Establishing and characterizing human stem cells from the apical papilla immortalized by hTERT gene transfer

作者全名："Cheng, Qianyu; Liu, Chang; Chen, Qiuman; Luo, Wenping; He, Tong-Chuan; Yang, Deqin"

作者地址："[Cheng, Qianyu; Liu, Chang; Yang, Deqin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Cheng, Qianyu; Liu, Chang; Yang, Deqin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Cheng, Qianyu; Liu, Chang; Yang, Deqin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Cheng, Qianyu; Liu, Chang; Yang, Deqin] Chongqing Med Univ, Dept Endodont, Stomatol Hosp, Chongqing, Peoples R China; [Chen, Qiuman] Hainan Women & Childrens Med Ctr, Dept Stomatol, Haikou, Peoples R China; [Luo, Wenping] Southwest Univ, Lab Anim Ctr, Chongqing, Peoples R China; [He, Tong-Chuan] Univ Chicago, Dept Orthopaed Surg & Rehabil Med, Mol Oncol Lab, Med Ctr, Chicago, IL USA"

通信作者："Yang, DQ (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Yang, DQ (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China.; Yang, DQ (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Yang, DQ (通讯作者)，Chongqing Med Univ, Dept Endodont, Stomatol Hosp, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000999598400001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：stem cells from the apical papilla (SCAP); hTERT; immortalization; BMP9; osteogenic differentiation

摘要："Stem cells from the apical papilla (SCAPs) are promising candidates for regenerative endodontic treatment and tissue regeneration in general. However, harvesting enough cells from the limited apical papilla tissue is difficult, and the cells lose their primary phenotype over many passages. To get over these challenges, we immortalized human SCAPs with lentiviruses overexpressing human telomerase reverse transcriptase (hTERT). Human immortalized SCAPs (hiSCAPs) exhibited long-term proliferative activity without tumorigenic potential. Cells also expressed mesenchymal and progenitor biomarkers and exhibited multiple differentiation potentials. Interestingly, hiSCAPs gained a stronger potential for osteogenic differentiation than the primary cells. To further investigate whether hiSCAPs could become prospective seed cells in bone tissue engineering, in vitro and in vivo studies were performed, and the results indicated that hiSCAPs exhibited strong osteogenic differentiation ability after infection with recombinant adenoviruses expressing BMP9 (AdBMP9). In addition, we revealed that BMP9 could upregulate ALK1 and BMPRII, leading to an increase in phosphorylated Smad1 to induce the osteogenic differentiation of hiSCAPs. These results support the application of hiSCAPs in tissue engineering/regeneration schemes as a stable stem cell source for osteogenic differentiation and biomineralization, which could be further used in stem cell-based clinical therapies."

基金机构："National Natural Science Foundation of China [31970783, 32270888, 32070539]; Program for Top talent Distinguished Professor from Chongqing Medical University [2021215]; Program for Youth Innovation in Future Medicine from Chongqing Medical University [W0060]"

基金资助正文："Funding The reported work was supported in part by research grants from the Project Supported by the National Natural Science Foundation of China (No. 31970783 to DY, No. 32270888 to DY, No. 32070539 to WL), Program for Top talent Distinguished Professor from Chongqing Medical University to DY (No. 2021215), Program for Youth Innovation in Future Medicine from Chongqing Medical University (No. W0060 to DY)."