2012 May;14(5):630-8. doi: 10.3109/14653249.2012.663485. Epub 2012 Mar 12.
Niemann-Pick disease type C1 (NPC) is an autosomal recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly and progressive neurodegeneration. Thus far, studies of NPC mice have been performed mainly to study the brain and neurodegeneration, because degeneration in the brain was known as the primary cause of death in NPC mice. However, NPC is a systemic disease; therefore the purpose of this study was to find the possibility of a general therapeutic effect by applying and tracking transplanted human amniotic epithelial stem cells (hAESC) in NPC mice.
hAESC were administered to NPC homozygous (NPC(-/-)) mice via intravenous injection from 5 weeks of age; each recipient received 5 × 10(5) cells every other week. The body weight of each of the mice was measured every week, and the survival and state of each mouse was evaluated every day. The weight of the organs was measured, and serum chemistry, histology and the intensity of Filipin staining were evaluated.
The effect of cell transplantation was to extend the life span and reduce the rapid loss of weight. Moreover, alleviation of tissue damage was observed more in hAESC-treated NPC(-/-) mice than in non-treated NPC(-/-) mice. Cholesterol deposition was reduced after transplantation, and the relative weight of the liver was also decreased.
These data show that hAESC could delay the degeneration caused by fatal genetic disorders such as NPC. This study presents the prospect of relief of precipitous disease progression and the therapeutic possibility of applying hAESC to fatal genetic disorders.
尼曼-匹克病 C1 型（NPC）是一种常染色体隐性胆固醇贮积症，其特征为肝功能障碍、肝脾肿大和进行性神经退行性变。迄今为止，对 NPC 小鼠的研究主要是为了研究大脑和神经退行性变，因为已知脑退行性变是 NPC 小鼠死亡的主要原因。然而，NPC 是一种全身性疾病；因此，本研究的目的是通过对 NPC 纯合子（NPC（-/-））小鼠应用和跟踪移植的人羊膜上皮干细胞（hAESC）来寻找普遍治疗效果的可能性。
hAESC 通过静脉注射给予 5 周龄的 NPC 纯合子（NPC（-/-））小鼠；每个受体每两周接受 5×10（5）个细胞。每周测量每只小鼠的体重，并每天评估每只小鼠的存活和状态。测量器官重量，并评估血清化学、组织学和 Filipin 染色强度。
细胞移植的效果是延长寿命和减少体重的快速丧失。此外，与未治疗的 NPC（-/-）小鼠相比，在 hAESC 治疗的 NPC（-/-）小鼠中观察到组织损伤的缓解更为明显。移植后胆固醇沉积减少，肝的相对重量也降低。
这些数据表明，hAESC 可延缓致命遗传疾病（如 NPC）引起的退行性变。本研究提出了缓解急剧疾病进展的前景，并提出了将 hAESC 应用于致命遗传疾病的治疗可能性。
