干細(xì)胞干細(xì)胞(stem cell)干細(xì)胞干細(xì)胞(stem cell) 干細(xì)胞是具有自我干細(xì)胞是具有自我更新與分化潛能的未分更新與分化潛能的未分化或低分化細(xì)胞化或低分化細(xì)胞醫(yī)學(xué)界稱之為“萬用細(xì)胞”干細(xì)胞具有“無限” 的增殖能力，能夠產(chǎn)生與母代細(xì)胞相同的子代細(xì)胞，維持該干細(xì)胞種群 自我更新分化潛能 干細(xì)胞能分化生成不同表型的成熟細(xì)胞，例如胚胎干細(xì)胞可以分化形成個體的所有成熟細(xì)胞類型根據(jù)其發(fā)育階段不同，可分為：?胚胎干細(xì)胞胚胎干細(xì)胞 (ESC)(ESC)具有分化為機體具有分化為機體任何一種組織器官的潛能任何一種組織器官的潛能 如囊胚期內(nèi)細(xì)胞團(tuán)中的細(xì)胞如囊胚期內(nèi)細(xì)胞團(tuán)中的細(xì)胞?成體干細(xì)胞（成體干細(xì)胞（ASC)機體組織中保留的一部機體組織中保留的一部分比較原始的細(xì)胞分比較原始的細(xì)胞,一旦機體需要一旦機體需要,這些細(xì)這些細(xì)胞便可按發(fā)育途徑胞便可按發(fā)育途徑,先分裂后分化先分裂后分化,產(chǎn)生分產(chǎn)生分化細(xì)胞化細(xì)胞按分化潛能的大小全能干細(xì)胞全能干細(xì)胞：： 在在一一定定條條件件下下，，能能夠夠分分化化發(fā)發(fā)育育成成為為完完整整個個體體的的細(xì)細(xì)胞胞，，如如哺乳動物桑葚胚的哺乳動物桑葚胚的8 8細(xì)胞期之前的細(xì)胞細(xì)胞期之前的細(xì)胞 。

多能干細(xì)胞多能干細(xì)胞：：? 在胚胎發(fā)育的三胚層形成后，細(xì)胞的分化潛能受到在胚胎發(fā)育的三胚層形成后，細(xì)胞的分化潛能受到限制，僅能向本胚層組織和器官方向分化發(fā)育如造血多限制，僅能向本胚層組織和器官方向分化發(fā)育如造血多能干細(xì)胞能干細(xì)胞 單能干細(xì)胞單能干細(xì)胞: :只能分化為一種類型的細(xì)胞，而且自我更新能只能分化為一種類型的細(xì)胞，而且自我更新能力有限，如上皮組織基底層的干細(xì)胞，肌肉中的成肌細(xì)胞，力有限，如上皮組織基底層的干細(xì)胞，肌肉中的成肌細(xì)胞，紅系干細(xì)胞等紅系干細(xì)胞等骨髓干細(xì)胞?一類是造血干細(xì)胞（hematopoietic stem cells，HSCs），它為循環(huán)血液提供前體細(xì)胞；?另一類是間充質(zhì)干細(xì)胞（mesenchymal stem cells，MSCs），它是骨髓中主要的 支持細(xì)胞，在調(diào)節(jié)造血干細(xì)胞的長期存活，生長分化中起重要作用二、干細(xì)胞的生物學(xué)特征干細(xì)胞的生物學(xué)特征 （一） 具有“無限”的自我更新能力 （二）多向分化潛能（三）具有未分化或低分化特性 (四) 可塑性?干細(xì)胞干細(xì)胞終末分終末分化細(xì)胞化細(xì)胞1、干細(xì)胞的獨特增殖方式 干細(xì)胞通過干細(xì)胞通過非對非對稱分裂稱分裂產(chǎn)生與一個與產(chǎn)生與一個與母代細(xì)胞完全相同的母代細(xì)胞完全相同的子代細(xì)胞，以保持干子代細(xì)胞，以保持干細(xì)胞穩(wěn)定；同時還產(chǎn)細(xì)胞穩(wěn)定；同時還產(chǎn)生分化細(xì)胞。

生分化細(xì)胞2.2.細(xì)胞細(xì)胞分化分化的潛能隨個體發(fā)育進(jìn)的潛能隨個體發(fā)育進(jìn) 程逐漸程逐漸“縮窄縮窄”細(xì)細(xì)胞胞分分化化的的一一般般規(guī)規(guī)律律：：在在胚胚胎胎發(fā)發(fā)育育過過程程中中，，細(xì)細(xì)胞胞逐逐漸漸由由““全全能能””到到““多多能能””，，最后向最后向““單能單能””的趨向 干細(xì)胞的可塑性?干細(xì)胞的可塑性：即干細(xì)胞具有在不同微環(huán)境中可轉(zhuǎn)化為不同干細(xì)胞及不同類型的成熟組織細(xì)胞的特性?機制：1, 橫向分化? 2，去分化/脫分化 3，干細(xì)胞的異質(zhì)性 4，細(xì)胞融合 5，基因重組學(xué)說 6，亞全能干細(xì)胞學(xué)說影響因素：微環(huán)境和基因表達(dá)1 胚胎干細(xì)胞成體干細(xì)胞來源囊胚的內(nèi)細(xì)胞團(tuán)或胎兒的生殖脊成體的各種組織優(yōu)點易分離，純化，可無限增殖，有分化全能性可定向分化，不引起免疫排斥反應(yīng)，沒有倫理道德壓力缺點可自動分化形成畸胎瘤，可能引起免疫排斥反應(yīng)，有倫理道德壓力數(shù)量少，無特有的細(xì)胞表面標(biāo)志，難分離，難純化三 鑒定，篩選? ESC:胚胎細(xì)胞在發(fā)育的不同階段, 其細(xì)胞表面出現(xiàn)不同的抗原。

未分化的人ESC 細(xì)胞表面SSEA-3、SSEA-4、TI-1-60、TRA-1-81等呈陽性.這些標(biāo)記物加上干細(xì)胞時期細(xì)胞內(nèi)堿性磷酸酶、端粒酶的特異性高表達(dá), 可成為鑒定胚胎干細(xì)胞的依 據(jù).?ASC的鑒定識別主要通過三種途徑: 分離培養(yǎng)和形態(tài)學(xué)觀察; 免疫表型鑒定; 分化功能檢測四 干細(xì)胞的應(yīng)用?一，干細(xì)胞是早期胚胎發(fā)育的良好模型?二，干細(xì)胞是研究人類疾病的良好模型?三，干細(xì)胞具有臨床應(yīng)用的前景?1，移植治療?2，基因治療??3，轉(zhuǎn)運載體?4，干細(xì)胞庫五 存在的問題 1)干細(xì)胞的分離、純化、增殖、鑒定的問題 2)干細(xì)胞誘導(dǎo)分化的問題 3）移植時機的把握 4）供體細(xì)胞的功能表達(dá)問題 5)移植后免疫排斥反應(yīng) 6) 干細(xì)胞治療中生物安全，倫理和法律問題骨髓干細(xì)胞在抗肝纖維化治療中的應(yīng)用研究?優(yōu)點：1，近年來有不少文獻(xiàn)報道，骨髓干細(xì)胞可以分化為肝細(xì)胞，改善肝功能?2，研究發(fā)現(xiàn)，將肝星狀細(xì)胞與MSC 共培養(yǎng)后，受活性肝星狀細(xì)胞分泌的IL- 6 刺激，MSC 分泌IL- 10、TNF-α 和肝細(xì)胞生長因子（hepatocyte growth factor，HGF），使得肝星狀細(xì)胞增殖激活明顯受抑制，凋亡增加，膠原合成顯著減少。

3，相關(guān)資料顯示，MSCs 除了有可以分化為肝細(xì)胞的潛能外，還可以通過表達(dá)高水平的MMPs，尤其是MMP- 9來減少肝臟細(xì)胞外基質(zhì)的沉積?弊端：1，最近研究顯示，BMSCs 移植入肝硬化小鼠體內(nèi)，骨髓源性肝細(xì)胞僅占肝組織細(xì)胞總數(shù)的0.6%，而骨髓源性肝星狀細(xì)胞和肌成纖維細(xì)胞則分別高達(dá)68%和70%，且是通過非融合方式直接來源于BMSCs，并具有Ⅰ型膠原轉(zhuǎn)錄活性，能促進(jìn)纖維變性反應(yīng)?2，另外，也有學(xué)者認(rèn)為，慢性肝損傷還可誘導(dǎo)BMSCs 分化為肌成纖維細(xì)胞的前體細(xì)胞———成纖維細(xì)胞，潛在地促進(jìn)肝纖維化發(fā)展因此用于肝再生的BMSCs 移植研究必須警惕其加重肝纖維化形成的可能?3，最值得引起注意的是骨髓干細(xì)胞可以促進(jìn)肝細(xì)胞性肝癌的發(fā)生The Therapeutic Potential of Human UmbilicalMesenchymal Stem Cells from Wharton’s Jellyin the Treatment of Rat Liver Fibrosis Pei-Chun Tsai,1 Tz-Win Fu,5 Yi-Ming Arthur Chen,2 Tsui-Ling Ko,8 Tien-Hua Chen,3 Yang-Hsin Shih,6,9 Shih-Chieh Hung,4,7* and Yu-Show Fu3,1Abstract?We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton’s jelly on carbon tetrachloride(CCl4)–induced liver fibrosis in rats.? Rats were treated with CCl4 for 4 weeks, and this was followed by a direct injection of HUMSCs into their livers. After 4 more weeks of CCl4 treatment (8 weeks in all), rats with HUMSC transplants [CCl4(8W) ＋HUMSC liver] exhibited a significant reduction in liver fibrosis, as evidenced by Sirius red staining and a collagen content assay, in comparison with rats treated with CCl4 for 8 weeks without HUMSC transplants [CCl4 (8W)]. ?Moreover, rats in theCCl4 (8W)HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, a-smooth muscle actin, and transforming growth factor-1 in the liver, whereas the expression of hepatic mesenchymal epithelial transition factor–phosphorylated type (Met-P) and hepatocyte growth factor was up-regulated, in comparison with the CCl4 (8W) group。

?Notably, engrafted HUMSCs scattered mostly in the hepatic connective tissue but did not differentiate into hepatocytes expressing human albumin or a -fetoprotein.? Instead, these engrafted, undifferentiated HUMSCs secreted a variety of bioactive cytokines that may restore liver function and promote regeneration. Human cytokine assay revealed that the amounts of human cutaneous T cell–attracting chemokine, leukemia inhibitory factor, and prolactin were substantially greater in the livers of the CCl4 (8W)HUMSC (liver) group, with considerably reduced hepatic inflammation manifested by a micro positron emission tomography scan.? Our findings suggest that xenogeneic transplantation of HUMSCs is a novel approach for treating liver fibrosis and may be a promising therapeutic intervention in the future.Aim?We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton’s jelly on carbon tetrachloride(CCl4)–induced liver fibrosis in rats.Materials and Methods Rat:1,normal 2, CCl4 for 8 weeks 3, CCl4(8W) ＋HUMSC index: weight, CTACK, Prolactin, LIF ,Met-P HGF/GAPGH GOT,GPT, a-SMA, TGF-β1, collagencollagen [18F]-FDG [18F]-FDG human albumin , human a-FP , fresh liver ResultsConclusions?1,HUMSC transplantation can increase1,HUMSC transplantation can increase CTACK, Prolactin, LIF ,Met-P ,HGF/GAPGH and reduce GOT,GPT, a-SMA, TGF-β1, inflammation so that it can inhibit HSC proliferation and collagen synthesis and enhance liver cell repair.?2, The effect of HUMSCs on reducing fibrogenesis most likely relies on bioactive factors or cytokines released from the grafted HUMSCs to trigger liver regeneration rather than on the differentiation of these cells into hepatocytes.?In conclusion, sufficient amounts of HUMSCs in rat livers can secrete cytokines, reduce the activation of hepatic stellate cells, enhance liver cell repair, and effectively cure liver fibrosis.Thank you??！。