| 摘要: | 缺血性心臟病與神經退化性疾病發生率隨年齡增加而增加。 當組織受 損時,由於心肌細胞及神經細胞具較弱的再生能力,因此自我修復損傷區 域是非常困難的。 近年,幹細胞治療提供缺血性心臟病及神經退化性疾病 新的治療策略。 幹細胞藉由自我更新,分化與旁分泌作用等能力,修復和 改善受損組織。 幹細胞治療方面,常用分離自初始器官或組織的人類間質 幹細胞。 然而,為了達到治療需求量,間質幹細胞在體外培養會面臨複製 時造成的細胞衰老。 這限制自體移植的幹細胞數量。 再者,缺血性與神 經退化疾病發生率隨年齡增加,病人年齡過大,降低了自體間質幹細胞治 療效率。 因此改變幹細胞來源是非常需要‧新的間質幹細胞來源可以來自 胎兒時期組織或是多功能性幹細胞。 依照細胞特性的不同,我們分別探討 胎盤幹細胞(一種源自胎兒時期幹細胞)用於缺血性心臟病及多功能性間質 幹細胞用於神經退化疾病的治療。 我們發現胎盤幹細胞能透過旁分泌作 用,促進心肌細胞存活及降低細胞凋亡。 更進一步發現,藉由調節體外培 養環境,可以加強幹細胞旁分泌作用。 在另一方面,我們也發現源自多功 能性之間質幹細胞,利用細胞骨架重組作用,可以更進一步往神經分化途 徑。 透過我們的發現,胎盤幹細胞及源自多功能性間質幹細胞可提供缺血 性心臟病及神經退化性疾病細胞治療上,新的幹細胞來源。;The incidences of ischemic heart disease (IHD) and neurodegenerative disease increase with age. When tissue injury occurs, cardiomyocytes and neural cells are unable to undergo repair due to poor regenerative capacity. In recent years, stem cell therapy appears to provide a new therapeutic strategy for both IHD and neurodegenerative diseases. Recipient-derived stem cells have been shown to repair and improve damaged tissue through many modalities, including self-renewal, differentiation, and paracrine effects. Human mesenchymal stem cells (MSCs) are an attractive stem cell type, which have been isolated from many adult organs and tissues. However, these adult MSCs undergo replicative senescence during in vitro expansion to reach the cell volumes needed for therapeutic use. This especially limits the number of autologous stem cells, which are usually isolated from older adult patients. Moreover, the incidence of ischemic and degenerative diseases increase with age, thus the use of any type of autologous adult MSCs would lose efficacy as the patient ages. Hence, alternative sources of MSCs are likely necessary. New sources of highly renewable MSCs can be derived from fetal-stage tissue (F) and pluripotent stem cells (PSCs). We therefore explored the application of F- MSCs on IHD, as well as MSCs derived from human PSCs, including human embryonic stem cells (ES) and induced pluripotent stem cells (iPS), on neurodegenerative diseases. Our results showed that PDMCs could promote survival and decrease apoptosis in cardiomyocytes through the paracrine function of secreted factors. Furthermore, these paracrine functions could be enhanced by modulation of extracellular matrix proteins. On the other hand, we also found that PSC-derived MSCs (PSC-MSCs) had potent capacity to undergo more committed neural differentiation through standard neural differentiation in conjunction with cytoskeletal rearrangement. Our findings give support to the use of PDMCs and PSC-MSCs as possible candidate stem cells for therapeutic application towards the respective areas of IHD and neurodegenerative disease. |
