Reversibly immortalized human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are responsive to BMP9-induced osteogenic and adipogenic differentiation

被引：41

作者：

Shu, Yi ^{[1
,2
,3
,4
,5
,6
,7
]}

Yang, Chao ^{[1
,2
,3
,4
,5
]}

Ji, Xiaojuan ^{[1
,2
,3
,4
,5
]}

Zhang, Linghuan ^{[1
,2
,3
,4
,5
]}

Bi, Yang ^{[1
,2
,3
,4
,5
]}

Yang, Ke ^{[1
,2
,3
,4
,5
,8
]}

Gong, Mengjia ^{[1
,2
,3
,4
]}

Liu, Xing ^{[1
,2
,3
,4
,5
]}

Guo, Qi ^{[9
]}

Su, Yuxi ^{[1
,2
,3
,4
,5
]}

Qu, Xiangyang ^{[1
,2
,3
,4
,5
]}

Nan, Guoxin ^{[1
,2
,3
,4
,5
]}

Zhao, Chen ^{[5
,6
,7
]}

Zeng, Zongyue ^{[5
,6
,7
]}

Yu, Xinyi ^{[5
,6
,7
]}

Zhang, Ruyi ^{[5
,6
,7
]}

Yan, Shujuan ^{[5
,6
,7
]}

Lei, Jiayan ^{[5
,6
,7
]}

Wu, Ke ^{[5
,6
,7
]}

Wu, Ying ^{[5
,10
]}

An, Liping ^{[5
,11
]}

Huang, Shifeng ^{[5
,6
,7
]}

Gong, Cheng ^{[5
,12
]}

Yuan, Chengfu ^{[5
,13
]}

Liu, Wei ^{[5
,6
,7
]}

Huang, Bo ^{[5
,6
,7
]}

Feng, Yixiao ^{[5
,6
,7
]}

Zhang, Bo ^{[5
,11
]}

Dai, Zhengyu ^{[5
,14
]}

Shen, Yi ^{[5
,15
]}

Luo, Wenping ^{[5
,6
,7
]}

Wang, Xi ^{[5
,6
,7
]}

Haydon, Rex C. ^{[5
]}

Luu, Hue H. ^{[5
]}

Reid, Russell R. ^{[5
,16
]}

Wolf, Jennifer Moriatis ^{[5
]}

Lee, Michael J. ^{[5
]}

He, Tong-Chuan ^{[1
,2
,3
,4
,5
,6
,7
]}

Li, Yasha ^{[1
,2
,3
,4
,5
]}

机构：

[1] Chongqing Med Univ, Stem Cell Biol & Therapy Lab, Key Lab Child Dev & Disorders, Childrens Hosp,Minist Educ, Chongqing 400014, Peoples R China

[2] Chongqing Med Univ, Childrens Hosp, Dept Pediat Surg, Chongqing, Peoples R China

[3] Chongqing Med Univ, Childrens Hosp, Dept Cardiol, Chongqing, Peoples R China

[4] Chongqing Med Univ, Childrens Hosp, Dept Orthopaed Surg, Chongqing, Peoples R China

[5] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Mol Oncol Lab, Chicago, IL 60637 USA

[6] Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med, Sch Lab Med, Chongqing, Peoples R China

[7] Chongqing Med Univ, Affiliated Hosp, Chongqing, Peoples R China

[8] Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing, Peoples R China

[9] Chongqing Qual Testing & Inspect Ctr Med Devices, Chongqing, Peoples R China

[10] Beijing Univ Chinese Med, Dept Immunol & Microbiol, Beijing, Peoples R China

[11] Lanzhou Univ, Key Lab Orthopaed Surg Gansu Prov, Dept Orthopaed Surg, Hosp 2, Lanzhou, Gansu, Peoples R China

[12] Wuhan Univ, Affiliated Zhongnan Hosp, Dept Surg, Wuhan, Hubei, Peoples R China

[13] China Three Gorges Univ, Sch Med, Dept Biochem & Mol Biol, Yichang, Peoples R China

[14] Chongqing Hosp Tradit Chinese Med, Dept Orthopaed Surg, Chongqing, Peoples R China

[15] Cent S Univ, Dept Orthopaed Surg, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[16] Univ Chicago, Med Ctr, Dept Surg, Lab Craniofacial Biol & Dev,Sect Plast Surg, Chicago, IL 60637 USA

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2018年 / 119卷 / 11期

基金：

美国国家卫生研究院;

关键词：

BMP9-induced osteogenic differentiation; immunotherapy; mesenchymal stem cells (MSCs); regenerative medicine; SV40 T antigen immortalization; umbilical cord-derived MSCs (UC-MSCs); PROTEIN; 9; BMP9; OSTEO/ODONTOBLASTIC DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; BONE-FORMATION; TUMOR-GROWTH; WNT; AMPLIFICATION; PROGENITORS; METASTASIS; GENERATION;

D O I：

10.1002/jcb.27140

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human mesenchymal stem cells (MSCs) are a heterogeneous subset of nonhematopoietic multipotent stromal stem cells and can differentiate into mesodermal lineage, such as adipocytes, osteocytes, and chondrocytes, as well as ectodermal and endodermal lineages. Human umbilical cord (UC) is one of the most promising sources of MSCs. However, the molecular and cellular characteristics of UC-derived MSCs (UC-MSCs) require extensive investigations, which are hampered by the limited lifespan and the diminished potency over passages. Here, we used the piggyBac transposon-based simian virus 40 T antigen (SV40T) immortalization system and effectively immortalized UC-MSCs, yielding the iUC-MSCs. A vast majority of the immortalized lines are positive for MSC markers but not for hematopoietic markers. The immortalization phenotype of the iUC-MSCs can be effectively reversed by flippase recombinase-induced the removal of SV40T antigen. While possessing long-term proliferation capability, the iUC-MSCs are not tumorigenic in vivo. Upon bone morphogenetic protein 9 (BMP9) stimulation, the iUC-MSC cells effectively differentiate into osteogenic, chondrogenic, and adipogenic lineages both in vitro and in vivo, which is indistinguishable from that of primary UC-MSCs, indicating that the immortalized UC-MSCs possess the characteristics similar to that of their primary counterparts and retain trilineage differentiation potential upon BMP9 stimulation. Therefore, the engineered iUC-MSCs should be a valuable alternative cell source for studying UC-MSC biology and their potential utilities in immunotherapies and regenerative medicine.

引用

页码：8872 / 8886

页数：15

共 49 条

[1]

Batsali AK, 2013, CURR STEM CELL RES T, V8, P144

[2] Functional Characteristics of Reversibly Immortalized Hepatic Progenitor Cells Derived from Mouse Embryonic Liver [J].

Bi, Yang ;

He, Yun ;

Huang, Jiayi ;

Su, Yuxi ;

Zhu, Gao-Hui ;

Wang, Yi ;

Qiao, Min ;

Zhang, Bing-Qiang ;

Zhang, Hongyu ;

Wang, Zhongliang ;

Liu, Wei ;

Cui, Jing ;

Kang, Quan ;

Zhang, Zhonglin ;

Deng, Youlin ;

Li, Ruifang ;

Zhang, Qian ;

Yang, Ke ;

Luu, Hue H. ;

Haydon, Rex C. ;

He, Tong-Chuan ;

Tang, Ni .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2014, 34 (04) :1318-1338

[3] Pre-activation of retinoid signaling facilitates neuronal differentiation of mesenchymal stem cells [J].

Bi, Yang ;

Gong, Min ;

Zhang, Xiaojuan ;

Zhang, Xuan ;

Jiang, Wei ;

Zhang, Yun ;

Chen, Jie ;

Liu, Youxue ;

He, Tong-Chuan ;

Li, Tingyu .

DEVELOPMENT GROWTH & DIFFERENTIATION, 2010, 52 (05) :419-431

[4] Wnt Antagonist SFRP3 Inhibits the Differentiation of Mouse Hepatic Progenitor Cells [J].

Bi, Yang ;

Huang, Jiayi ;

He, Yun ;

Zhu, Gao-Hui ;

Su, Yuxi ;

He, Bai-Cheng ;

Luo, Jinyong ;

Wang, Yi ;

Kang, Quan ;

Luo, Qing ;

Chen, Liang ;

Zuo, Guo-Wei ;

Jiang, Wei ;

Liu, Bo ;

Shi, Qiong ;

Tang, Min ;

Zhang, Bing-Qiang ;

Weng, Yaguang ;

Huang, Ailong ;

Zhou, Lan ;

Feng, Tao ;

Luu, Hue H. ;

Haydon, Rex C. ;

He, Tong-Chuan ;

Tang, Ni .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2009, 108 (01) :295-303

[5] "Mesenchymal" Stem Cells [J].

Bianco, Paolo .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :677-704

[6] The Therapeutic Potential, Challenges and Future Clinical Directions of Stem Cells from the Wharton's Jelly of the Human Umbilical Cord [J].

Bongso, Ariff ;

Fong, Chui-Yee .

STEM CELL REVIEWS AND REPORTS, 2013, 9 (02) :226-240

[7] Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system [J].

Chen, Xiang ;

Cui, Jing ;

Yan, Zhengjian ;

Zhang, Hongmei ;

Chen, Xian ;

Wang, Ning ;

Shah, Palak ;

Deng, Fang ;

Zhao, Chen ;

Geng, Nisha ;

Li, Melissa ;

Denduluri, Sahitya K. ;

Haydon, Rex C. ;

Luu, Hue H. ;

Reid, Russell R. ;

He, Tong-Chuan .

GENES & DISEASES, 2015, 2 (01) :96-105

[8] Immortalized Mouse Achilles Tenocytes Demonstrate Long-Term Proliferative Capacity While Retaining Tenogenic Properties [J].

Denduluri, Sahitya K. ;

Scott, Bryan ;

Lamplot, Joseph D. ;

Yin, Liangjun ;

Yan, Zhengjian ;

Wang, Zhongliang ;

Ye, Jixing ;

Wang, Jing ;

Wei, Qiang ;

Mohammed, Maryam K. ;

Haydon, Rex C. ;

Kang, Richard W. ;

He, Tong-Chuan ;

Athiviraham, Aravind ;

Ho, Sherwin H. ;

Shi, Lewis L. .

TISSUE ENGINEERING PART C-METHODS, 2016, 22 (03) :280-289

[9] A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities [J].

Deng, Youlin ;

Wang, Zhongliang ;

Zhang, Fugui ;

Qiao, Min ;

Yan, Zhengjian ;

Wei, Qiang ;

Wang, Jing ;

Liu, Hao ;

Fan, Jiaming ;

Zou, Yulong ;

Liao, Junyi ;

Hu, Xue ;

Chen, Liqun ;

Yu, Xinyi ;

Haydon, Rex C. ;

Luu, Hue H. ;

Qi, Hongbo ;

He, Tong-Chuan ;

Zhang, Junhui .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2016, 39 (03) :871-888

[10] Therapeutic Potentials of Mesenchymal Stem Cells Derived from Human Umbilical Cord [J].

Fan, Cun-Gang ;

Zhang, Qing-jun ;

Zhou, Jing-ru .

STEM CELL REVIEWS AND REPORTS, 2011, 7 (01) :195-207

← 1 2 3 4 5 →