Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.
Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.
复制标题
在裸鼠体内将脂肪干细胞转化为具有抗肿瘤活性的自然杀伤样细胞。
DOI：
10.1371/journal.pone.0106246
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lin CS
中科院分区：
文献类型：
--
作者：
Ning H;Lei HE;Xu YD;Guan RL;Venstrom JM;Lin G;Lue TF;Xin Z;Lin CS
外周血源性自然杀伤(NK)细胞的低丰度和组织不相容一直阻碍了将这些细胞开发成治疗产品的努力。另一方面，从胚胎干细胞(ESCs)和脐带血(UCB)等更丰富的细胞来源获得NK样细胞需要选择稀有的CD34+细胞。因此，我们试图将脂肪来源的干细胞(ADSCs)转化为NK样细胞。脂肪来源的干细胞数量丰富，天生就是CD34+。在造血诱导培养液中培养的ADSCs呈球状集落，表达CD34、CD45和KDR等造血标志物。在NK细胞特异性培养液中进一步诱导产生表达NK细胞标志物CD56的细胞群，因此被称为ADSC-NK。或者，在NK细胞特异的培养液中诱导之前，先用NK细胞特异性转录因子E4BP4转导造血诱导的ADSCs。后者的细胞群称为ADSC-NKE，表达CD56和其他NK细胞标记，如CD16、CD94、CD158、CD314、FasL和NKp46。ADSC-NKE对乳腺癌细胞MCF7、前列腺癌DU145、PC3、LNCaP、DuPro、C4-2和CWR22的杀伤作用与NK白血病细胞NKL相当，但对正常内皮细胞和平滑肌细胞无杀伤作用。在裸鼠实验中，ADSC-NKE能够显著延缓MCF7和PC3形成的肿瘤的进展。将ADSC-NKE注射到免疫活性大鼠体内，至少5周后在骨髓和脾中可检测到ADSC-NKE。综上所述，这些结果表明ADSCs可以转化为具有抗肿瘤活性的NK样细胞。
Efforts to develop peripheral blood-derived nature killer (NK) cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs) and umbilical cord blood (UCB) requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs), which are abundant and natively CD34+, into NK-like cells. When grown in hematopoietic induction medium, ADSCs formed sphere clusters and expressed hematopoietic markers CD34, CD45, and KDR. Further induction in NK cell-specific medium resulted in a population of cells that expressed NK cell marker CD56, and thus termed ADSC-NK. Alternatively, the hematopoietically induced ADSCs were transduced with NK cell-specific transcription factor E4BP4 prior to induction in NK cell-specific medium. This latter population of cells, termed ADSC-NKE, expressed CD56 and additional NK cell markers such as CD16, CD94, CD158, CD314, FasL, and NKp46. ADSC-NKE was as potent as NK leukemia cell NKL in killing breast cancer cell MCF7 and prostate cancer cells DU145, PC3, LnCap, DuPro, C4–2 and CWR22, but exhibited no killing activity toward normal endothelial and smooth muscle cells. In nude mice test ADSC-NKE was able to significantly delay the progression of tumors formed by MCF7 and PC3. When injected into immunocompetent rats, ADSC-NKE was detectable in bone marrow and spleen for at least 5 weeks. Together, these results suggest that ADSCs can be converted into NK-like cells with anti-tumor activities.
登录
查看更多内容
NFIL3/E4BP4是在体内开发和成熟所必需的。
DOI：
10.1084/jem.20092176
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kamizono S;Duncan GS;Seidel MG;Morimoto A;Hamada K;Grosveld G;Akashi K;Lind EF;Haight JP;Ohashi PS;Look AT;Mak TW
通讯作者：
Mak TW
影响因子：
11.4
作者：
Guimaraes, F;Guven, H;Dilber, MS
通讯作者：
Dilber, MS
影响因子：
2.6
作者：
Alici, Evren;Konstantinidis, Kyriakos V.;Dilber, M. Sirac
通讯作者：
Dilber, M. Sirac
影响因子：
4
作者：
Kao, I-Ting;Yao, Chao-Ling;Hwang, Shiaw-Min
通讯作者：
Hwang, Shiaw-Min
影响因子：
4.5
作者：
Lin, Guiting;Xin, Zhongcheng;Lin, Ching-Shwun
通讯作者：
Lin, Ching-Shwun