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Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents

Cytotechnology volume 63, Article number: 523 (2011) Cite this article

Abstract

Human adipose derived mesenchymal stem cells (ADMSCs) are multipotential stem cells, originated from the vascular stromal compartment of fat tissues which can be used as an alternative cell source for many different cell therapies. However, their response to chemotherapeutic agants remains unknown. Here we assessed the acute direct effects of individual chemotherapeutic drug on ADMSCs. Using an in vitro culture system, the response of ADMSCs to the three chemotherapeutic agents cisplatin, comptothecin and vincristine was determined in comparison with that of testicular germ cell tumour (TGCT) cell line. The recovery of cell numbers following exposure to chemotherapeutic agents were also evaluated. Our results showed that human ADMSCs were resistant to chemo-therapeutic agents which are commonly used in clinic, the full recovery was seen respectively in ADMSCs after the drug treatment. Moreover, ADMSCs maintained their stem cell characteristics in vitro after the exposure to all chemotherapeutic agents.

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Abbreviations

ADMSC:

Adipose derived mesenchymal stem cell

MSCs:

Mesenchymal stem cells

XTT:

2,3-Bis(2-methoxy-4-nitro-5-sulphophenyl)-5-((phenylamino)carbonyl)2H-tetrazolium hydroxide

FITC:

Fluoresein-5-isothiocyanate

FACS:

Fluorescence-activated cell sorting

References

  • Almohamad K, Thiry A, Hubin F, Belaid Z, Humblet C, Boniver J, Defresne MP (2003) Marrow stromal cell recovery after radiation-induced aplasia in mice. Int J Rad Biol 79:259–267

    Article  CAS  Google Scholar 

  • Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC (2005) Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 332:370–379

    Article  CAS  Google Scholar 

  • Chen MF, Lin CT, Chen WC, Yang CT, Chen CC, Liao SK, Liu JM, Lu CH, Lee KD (2006) The sensitivity of human mesenchymal stem cells to ionizing radiation. Int J Rad Oncol Biol Phys 66:244–253

    Article  CAS  Google Scholar 

  • Devine SM, Hoffman R (2000) Role of mesenchymal stem cells in hematopoietic stem cell transplantation. Curr Opin Hematol 7:358–363

    Article  CAS  Google Scholar 

  • Garcia-Gomez I, Elvira G, Zapata AG, Lamana ML, Ramirez M, Castro JG, Arranz MG, Vicente A, Bueren J, Garcia-Olmo D (2004) Mesenchymal stem cells: biological properties and clinical applications. Expert Opin Biol Ther 10:1453–1468

    Article  Google Scholar 

  • Gimble JM, Robinson CE, Wu X, Kelly KA, Rodriguez BR, Kliewer SA, Lehmann JM, Morris DC (1996) Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol 50:1087–1094

    CAS  Google Scholar 

  • Grisendi G, Bussolari R, Cafarelli L, Petak I, Rasini V, Veronesi E, De Santis G, Spano C, Tagliazzucchi M, Barti-Juhasz H, Scarabelli L, Bambi F, Frassoldati A, Rossi G, Casali C, Morandi U, Horwitz EM, Paolucci P, Conte P, Dominici M (2003) Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res 70:3718–3729

    Article  Google Scholar 

  • Heyer BS, MacAuley A, Behrendtsen O, Werb Z (2000) Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development. Gen Dev 14:2072–2084

    CAS  Google Scholar 

  • Kern S, Eichler H, Stoeve J, Kluter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells (Dayton, Ohio) 24:1294–1301

    Article  CAS  Google Scholar 

  • Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marr Transplant 30:215–222

    Article  CAS  Google Scholar 

  • Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96:10711–10716

    Article  CAS  Google Scholar 

  • Li J, Law HK, Lau YL, Chan GC (2004) Differential damage and recovery of human mesenchymal stem cells after exposure to chemotherapeutic agents. Br J Haematol 127:326–334

    Article  CAS  Google Scholar 

  • Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286

    Article  CAS  Google Scholar 

  • Mueller LP, Luetzkendorf J, Mueller T, Reichelt K, Simon H, Schmoll HJ (2006) Presence of mesenchymal stem cells in human bone marrow after exposure to chemotherapy: evidence of resistance to apoptosis induction. Stem Cells (Dayton, Ohio) 24:2753–2765

    Article  CAS  Google Scholar 

  • Muguruma Y, Reyes M, Nakamura Y, Sato T, Matsuzawa H, Miyatake H, Akatsuka A, Itoh J, Yahata T, Ando K, Kato S, Hotta T (2003) In vivo and in vitro differentiation of myocytes from human bone marrow-derived multipotent progenitor cells. Exp Hematol 31:1323–1330

    Article  CAS  Google Scholar 

  • Muraglia A, Cancedda R, Quarto R (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 113(Pt 7):1161–1166

    CAS  Google Scholar 

  • Pak HN, Qayyum M, Kim DT, Hamabe A, Miyauchi Y, Lill MC, Frantzen M, Takizawa K, Chen LS, Fishbein MC, Sharifi BG, Chen PS, Makkar R (2003) Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a Swine model of myocardial infarction. J Cardiovasc Electrophysiol 14:841–848

    Article  Google Scholar 

  • Parsons CH, Szomju B, Kedes DH (2004) Susceptibility of human fetal mesenchymal stem cells to Kaposi sarcoma-associated herpesvirus. Blood 104:2736–2738

    Article  CAS  Google Scholar 

  • Pereira RF, O’Hara MD, Laptev AV, Halford KW, Pollard MD, Class R, Simon D, Livezey K, Prockop DJ (1998) Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci USA 95:1142–1147

    Article  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  Google Scholar 

  • Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98

    Article  Google Scholar 

  • Wakitani S, Saito T, Caplan AI (1995) Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18:1417–1426

    Article  CAS  Google Scholar 

  • Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370

    Article  CAS  Google Scholar 

  • Zuk PA (2005) The adipose-derived stem cell: looking back and looking ahead. Mol Biol Cell 21:1783–1787

    Article  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the “863 Projects” of Minsitry of Science and Technology of PR China (No 2002 AA 205061); and from Beijing Minsitry of Science and Technology (No. 2002-489).

Conflict of interest

The authors declare no conflict of interest.

Author information

Affiliations

  1. Department of Oncology, Center for Cell Therapy and Tissue Engineering, The First Affiliated Hospital of Anhui Medical University, 218# Jixi Road, Hefei, 230022, Anhui Province, People’s Republic of China

    Wei Liang & Hailong Xia

  2. Institute of Basic Medical Science and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China

    Jing Li & Robert Chunhua Zhao

Authors
  1. Wei Liang
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  2. Hailong Xia
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  3. Jing Li
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  4. Robert Chunhua Zhao
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Correspondence to Wei Liang.

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Liang, W., Xia, H., Li, J. et al. Human adipose tissue derived mesenchymal stem cells are resistant to several chemotherapeutic agents. Cytotechnology 63, 523 (2011). https://doi.org/10.1007/s10616-011-9374-5

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  • DOI: https://doi.org/10.1007/s10616-011-9374-5

Keywords

  • Adipose tissue
  • MSCs
  • Chemoresistance
  • Cisplatin
  • Vincristine
  • Camptothecin