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Effects of labeling human mesenchymal stem cells with superparamagnetic zinc–nickel ferrite nanoparticles on cellular characteristics and adipogenesis/osteogenesis differentiation

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Abstract

Objective

An attractive cell source for stem cell-based therapy are WJ-MSCs. Hence, tracking WJ-MSCs using non-invasive imaging procedures (such as MRI) and contrast agents (Zn0.5Ni0.5Fe2O4, NFNPs) are required to evaluate cell distribution, migration, and differentiation.

Results

Results showed that the bare and dextrin-coated NFNPs were internalized inside the WJ-MSCs and had no effect on the cell viability, proliferation, apoptosis, karyotyping, and morphology of WJ-MSCs up to 125 µg/mL. Besides, treated WJ-MSCs were differentiated into osteo/adipocyte-like cells. The expression of RUNX 2, SPP 1 (P < 0.05), and OCN (P > 0.05) genes in the WJ-MSCs treated with dextrin-coated NFNPs was higher than the untreated WJ-MSCs; and the expression of CFD, LPL, and PPAR-γ genes was reduced in WJ-MSCs treated with both NFNPs in comparison with the untreated WJ-MSCs (P > 0.05).

Conclusion

Overall, results showed that dextrin-coated NFNPs had no adverse effect on the cellular characteristics, proliferation, and differentiation of WJ-MSCs, and suggesting their potential clinical efficacy.

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Data availability

All data is made available and presented in the manuscript.

Abbreviations

WJ-MSCs:

Wharton’s jelly mesenchymal stem cells

LPL:

Lipoprotein lipase

CFD:

Complement factor D,

PPARγ:

Peroxisome proliferator-activated receptor-gamma,

OCN:

Bone gamma-carboxyglutamate protein,

SPP:

Secreted phosphoprotein 1

RUNX 2:

Runt related transcription factor 2, and

NFNPs:

Zn0.5Ni0.5Fe2O4 nanoparticles

References

  • Addicott B, Willman M, Rodriguez J, Padgett K, Han D, Berman D, Hare JM, Kenyon NS (2011) Mesenchymal stem cell labeling and in vitro MR characterization at 1.5 T of new SPIO contrast agent: Molday ION Rhodamine-B™. Contrast Media Mol Imaging 6(1):7–18

    CAS  PubMed  Google Scholar 

  • Ahn YJ, Kong TH, Choi JS, Yun WS, Key J, Seo YJ (2019) Strategies to enhance efficacy of SPION-labeled stem cell homing by magnetic attraction: a systemic review with meta-analysis. Int J Nanomed 14:4849

    CAS  Google Scholar 

  • Anderson SA, Glod J, Arbab AS, Noel M, Ashari P, Fine HA, Frank JA (2005) Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood 105(1):420–425

    CAS  PubMed  Google Scholar 

  • Astolfo A, Schültke E, Menk RH, Kirch RD, Juurlink BH, Hall C, Harsan L-A, Stebel M, Barbetta D, Tromba G (2013) In vivo visualization of gold-loaded cells in mice using x-ray computed tomography. Nanomed Nanotechnol Biol Med 9(2):284–292

    CAS  Google Scholar 

  • Bao C, Conde J, Polo E, Del Pino P, Moros M, Baptista PV, Grazu V, Cui D, De La Fuente JM (2014) A promising road with challenges: where are gold nanoparticles in translational research? Nanomedicine 9(15):2353–2370

    CAS  PubMed  Google Scholar 

  • Bulte JW (2005) Magnetic nanoparticles as markers for cellular MR imaging. J Magn Magn Mater 289:423–427

    CAS  Google Scholar 

  • Bulte JW, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17(7):484–499

    CAS  PubMed  Google Scholar 

  • Bulte JW, Douglas T, Witwer B, Zhang S-C, Strable E, Lewis BK, Zywicke H, Miller B, Van Gelderen P, Moskowitz BM (2001) Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol 19(12):1141–1147

    CAS  PubMed  Google Scholar 

  • Chen Y-C, Hsiao J-K, Liu H-M, Lai I-Y, Yao M, Hsu S-C, Ko B-S, Chen Y-C, Yang C-S, Huang D-M (2010) The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Toxicol Appl Pharmacol 245(2):272–279

    CAS  PubMed  Google Scholar 

  • Cromer Berman SM, Walczak P, Bulte JW (2011) Tracking stem cells using magnetic nanoparticles. Wiley Interdiscip Rev 3(4):343–355

    Google Scholar 

  • Decuzzi P, Ferrari M (2007) The role of specific and non-specific interactions in receptor-mediated endocytosis of nanoparticles. Biomaterials 28(18):2915–2922

    CAS  PubMed  Google Scholar 

  • Deddens LH, Van Tilborg GA, Mulder WJ, De Vries HE, Dijkhuizen RM (2012) Imaging neuroinflammation after stroke: current status of cellular and molecular MRI strategies. Cerebrovasc Dis 33(4):392–402

    CAS  PubMed  Google Scholar 

  • Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    CAS  PubMed  Google Scholar 

  • Elsherbini AA, Saber M, Aggag M, El-Shahawy A, Shokier HA (2011) Magnetic nanoparticle-induced hyperthermia treatment under magnetic resonance imaging. Magn Reson Imaging 29(2):272–280

    PubMed  Google Scholar 

  • Fan C-G, Zhang Q-J, Zhou J-R (2011) Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev Rep 7(1):195–207

    PubMed  Google Scholar 

  • Ferreira L, Karp JM, Nobre L, Langer R (2008) New opportunities: the use of nanotechnologies to manipulate and track stem cells. Cell Stem Cell 3(2):136–146

    CAS  PubMed  Google Scholar 

  • Forte E, Fiorenza D, Torino E, Costagliola di Polidoro A, Cavaliere C, Netti PA, Salvatore M, Aiello M (2020) Radiolabeled PET/MRI Nanoparticles for Tumor Imaging. J Clin Med 9(1):89

    CAS  Google Scholar 

  • Gillingham AK, Munro S (2007) The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol 23:579–611

    CAS  PubMed  Google Scholar 

  • Girao H, Geli M-I, Idrissi F-Z (2008) Actin in the endocytic pathway: from yeast to mammals. FEBS Lett 582(14):2112–2119

    CAS  PubMed  Google Scholar 

  • Guenoun J, Koning GA, Doeswijk G, Bosman L, Wielopolski PA, Krestin GP, Bernsen MR (2012) Cationic Gd-DTPA liposomes for highly efficient labeling of mesenchymal stem cells and cell tracking with MRI. Cell Transplant 21(1):191–205

    PubMed  Google Scholar 

  • Guzman R, Bliss T, De Los Angeles A, Moseley M, Palmer T, Steinberg G (2008) Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset. J Neurosci Res 86(4):873–882

    CAS  PubMed  Google Scholar 

  • Hai TH, Phuc LH, Long BD, Vinh LK, Abe M (2008) Contrast agents for magnetic resonance imaging based on ferrite nanoparticles synthesized by using a wet-chemical method. J Korean Phys Soc 53:772

    CAS  Google Scholar 

  • Heli H, Sattarahmady N, Hatam G, Reisi F, Vais RD (2016) An electrochemical genosensor for Leishmania major detection based on dual effect of immobilization and electrocatalysis of cobalt-zinc ferrite quantum dots. Talanta 156:172–179

    PubMed  Google Scholar 

  • Hong H, Yang Y, Zhang Y, Cai W (2010) Non-invasive cell tracking in cancer and cancer therapy. Curr Top Med Chem 10(12):1237–1248

    CAS  PubMed  PubMed Central  Google Scholar 

  • Howes MT, Kirkham M, Riches J, Cortese K, Walser PJ, Simpson F, Hill MM, Jones A, Lundmark R, Lindsay MR (2010) Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. J Cell Biol 190(4):675–691

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsiao JK, Tai MF, Chu HH, Chen ST, Li H, Lai DM, Hsieh ST, Wang JL, Liu HM (2007) Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: cellular behavior and capability of detection with clinical 15 T magnetic resonance at the single cell level. Magn Reson Med 58(4):717–724

    CAS  PubMed  Google Scholar 

  • Ito A, Shinkai M, Honda H, Kobayashi T (2005) Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 100(1):1–11

    CAS  PubMed  Google Scholar 

  • Iwanami A, Kaneko S, Nakamura M, Kanemura Y, Mori H, Kobayashi S, Yamasaki M, Momoshima S, Ishii H, Ando K (2005) Transplantation of human neural stem cells for spinal cord injury in primates. J Neurosci Res 80(2):182–190

    CAS  PubMed  Google Scholar 

  • Jasmin GTDS, Louzada RA, Rosado-de-Castro PH, Mendez-Otero R, de Carvalho ACC (2017) Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations. Int J Nanomed 12:779

    CAS  Google Scholar 

  • Jomura S, Uy M, Mitchell K, Dallasen R, Bode CJ, Xu Y (2007) Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix cells. Stem Cells 25(1):98–106

    CAS  PubMed  Google Scholar 

  • Kabat M, Bobkov I, Kumar S, Grumet M (2020) Trends in mesenchymal stem cell clinical trials 2004–2018: is efficacy optimal in a narrow dose range? Stem Cells Transl Med 9(1):17–27

    CAS  PubMed  Google Scholar 

  • Kim D, Zhang Y, Kehr J, Klason T, Bjelke B, Muhammed M (2001) Characterization and MRI study of surfactant-coated superparamagnetic nanoparticles administered into the rat brain. J Magn Magn Mater 225(1–2):256–261

    CAS  Google Scholar 

  • Lee ES, Shuter B, Chan J, Chong MS, Ding J, Teoh S-H, Beuf O, Briguet A, Tam KC, Choolani M (2010) The use of microgel iron oxide nanoparticles in studies of magnetic resonance relaxation and endothelial progenitor cell labelling. Biomaterials 31(12):3296–3306

    CAS  PubMed  Google Scholar 

  • Li X-X, Li K-A, Qin J-B, Ye K-C, Yang X-R, Li W-M, Xie Q-S, Jiang M-E, Zhang G-X, Lu X-W (2013) In vivo MRI tracking of iron oxide nanoparticle-labeled human mesenchymal stem cells in limb ischemia. Int J Nanomed 8:1063

    Google Scholar 

  • Liao N, Wu M, Pan F, Lin J, Li Z, Zhang D, Wang Y, Zheng Y, Peng J, Liu X (2016) Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells. Sci Rep 6:18746

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F, Gätjens J (2011) Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging. Biomaterials 32(26):6155–6163

    CAS  PubMed  Google Scholar 

  • Luo C, Li Y, Yang L, Wang X, Long J, Liu J (2015) Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses. Arch Toxicol 89(3):357–369

    CAS  PubMed  Google Scholar 

  • Ma HL, Xu YF, Qi XR, Maitani Y, Nagai T (2008) Superparamagnetic iron oxide nanoparticles stabilized by alginate: pharmacokinetics, tissue distribution, and applications in detecting liver cancers. Int J Pharm 354(1–2):217–226

    CAS  PubMed  Google Scholar 

  • Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, Häfeli UO, Stroeve P (2010) A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. Colloids Surf, B 75(1):300–309

    CAS  Google Scholar 

  • Mailänder V, Lorenz MR, Holzapfel V, Musyanovych A, Fuchs K, Wiesneth M, Walther P, Landfester K, Schrezenmeier H (2008) Carboxylated superparamagnetic iron oxide particles label cells intracellularly without transfection agents. Mol Imag Biol 10(3):138–146

    Google Scholar 

  • Malgieri A, Kantzari E, Patrizi MP, Gambardella S (2010) Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med 3(4):248

    PubMed  PubMed Central  Google Scholar 

  • Marques A, Reis R, Hunt J (2002) The biocompatibility of novel starch-based polymers and composites: in vitro studies. Biomaterials 23(6):1471–1478

    CAS  PubMed  Google Scholar 

  • Niemirowicz K, Markiewicz K, Wilczewska A, Car H (2012) Magnetic nanoparticles as new diagnostic tools in medicine. Adv Med Sci 57(2):196–207

    CAS  PubMed  Google Scholar 

  • Patil RM, Thorat ND, Shete PB, Bedge PA, Gavde S, Joshi MG, Tofail SA, Bohara RA (2018) Comprehensive cytotoxicity studies of superparamagnetic iron oxide nanoparticles. Biochemistry and biophysics reports 13:63–72

    PubMed  PubMed Central  Google Scholar 

  • Portet D, Denizot B, Rump E, Lejeune J-J, Jallet P (2001) Nonpolymeric coatings of iron oxide colloids for biological use as magnetic resonance imaging contrast agents. J Colloid Interface Sci 238(1):37–42

    CAS  PubMed  Google Scholar 

  • Raynal I, Prigent P, Peyramaure S, Najid A, Rebuzzi C, Corot C (2004) Macrophage endocytosis of superparamagnetic iron oxide nanoparticles: mechanisms and comparison of ferumoxides and ferumoxtran-10. Invest Radiol 39(1):56–63

    CAS  PubMed  Google Scholar 

  • Ren Z, Wang J, Zou C, Guan Y, Zhang YA (2011) Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging. Sci China Life Sci 54(11):981–987

    PubMed  Google Scholar 

  • Riegler J, Liew A, Hynes SO, Ortega D, O’Brien T, Day RM, Richards T, Sharif F, Pankhurst QA, Lythgoe MF (2013) Superparamagnetic iron oxide nanoparticle targeting of MSCs in vascular injury. Biomaterials 34(8):1987–1994

    CAS  PubMed  Google Scholar 

  • Rosenberg JT, Yuan X, Helsper SN, Bagdasarian FA, Ma T, Grant SC (2018) Effects of labeling human mesenchymal stem cells with superparamagnetic iron oxides on cellular functions and magnetic resonance contrast in hypoxic environments and long-term monitoring. Brain Circ 4(3):133

    PubMed  PubMed Central  Google Scholar 

  • Sattarahmady N, Heidari M, Zare T, Lotfi M, Heli H (2016) Zinc–nickel ferrite nanoparticles as a contrast agent in magnetic resonance imaging. Appl Magn Reson 47(8):925–935

    CAS  Google Scholar 

  • Shapiro EM, Skrtic S, Sharer K, Hill JM, Dunbar CE, Koretsky AP (2004) MRI detection of single particles for cellular imaging. Proc Natl Acad Sci 101(30):10901–10906

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shapiro EM, Sharer K, Skrtic S, Koretsky AP (2006) In vivo detection of single cells by MRI. Magn Reson Med 55(2):242–249

    PubMed  Google Scholar 

  • Sharifi S, Daghighi S, Motazacker M, Badlou B, Sanjabi B, Akbarkhanzadeh A, Rowshani A, Laurent S, Peppelenbosch M, Rezaee F (2013) Superparamagnetic iron oxide nanoparticles alter expression of obesity and T2D-associated risk genes in human adipocytes. Sci Rep 3(1):1–12

    Google Scholar 

  • Silva LH, Silva JR, Ferreira GA, Silva RC, Lima EC, Azevedo RB, Oliveira DM (2016) Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: assessment of biocompatibility and potential applications. Journal Nanobiotechnol 14(1):59

    Google Scholar 

  • Stroh A, Kressel J, Coras R, Dreyer AY, Fröhlich W, Förschler A, Lobsien D, Blümcke I, Zoubaa S, Schlegel J (2019) A safe and effective magnetic labeling protocol for MRI-based tracking of human adult neural stem cells. Front Neurosci. https://doi.org/10.3389/fnins.2019.01092

    Article  PubMed  PubMed Central  Google Scholar 

  • Taboada E, Rodríguez E, Roig A, Oró J, Roch A, Muller RN (2007) Relaxometric and magnetic characterization of ultrasmall iron oxide nanoparticles with high magnetization. Evaluation as potential T1 magnetic resonance imaging contrast agents for molecular imaging. Langmuir 23(8):4583–4588

    CAS  PubMed  Google Scholar 

  • Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, Armstrong L, Djonov V, Lako M, Stojkovic M (2018) Ethical and safety issues of stem cell-based therapy. Int J Med Sci 15(1):36

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Xu F, Zhang C, Lei D, Tang Y, Xu H, Zhang Z, Lu H, Du X, Yang G-Y (2011) High MR sensitive fluorescent magnetite nanocluster for stem cell tracking in ischemic mouse brain. Nanomedicine 7(6):1009–1019

    CAS  PubMed  Google Scholar 

  • Wang N, Zhao JY, Guan X, Dong Y, Liu Y, Zhou X, R. a. Wu, Y. Du, L. Zhao and W. Zou, (2015) Biological characteristics of adipose tissue-derived stem cells labeled with amine-surface-modified superparamagnetic iron oxide nanoparticles. Cell Biol Int 39(8):899–909

    CAS  PubMed  Google Scholar 

  • Wei L, Li S, Yang J, Ye Y, Zou J, Wang L, Long R, Zurkiya O, Zhao T, Johnson J (2011) Protein-based MRI contrast agents for molecular imaging of prostate cancer. Mol Imag Biol 13(3):416–423

    Google Scholar 

  • Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D (2006) Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem cells 24(3):781–792

    CAS  PubMed  Google Scholar 

  • Weissleder R, Elizondo G, Wittenberg J, Lee A, Josephson L, Brady T (1990) Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 175(2):494–498

    CAS  PubMed  Google Scholar 

  • Wong WH, Mooney DJ (1997) Synthesis and properties of biodegradable polymers used as synthetic matrices for tissue engineering. Synthetic biodegradable polymer scaffolds. Springer, Birkhäuser Boston, pp 51–82

    Google Scholar 

  • Yahyapour R, Farhood B, Graily G, Rezaeyan A, Rezapoor S, Abdollahi H, Cheki M, Amini P, Fallah H, Najafi M (2018) Stem cell tracing through MR molecular imaging. Tissue Eng Regen Med 15(3):249–261

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang P, He X, Li H, Lan B, Wang D, Wang G, Xu S, Liu Y (2008) Reactive astrocytes and nestin expression in adult rats following spinal cord compression injury. J South Med Univ 28(10):1752–1755

    CAS  Google Scholar 

  • Youn H, Hong K-J (2012) In vivo non invasive molecular imaging for immune cell tracking in small animals. Immune Netw 12(6):223–229

    PubMed  PubMed Central  Google Scholar 

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Acknowledgement

The present article was supported by the Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran and Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Nanomedicine and Nanobiology Research Center, Shiraz University of Medical. The study team would like to gratefully acknowledge to staff of this center for their sincere cooperation.

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Correspondence to Farzaneh Zarghampoor or Negar Azarpira.

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This research was approved by the council and ethics committee of Shiraz University of medical Sciences-Iran with the ethical gridlines of the Helsinki Declaration of 1975 (the ethics code IR.SUMS.REC. 1397.752).

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Ghanbarei, S., Sattarahmady, N., Zarghampoor, F. et al. Effects of labeling human mesenchymal stem cells with superparamagnetic zinc–nickel ferrite nanoparticles on cellular characteristics and adipogenesis/osteogenesis differentiation. Biotechnol Lett 43, 1659–1673 (2021). https://doi.org/10.1007/s10529-021-03134-w

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