Fluorescence molecular tomography of DiR-labeled mesenchymal stem cell implants for osteochondral defect repair in rabbit knees

Markus T. Berninger, Pouyan Mohajerani, Melanie Kimm, Stephan Masius, Xiaopeng Ma, Moritz Wildgruber, Bernhard Haller, Martina Anton, Andreas B. Imhoff, Vasilis Ntziachristos, Tobias D. Henning, Reinhard Meier

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Objectives: To assess labelling efficiency of rabbit mesenchymal stem cells (MSCs) using the near-infrared dye 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindotricarbocyanine iodide (DiR) and detection of labelled MSCs for osteochondral defect repair in a rabbit model using fluorescence molecular tomography–X-ray computed tomography (FMT-XCT). Methods: MSCs were isolated from New Zealand White rabbits and labelled with DiR (1.25-20 μg/mL). Viability and induction of apoptosis were assessed by XTT- and Caspase-3/-7-testing. Chondrogenic potential was evaluated by measurement of glycosaminoglycans. Labelled cells and unlabeled controls (n = 3) underwent FMT-XCT imaging before and after chondrogenic differentiation. Osteochondral defects were created surgically in rabbit knees (n = 6). Unlabeled and labelled MSCs were implanted in fibrin-clots and imaged by FMT-XCT. Statistical analyses were performed using multiple regression models. Results: DiR-labelling of MSCs resulted in a dose-dependent fluorescence signal on planar images in trans-illumination mode. No significant reduction in viability or induction of apoptosis was detected at concentrations below 10 μg DiR/mL (p >.05); the chondrogenic potential of MSCs was not affected (p >.05). FMT-XCT of labelled MSCs in osteochondral defects showed a significant signal of the transplant (p <.05) with additional high-resolution anatomical information about its osteochondral integration. Conclusions: FMT-XCT allows for detection of stem cell implantation within osteochondral regeneration processes. Key Points: • DiR-labelling of MSCs shows no toxic side effects or impairment of chondrogenesis. • Fluorescence molecular tomography allows for detection of MSCs for osteochondral defect repair. • FMT-XCT helps to improve evaluation of cell implantation and osteochondral regeneration processes.

Original languageEnglish
Pages (from-to)1105-1113
Number of pages9
JournalEuropean Radiology
Volume27
Issue number3
DOIs
StatePublished - 1 Mar 2017
Externally publishedYes

Keywords

  • Cell labelling
  • Fluorescence molecular imaging
  • Mesenchymal stem cells
  • Osteochondral
  • Rabbit

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