| 摘要: | 目前針對治療神經系統退化性疾病還是沒有非常有效之方法，例如急性腦中風目前是十大死亡原中之第二位，然而腦中風之主要原因為腦中不同部位之血管栓塞或硬化阻塞造成進而產生突發性肢體偏癱，失語，手腳麻木等不同程度之神經功能喪失，目前之治療方式在急性期施以抗凝血劑，抗血小板凝集劑，甚至血栓溶解劑之藥物治療，其他之慢性神經系統退化性疾病如巴金森病及杭丁頓舞蹈症，則以復健及其他預防性之保守療法為主，疾病之預後不佳，多半為行動不便須家人照料，造成社會及國家資源之耗損。腦中風造成神經細胞快速死亡，而死亡之神經細胞及血管肉皮細胞無法再生及修補因此神經功能便喪失，因此，近年來有許多學者研究在中風之動物身上植入外來之幹細胞（Stem cell），例如有骨髓中胚層幹細胞，臍帶血幹細胞甚至是胚胎幹細胞等，每位學者都發現不僅能讓中風鼠之神經功能部份回復；且植入之幹細胞可分化成神經細胞及血管內皮細胞，此種治療方式對未來腦中風及神經退化性疾病帶來一線曙光。在許多文獻中都證實在幹細胞可在體內或體外分化為成熟之細胞例如肌肉細胞、肝臟細胞及神經細胞等，因此在骨髓幹細胞及臍帶血幹細胞慢慢被大多數人注意且被大量的運用於治療相關疾病之際，慢慢發現因老年人之骨髓較不易培養出幹細胞，而臍帶血之幹細胞數量過少，故極需要尋找另一間質幹細胞之來源，然而胎盤組織可培養出很多代之間質幹細胞，因此可想而知的是對於治療神經系統退化性疾病應可提共一使神經細胞復原及再生的好方法之一。本研究將分三年進行。第二年之工作將已建立之成人胎盤間質幹細胞體外培養模式之後，利用胎盤間質幹細胞立體定位植入腦中風鼠腦中(中風七天後)，此後觀察老鼠每天之運動及感覺功能之恢復情況，期間以MRI 及MRS 觀察neuronal activity 恢復之情形，並於一個月後將實驗鼠之腦部取出，經切片染色觀察腦梗塞之大小，並以免疫化學染色之技術(TUNEL,MAP-2 and Neu-N)在顯微鏡下觀察腦梗塞周圍神經細胞受保護之情行及以Confocalmicroscopy 之技術檢視胎盤間質幹細胞之腦內分化之情形，藉以與對照組比較是否有統計上之意義。
Stem cells are clonogenic cells that have the capacity for self-renewal and multilineage differentiation. During embryogenesis, totipotent embryonic stem cells that are derived from the blastocyst give rise to ectoderm, mesoderm and endoderm lineage cell populations (Weissman, 2000). It has become evident that stem cells persist in adult tissues, although they represent a rare population localized in small niches (Woodbury et al., 2002). Adult stem cells are not totipotent, but they are capable of self-renewal and differentiation into multiple specialized cell types (Kopen et al., 1999). In tissues from postnatal animals, stem cells have been successfully isolated from liver, intestine, bone marrow and brain (Wei et al., 2000). Neural precursors that differentiate into neurons, astrocytes and oligodendrocytes may hold significant therapeutic potential for the replacement of damaged or diseased neural tissue resulting from congenital neuropathological conditions, brain injuries and neurodegenerative disorders. Although regional neurogenesis continues throughout the lifespan of rodents and humans, the number and availability of neural stem cells (NSCs) is limited in the postnatal central nervous system (CNS) (Barami et al., 2001; Shetty and Turner, 1996). The transplantation of NSCs has been shown to provide functional improvement in vivo (Barami et al., 2001; Borlongan et al., 1997; Masada et al., 1997; Shetty and Turner, 1996). Recent evidence indicates that bone marrow stem cell transplantation effectively prevented the progression of neurological disease signs in some functional studies, if it is performed at an early stage in the disease (Jin et al., 2002). Subpopulations of bone marrow cells may serve as an alternative source of stem cells for the treatment of CNS disease, whereby mesenchymal stem cells differentiate into various lineages of brain cells. It has been shown that cells isolated from both bone marrow and umbilical cord blood (CB) can give rise to neural cells in vitro (Black and Woodbury, 2001; Kohyama et al., 2001; Reyes and Verfaillie, 2001; Deng et al., 2001; Sanchez-Ramos et al., 2000; Sanchez-Ramos et al., 2001; Woodbury et al., 2000; Colter et al., 2000; Colter et al., 2001) and in vivo (Azizi et al., 1998; Kopen et al., 1999; Mezey et al., 2000; Brazelton et al., 2000). Many studies have shown that bone marrow-derived cells can give rise to neural cells as well as many tissue-specific cell phenotypes, including hematopoietic, skeletal muscle, hepatic, heart and vascular endothelial cells (Terskikh et al., 2001; Gussoni et al., 1999; Petersen et al., 1999). The results of these studies have shown that host tissue-specific microenvironment conditions may be essential for the multilineage transdifferentiation of bone marrow-derived stem cells (BMSCs). |
