中国学者《Stem Cell》超越一个世纪的干细胞成果

　　

生物通报道，来自美国康涅狄格大学医学院免疫系、干细胞研究所、遗传与发育生物学系；中国北京大学附属人民医院以及长沙湘雅医院的科学家们在干细胞研究方面取得新进展，成果文章Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Response against Colon Cancer 发表在最新一期的《Stem Cell》上，中国科学家们发现了人类干细胞具有提供结肠癌疫苗的潜力。

 

文章通讯作者是来自美国康涅狄格大学医学院的免疫学专家Bei Liu 博士和 Zihai Li博士。

 

这项发现是建立在具有一个世纪的历史理论之上的，即用胚胎物质进行免疫接种可能产生一种抗肿瘤应答。然而，这种理论从未超出过动物研究，因此这项关于人类干细胞可以用于预防结肠癌的免疫接种的发现既新颖又令人意外。

 

Zihai Li博士表示，这一新的发现可能为癌症疫苗研究开辟一个全新的天地。癌细胞和干细胞拥有许多同样的分子和生物学特征。通过用干细胞为宿主接种，我们有能力‘欺骗’免疫系统认为癌细胞存在，因此也就启动了一个抗癌免疫程序。

 

该研究是首个涉及人类干细胞在预防结肠癌的免疫接种方面的研究，而且代表了Zihai Li博士与干细胞专家Renhe Xu在康涅狄格大学干细胞研究所的著名实验室之间的合作。

 

这个研究组用人类胚胎干细胞（hES）为实验小鼠进行免疫接种，并发现了针对结肠癌的持续的免疫应答。该研究组见到了接受免疫的小鼠的肿瘤生长显著减少。这显示了接受免疫接种的小鼠可能通过应用hES细胞从而产生强有力的抗肿瘤应答。

 

该研究组还发现，尽管天然的胚胎干细胞有能力产生应答，人造的诱导多能干细胞（iPSC）却不能。这很重要，因为它挑战了一种理论，即iPSC 和hES一样而且可能在干细胞研究的前沿领域代替后者。

 

Bei Liu博士预见性地表示，尽管我们仅仅测试了对结肠癌的保护作用，我们认为干细胞可能有助于产生广谱抗癌免疫应答，因此可以作为一种通用的癌症疫苗。

 

（生物通 小茜）

生物通推荐原文检索

Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Response against Colon Cancer

Yi Li 1 4, Hui Zeng 2 3 5, Ren-He Xu 2 3, Bei Liu 1 2 *, Zihai Li 1 2 *

1Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030-1601

2UConn Stem Cell Institute, University of Connecticut School of Medicine, Farmington, CT 06030-1601

3Department of Genetics and Developmental Biology, University of Connecticut School of Medicine, Farmington, CT 06030-1601

4Department of Gynecology and Obstetrics, Peking University People's Hospital, 100044 Beijing, China

5Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan 410008, China

 

*Correspondence to Bei Liu, Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA

*Correspondence to Zihai Li, Department of Immunology, MC 1601, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA

 

Funded by:

Connecticut Stem Cell Research Grants Program; Grant Number: 06SCA031, 06SCD02

 

Keywords

Embryonic stem cells • induced pluripotent stem cells • cancer vaccine • oncofetal antigen • myeloid derived suppressor cells

 

【Abstract】

The history of immunizing with embryonic materials to generate an anti-tumor immune response dates back a century ago. The premise is that cancer cells share the expression of oncofetal antigens with embryonic materials and that the immune response against these antigens in the embryonic tissues is cross-protective against cancer. However, such a practice has never advanced beyond experimental animal settings, due to lack of uniformed source tissues and ethical challenges. With the availability of well-characterized human pluripotent stem cells, it is now possible to ask if tumor protective immunity could indeed be elicited with stem cells. Herein, we investigated if vaccination with defined human embryonic stem (hES) or induced pluripotent stem (iPS) cells was effective against a colon carcinoma. We discovered that vaccination of mice with hES cell line H9 generated consistent cellular and humoral immune responses against CT26 colon carcinoma. Protection correlated strongly with the expansion of tumor-responsive and interferon -producing cells and the profound loss of CD11b+Gr-1+ myeloid derived suppressor cells in the spleen. No evidence of autoimmunity was observed. We also compared the immunogenicity against colon cancer between a hES cell line CT2 and an iPS cell line TZ1 that were generated in the same stem cell facility. We found that the iPS cell line was inferior to the hES cell line in conferring tumor protection, suggesting that there is heterogeneity of expression of oncofetal antigens by hES and iPS cells. We conclude that the hES-based vaccine is a promising modality for immunotherapy of cancer.