Science China Materials

, Volume 60, Issue 9, pp 892–902 | Cite as

Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers

  • Yan Yang (杨燕)
  • Qiwei Wang (王琪炜)
  • Lina Song (宋丽娜)
  • Xuan Liu (刘璇)
  • Peng Zhao (赵鹏)
  • Feimin Zhang (章非敏)
  • Ning Gu (顾宁)Email author
  • Jianfei Sun (孙剑飞)Email author


With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into cells has become a primary issue for effectively regulating the subsequent safety and performance of nanomaterials in vivo. Although the influence of nanomaterials on endocytosis has been extensively studied, reports on the influence of stem cells are rare. Moreover, the effect of nanomaterials on stem cells is also dependent upon the action mode. Unfortunately, the interaction between stem cells and assembled nanoparticles is often neglected. In this paper, we explore for the first time the uptake of γ-Fe2O3 nanoparticles by adipose-derived stem cells with different passage numbers. The results demonstrate that cellular viability decreases and cell senescence level increases with the extension of the passage number. We found the surface appearance of cellular membranes to become increasingly rough and uneven with increasing passage numbers. The iron content in the dissociative nanoparticles was also significantly reduced with increases in the passage number. However, we observed multiple-passaged stem cells cultured on assembled nanoparticles to have similarly low iron content levels. The mechanism may lie in the magnetic effect of γ-Fe2O3 nanoparticles resulting from the field-directed assembly. The results of this work will facilitate the understanding and translation of nanomaterials in the clinical application of stem cells.


nanoparticles assembly cellular response cell passage uptake 



随着纳米材料在组织工程和再生医学中越来越多的应用, 干细胞和纳米材料之间的相互作用成为关键环节, 而纳米颗粒进入细胞是关系到纳米材料安全性和干细胞命运调控的首要问题. 干细胞传代是其应用中必不可少的过程, 但关于传代代数对干细胞摄取纳米颗粒的影响的研究还较少. 此外, 干细胞和纳米材料的相互作用还与纳米颗粒的存在方式有关. 本文在玻璃片上组装了条带状的γ-Fe2O3纳米颗粒组装结构, 并在该表面上培养SD大鼠脂肪间充质干细胞, 然后研究了不同代数的干细胞对组装和游离的纳米颗粒的吞噬情况. 结果发现, 随着细胞代数增加,细胞活力降低, 细胞衰老水平增加, 并且细胞膜的表面呈现出粗糙和不均匀的形貌. 当与游离的γ-Fe2O3纳米颗粒共培养时, 细胞内铁含量随着代数的增加而减少, 但在组装体上培养的不同代数的细胞具有相似的铁含量, 并且胞内铁含量极少. 另外, 磁感应蛋白的表达表明磁性纳米颗粒的组装体对细胞有磁效应. 该研究表明, 细胞代数的选择对研究颗粒内化实验是至关重要的, 细胞代数应该作为细胞摄取实验的一个重要考虑因素.



This work was supported by the National Basic Research Program of China (2013CB733801) and the National Key Research and Development Program of China (2017YFA0104301). Sun J is thankful to the supports from the Fundamental Research Funds for the Central Universities. All authors are thankful to the supports from Collaborative Innovation Center of Suzhou Nano Science and Technology.

Supplementary material

40843_2017_9088_MOESM1_ESM.pdf (916 kb)
Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers


  1. 1.
    Patel S, Lee KB. Probing stem cell behavior using nanoparticlebased approaches. WIREs Nanomed Nanobiotechnol, 2015, 7: 759–778CrossRefGoogle Scholar
  2. 2.
    Lee IH, Huang SS, Chuang CY, et al. Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke. Sci Rep, 2017, 7: 1943–1955CrossRefGoogle Scholar
  3. 3.
    Laar JMV. Immune ablation and stem-cell therapy in autoimmune disease: immunological reconstitution after high-dose immunosuppression and haematopoietic stem-cell transplantation. Arthritis Res, 2000, 2: 270–275CrossRefGoogle Scholar
  4. 4.
    Wang X, Li G, Guo J, et al. Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model. Exp Ther Med, 2017, 13: 1891–1899CrossRefGoogle Scholar
  5. 5.
    Tancharoen W, Aungsuchawan S, Pothacharoen P, et al. Differentiation of mesenchymal stem cells from human amniotic fluid to vascular endothelial cells. Acta Histochemica, 2017, 119: 113–121CrossRefGoogle Scholar
  6. 6.
    Tong Y, Niu M, Du Y, et al. Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin. Exp Cell Res, 2017, 350: 349–357CrossRefGoogle Scholar
  7. 7.
    Tanthaisong P, Imsoonthornruksa S, Ngernsoungnern A, et al. Enhanced chondrogenic differentiation of human umbilical cord Wharton’s jelly derived mesenchymal stem cells by GSK-3 inhibitors. PLoS ONE, 2017, 12: e0168059CrossRefGoogle Scholar
  8. 8.
    Suzuki A, Saeki T, Ikuji H, et al. Brown algae polyphenol, a prolyl isomerase pin1 inhibitor, prevents obesity by inhibiting the differentiation of stem cells into adipocytes. PLoS ONE, 2016, 11: e0168830CrossRefGoogle Scholar
  9. 9.
    Boquest AC, Shahdadfar A, Brinchmann JE. Isolation of stromal stem cells from human adipose tissue. Methods Mol Biol, 2006, 325: 35–46Google Scholar
  10. 10.
    Lindroos B, Suuronen R, Miettinen S. The potential of adipose stem cells in regenerative medicine. Stem Cell Rev Rep, 2011, 7: 269–291CrossRefGoogle Scholar
  11. 11.
    Geburek F, Roggel F, van Schie HTM, et al. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial. Stem Cell Res Ther, 2017, 8: 129CrossRefGoogle Scholar
  12. 12.
    Hadavi M, Hasannia S, Faghihi S, et al. Novel calcified gum Arabic porous nano-composite scaffold for bone tissue regeneration. Biochem Biophys Res Commun, 2017, 488: 671–678CrossRefGoogle Scholar
  13. 13.
    Liu X, Zhang J, Tang S, et al. Growth enhancing effect of LBLassembled magnetic nanoparticles on primary bone marrow cells. Sci China Mater, 2016, 59: 901–910CrossRefGoogle Scholar
  14. 14.
    Ngadiman NHA, Idris A, Irfan M, et al. γ-Fe2O3 nanoparticles filled polyvinyl alcohol as potential biomaterial for tissue engineering scaffold. J Mech Behav Biomed Mater, 2015, 49: 90–104CrossRefGoogle Scholar
  15. 15.
    Lu L, Unsworth LD. pH-Triggered release of hydrophobic molecules from self-assembling hybrid nanoscaffolds. Biomacromolecules, 2016, 17: 1425–1436CrossRefGoogle Scholar
  16. 16.
    Verma A, Uzun O, Hu Y, et al. Surface-structure-regulated cellmembrane penetration by monolayer-protected nanoparticles. Nat Mater, 2008, 7: 588–595CrossRefGoogle Scholar
  17. 17.
    Gu JL, Xu HF, Han YH, et al. The internalization pathway, metabolic fate and biological effect of superparamagnetic iron oxide nanoparticles in the macrophage-like RAW264.7 cell. Sci China Life Sci, 2011, 54: 793–805CrossRefGoogle Scholar
  18. 18.
    Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release, 2010, 145: 182–195CrossRefGoogle Scholar
  19. 19.
    Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature, 2003, 422: 37–44CrossRefGoogle Scholar
  20. 20.
    Zhao P, Cao M, Song L, et al. Downregulation of MIM protein inhibits the cellular endocytosis process of magnetic nanoparticles in macrophages. RSC Adv, 2016, 6: 96635–96643CrossRefGoogle Scholar
  21. 21.
    da Luz CM, Boyles MSP, Falagan-Lotsch P, et al. Poly-lactic acid nanoparticles (PLA-NP) promote physiological modifications in lung epithelial cells and are internalized by clathrin-coated pits and lipid rafts. J Nanobiotechnol, 2017, 15: 11–29CrossRefGoogle Scholar
  22. 22.
    Banerjee A, Berezhkovskii A, Nossal R. Kinetics of cellular uptake of viruses and nanoparticles via clathrin-mediated endocytosis. Phys Biol, 2016, 13: 016005CrossRefGoogle Scholar
  23. 23.
    Scheinpflug DK. Measurement of cell membrane fluidity by laurdan GP: fluorescence spectroscopy and microscopy. Methods Mol Biol, 2017, 1520: 159–174CrossRefGoogle Scholar
  24. 24.
    Wang Q, Chen B, Cao M, et al. Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials, 2016, 86: 11–20CrossRefGoogle Scholar
  25. 25.
    Sun J, Liu X, Huang J, et al. Magnetic assembly-mediated enhancement of differentiation of mouse bone marrow cells cultured on magnetic colloidal assemblies. Sci Rep, 2015, 4: 5125CrossRefGoogle Scholar
  26. 26.
    Chamberlain G, Fox J, Ashton B, et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 2007, 25: 2739–2749CrossRefGoogle Scholar
  27. 27.
    Sufian MM, Khattak JZK, Yousaf S, et al. Safety issues associated with the use of nanoparticles in human body. Photodiagnosis Photodynamic Ther, 2017, 19: 67–72CrossRefGoogle Scholar
  28. 28.
    Decuzzi P, Ferrari M. The receptor-mediated endocytosis of nonspherical particles. BioPhys J, 2008, 94: 3790–3797CrossRefGoogle Scholar
  29. 29.
    Qin S, Yin H, Yang C, et al. A magnetic protein biocompass. Nat Mater, 2015, 15: 217–226CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Yan Yang (杨燕)
    • 1
  • Qiwei Wang (王琪炜)
    • 1
  • Lina Song (宋丽娜)
    • 1
  • Xuan Liu (刘璇)
    • 2
  • Peng Zhao (赵鹏)
    • 1
  • Feimin Zhang (章非敏)
    • 3
  • Ning Gu (顾宁)
    • 1
    Email author
  • Jianfei Sun (孙剑飞)
    • 1
    Email author
  1. 1.State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical EngineeringSoutheast UniversityNanjingChina
  2. 2.School of MedicineSoutheast UniversityNanjingChina
  3. 3.Stomatological Hospital of Jiangsu ProvinceNanjingChina

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