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Co-culture with TM4 cells enhances the proliferation and migration of rat adipose-derived mesenchymal stem cells with high stemness

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Abstract

The proliferation and migration of mesenchymal stem cells (MSCs) are the efficiency determinants in MSCs transplant therapy. Sertoli cells considered as “nurse cell” possesses the ability to enhance the proliferation and migration of umbilical cord mesenchymal stem cells (UCMSCs). However, no reports about TM4 cells' effect on the proliferation and migration of adipose tissue-derived mesenchymal stem cells (ADSCs) have been found until at present research work. Therefore, this study investigates the effect of TM4 cells on the proliferation and migration of ADSCs. We found that the performance of proliferation and migration of ADSCs were improved significantly while maintaining their stemness and reducing their apoptosis rate. After co-culturing with TM4 cells, the co-cultured ADSCs demonstrated higher proportion of synthetic phase (S) cells and colony-forming units-fibroblastic (CFU-F) number, lower proportion of sub-G1 phase cells and enhanced osteogenic and adipogenic differentiation ability. Moreover, results confirmed the higher multiple proteins involved in cell proliferation and migration including expression of the phospho-Akt, mdm2, pho-CDC2, cyclin D1 CXCR4, MMP-2, as well as phospho-p44 MAPK and phospho-p38 MAPK in co-cultured ADSCs. Furthermore, the process of TM4 cells promoting the proliferation of ADSCs was significantly inhibited by the administration of the PI3K/AKT inhibitor LY294002. Obtained results indicated that TM4 cells through MAPK/ERK1/2, MAPK/p-38 and PI3K/Akt pathways influence the proliferation and migration of ADSCs. These findings indicated that TM4 cells were found effective in promoting stemness and migration of ADSCs, that proves adopted co-culturing technique as an efficient approach to obtain ADSCs in transplantation therapy.

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Funding

This research was supported by grants from the National Natural Science Foundation of China (81373286), National Basic Research Program of China (2011CBA00800), and the Fundamental Research Funds for the China Central Universities (Nos. 22221818014 and 22221817014).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai, 200237, China

    Yanxia Luo, Ali Mohsin, Chenze Xu, Qizheng Wang, Haifeng Hang, Yingping Zhuang, Ju Chu & Meijin Guo

  2. Engineering Research Centre of Processes System, Ministry of Education, East China University of Science and Technology, 130 Meilong Rd., Shanghai, 200237, China

    Haifeng Hang, Yingping Zhuang & Meijin Guo

Authors
  1. Yanxia Luo
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  2. Ali Mohsin
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  3. Chenze Xu
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  4. Qizheng Wang
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  5. Haifeng Hang
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  6. Yingping Zhuang
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  7. Ju Chu
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  8. Meijin Guo
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Contributions

This study was designed by MG and HH and experiments were performed by YL, XC and QW. The experimental data was also analyzed by YL. The paper was written by AM, YL and MG. JC and YZ participated in the data discussion. All authors read and approved the final manuscript.

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Correspondence to Haifeng Hang or Meijin Guo.

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Luo, Y., Mohsin, A., Xu, C. et al. Co-culture with TM4 cells enhances the proliferation and migration of rat adipose-derived mesenchymal stem cells with high stemness. Cytotechnology 70, 1409–1422 (2018). https://doi.org/10.1007/s10616-018-0235-3

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