Vet Comp Orthop Traumatol 2022; 35(06): 362-369
DOI: 10.1055/s-0042-1750432
Original Research

MRI Tracking of Iron Oxide Labelled Canine Mesenchymal Stem Cells in Artificial Stifle Defects

Kerstin von Pueckler
1   Department of Veterinary Clinical Science, Small Animal Clinic, Justus Liebig University, Gießen, Germany
,
Karen John
1   Department of Veterinary Clinical Science, Small Animal Clinic, Justus Liebig University, Gießen, Germany
,
Martin Kramer
1   Department of Veterinary Clinical Science, Small Animal Clinic, Justus Liebig University, Gießen, Germany
,
Jan Bokemeyer
2   Tierklinik Kalbach – Fachklinik für Kleintiere Frankfurt, Frankfurt am Main, Germany
,
Stefan Arnhold
3   Institute of Veterinary Anatomy and Embryology, Justus Liebig University, Gießen, Germany
› Author Affiliations
Funding None.

Abstract

Objectives The aim of this study was to describe ultrasmall superparamagnetic iron oxides labelling of canine adipose-derived mesenchymal stem cells (AdMSCs) and the detection and semiquantitative evaluation of the labelled cells after implantation in artificial canine stifle defects using magnetic resonance imaging.

Methods Magnetic resonance imaging examinations of 10 paired (n = 20) cadaveric stifle joints were evaluated after creation of chondral defects and embedding of ultrasmall superparamagnetic iron oxides labelled canine mesenchymal stem cells. To prove the feasibility of the labelling for in vivo usage, Prussian blue staining, cell vitality tests and intralesional administration of labelled cells were conducted. Magnetic resonance imaging of ex vivo defects filled with different cell concentrations was obtained to depict the cell content semiquantitatively via signal intensity measurements (region of interest).

Results Prussian blue staining showed that the labelling was effective. According to the vitality tests, it had no significant short-term influence on cell viability and proliferation rate. For the evaluation of the defect T2* sequences were feasible and stifle defects were visible allowing measurements of the signal intensity in all cases. Increasing the cell concentration within the chondral defects resulted in an inversely proportional, significant reduction of signal intensity according to the region of interest.

Clinical Significance Ultrasmall superparamagnetic iron oxides labelling was effective. The detection of the AdMSCs in a complex anatomical structure like the surface of the femoral condyle was possible and the T2* signal intensity of the implant region was significantly correlated with the concentration of the AdMSCs.

Authors' Contribution

K.V.P., K.J, and S.A. contributed to the conception of study, study design, acquisition of data, data analysis and interpretation, drafting or revising of manuscript, approval of submitted manuscript and are publicly accountable for relevant content. M.K. and J.B. contributed to the conception of study, study design, data analysis and interpretation, drafting or revising of manuscript, approval of submitted manuscript and are publicly accountable for relevant content.


Supplementary Material



Publication History

Received: 30 June 2021

Accepted: 04 May 2021

Article published online:
05 July 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Meyer-Lindenberg A, Kilchling T. [Use of mesenchymal stemcells in dogs]. Tierarztl Prax Ausg K Klientiere Heimtiere 2018; 46 (06) 416-425
  • 2 Arnhold S, Wenisch S. Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine. Am J Stem Cells 2015; 4 (01) 1-12
  • 3 Liu Y, Chen F, Liu W. et al. Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage. Tissue Eng 2002; 8 (04) 709-721
  • 4 Guo X, Wang C, Zhang Y. et al. Repair of large articular cartilage defects with implants of autologous mesenchymal stem cells seeded into β-tricalcium phosphate in a sheep model. Tissue Eng 2004; 10 (11-12): 1818-1829
  • 5 Kazemi D, Shams Asenjan K, Dehdilani N, Parsa H. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: macroscopic and histological assessments. Bone Joint Res 2017; 6 (02) 98-107
  • 6 Olsson SE. Pathology, morphology, and clinical signs of osteochondrosis in the dog. In: Bojrab MJ, Bloomberg M, Smeak D. . eds. Disease Mechanisms in Small Animal Surgery. Philadelphia: Lippincott Williams & Wilkins; 1993: 777
  • 7 Jackson DW, Scheer MJ, Simon TM. Cartilage substitutes: overview of basic science and treatment options. J Am Acad Orthop Surg 2001; 9 (01) 37-52
  • 8 Thiede RM, Lu Y, Markel MD. A review of the treatment methods for cartilage defects. Vet Comp Orthop Traumatol 2012; 25 (04) 263-272
  • 9 Kim SE, Pozzi A, Yeh JC. et al. Intra-articular umbilical cord derived mesenchymal stem cell therapy for chronic elbow osteoarthritis in dogs: a double-blinded, placebo-controlled clinical trial. Front Vet Sci 2019; 6: 474
  • 10 Tobias KM, Johnston SA. Veterinary Surgery Small Animal. St. Louis, Mo: Saunders Elsevier; 2012
  • 11 Kon E, Filardo G, Roffi A, Andriolo L, Marcacci M. New trends for knee cartilage regeneration: from cell-free scaffolds to mesenchymal stem cells. Curr Rev Musculoskelet Med 2012; 5 (03) 236-243
  • 12 Huňáková K, Hluchý M, Špaková T. et al. Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador retrievers. Res Vet Sci 2020; 132: 513-520
  • 13 Brondeel C, Pauwelyn G, de Bakker E, Saunders J, Samoy Y, Spaas JH. Review: Mesenchymal stem cell therapy in canine osteoarthritis research: “Experientia docet. Front Vet Sci 2021; 8: 668881
  • 14 Spriet M, Hunt GB, Walker NJ, Borjesson DL. Scintigraphic tracking of mesenchymal stem cells after portal, systemic intravenous and splenic administration in healthy beagle dogs. Vet Radiol Ultrasound 2015; 56 (03) 327-334
  • 15 Barthélémy I, Thibaud JL, de Fornel P. et al. In vivo stem cell tracking using scintigraphy in a canine model of DMD. Sci Rep 2020; 10 (01) 10681
  • 16 Kolecka MA, Arnhold S, Schmidt M. et al. Behaviour of adipose-derived canine mesenchymal stem cells after superparamagnetic iron oxide nanoparticles labelling for magnetic resonance imaging. BMC Vet Res 2017; 13 (01) 62
  • 17 Carré A, Klausner G, Edjlali M. et al. Standardization of brain MR images across machines and protocols: bridging the gap for MRI-based radiomics. Sci Rep 2020; 10 (01) 12340
  • 18 Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JWM. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004; 17 (07) 513-517
  • 19 Bulte JW, Kraitchman DL, Mackay AM, Pittenger MF. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides. Blood 2004; 104 (10) 3410-3412 , author reply 3412–3413
  • 20 Jülke H, Veit C, Ribitsch I, Brehm W, Ludewig E, Delling U. Comparative labeling of equine and ovine multipotent stromal cells with superparamagnetic iron oxide particles for magnetic resonance imaging in vitro. Cell Transplant 2015; 24 (06) 1111-1125
  • 21 Küstermann E, Himmelreich U, Kandal K. et al. Efficient stem cell labeling for MRI studies. Contrast Media Mol Imaging 2008; 3 (01) 27-37
  • 22 Shinohara RT, Sweeney EM, Goldsmith J. et al; Australian Imaging Biomarkers Lifestyle Flagship Study of Ageing, Alzheimer's Disease Neuroimaging Initiative. Statistical normalization techniques for magnetic resonance imaging. Neuroimage Clin 2014; 6: 9-19
  • 23 Simmons A, Tofts PS, Barker GJ, Arridge SR. Sources of intensity nonuniformity in spin echo images at 1.5 T. Magn Reson Med 1994; 32 (01) 121-128
  • 24 Yoo JH, Park C, Jung D-I. et al. In vivo cell tracking of canine allogenic mesenchymal stem cells administration via renal arterial catheterization and physiopathological effects on the kidney in two healthy dogs. J Vet Med Sci 2011; 73 (02) 269-274
  • 25 Lu S-S, Liu S, Zu Q-Q. et al. In vivo MR imaging of intraarterially delivered magnetically labeled mesenchymal stem cells in a canine stroke model. PLoS One 2013; 8 (02) e54963