Podium Presentation Animal Models

18.3.2 - In vivo MRI cell tracking of autologous mesenchymal stem cells in an ovine osteochondral defect model.

Presentation Number
18.3.2
Presentation Topic
Animal Models
Lecture Time
14:24 - 14:33
Session Type
Free Papers
Corresponding Author
  • A. El Haj (Birmingham, GB)
Authors
  • H. Markides (Birmingham, GB)
  • K. Newell (Cambridge, GB)
  • H. Rudorf (Cambridge, GB)
  • L. L. Blokpoel Ferreras (Nottingham, GB)
  • J. Dixon (Nottingham, GB)
  • M. Graves (Cambridge, GB)
  • J. Kaggie (Cambridge, GB)
  • F. Henson (Cambridge, GB)
  • A. El Haj (Birmingham, GB)

Abstract

Purpose

We aim to devise and implement a SPION (superparamagnetic iron oxide nanoparticle) based technique to non-invasively monitor the intra-articular delivery and bio-distribution of stem cells within a knee joint by MR-imaging. Osteochondral injuries represent a significant clinical problem requiring cell-based therapies to restore function of the damaged joint. Pre-clinical studies are fundamental in translating such therapies, however, technologies to non-invasively assess in vivo cell fate are currently limited. We implement this technique to monitor and compare in vivo cell fate in a pre-clinical ovine model of a chronic and an acute osteochondral injury.

Methods and Materials

Autologous ovine MSCs were isolated, expanded and labelled with Nanomag using the cell-penetrating peptide, P218R. In vitro and ex vivo MRI detection thresholds and cellular viability, proliferation and differentiation were determined prior to in vivo studies. A single 8mm diameter osteochondral defect was created in the medial femoral condyle in the left knee joint of each sheep with the contralateral joint serving as the control. 10x106 Nanomag labelled-MSCs were delivered by intra-articular injection at 1 week or 4.5 weeks post injury. Sheep were sacrificed 7 days post implantation and immediately MR imaged using an ESAOTE 0.2T and Siemens 3T scanner and prior to histological assessement.

Results

In vitro MRI data demonstrated significant increase in MRI contrast as a result of P218R:Nanomag with no impairment of cell function. MRI images revealed evidence of implanted cells within the synovial joint of the injured leg of the chronic model only with no signs of cell localisation to the defect site in either model. This was validated histologically determining the location of implanted cells in the synovium with evidence of engulfment of Nanomag-labelled cells by leukocytes.

Conclusion

We demonstrates the potential of Nanomag and P218R as an effective means of imaging and tracking cells within the knee.

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