MR Signal Characteristics of Viable and Apoptotic Human Mesenchymal Stem Cells in Matrix-Associated Stem Cell Implants for Treatment of Osteoarthritis

Department of Radiology and Biomedical Imaging, UCSF Medical Center, University of California, San Francisco, CA 94143, USA.
Investigative radiology (Impact Factor: 4.44). 10/2010; 45(10):634-40. DOI: 10.1097/RLI.0b013e3181ed566c
Source: PubMed


To compare magnetic resonance (MR) signal characteristics of contrast agent-labeled apoptotic and viable human mesenchymal stem cells (hMSCs) in matrix-associated stem cell implants.
hMSCs were labeled with Food and Drug Administration-approved ferumoxides nanoparticles. One group (A) remained untreated whereas a second group (B) underwent mitomycin C-induced apoptosis induction. Viability of group A and apoptosis of group B was confirmed by caspase-assays and terminal dUTP nick-end labeling (TUNEL) stains. Labeled viable hMSCs, unlabeled viable hMSCs, labeled apoptotic hMSCs, and unlabeled apoptotic hMSCs (n = 7 samples each) in an agarose scaffold were implanted into cartilage defects of porcine patellae specimens and underwent MR imaging at 7 T, using T1-weighted spin-echo sequences, T2-weighted spin-echo sequences, and T2*-weighted gradient-echo sequences. Signal-to-noise ratios (SNR) of the implants were calculated and compared between different experimental groups using linear mixed regression models.
Ferumoxides-labeled hMSCs provided a strong negative T2 and T2*-enhancement. Corresponding SNR data of labeled hMSCs were significantly lower compared with unlabeled controls (P < 0.05). Apoptosis induction resulted in a significant signal decline of ferumoxides-labeled hMSC transplants on short echo time T2-weighted spinecho sequences. SNR data of labeled apoptotic hMSCs were significantly lower compared with labeled viable hMSCs (P < 0.05).
Apoptosis of transplanted ferumoxides-labeled stem cells in cartilage defects can be visualized noninvasively by a significant signal decline on T2-weighted MR images. The described MR signal characteristics may serve as a noninvasive outcome measure for the assessment of matrix-associated stem cell implants in clinical practice. Additional studies are needed to further enhance the observed differences between viable and apoptotic cells, for example, by further optimizing the applied MR pulse sequence parameters or intracellular contrast agent concentration.

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    • "Our studies have shown that viable and apoptotic MASI demonstrate distinct signal characteristics on MR images, when the cells are labeled with iron oxide nanoparticles [15,36,37,48]. Iron oxide labeled viable MASI demonstrated an increasing area of T2-signal loss in the early post-transplant period (1-2 weeks post MASI), which correlated to stem cell expansion over a larger areaat the transplantation site. "
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    • "Among various available imaging techniques for cell tracking [12], [13], [14], MR imaging has the distinct advantages of providing direct cartilage depiction with high anatomical resolution, high soft tissue contrast and no radiation exposure. In previous studies, stem cells were labeled with superparamagnetic iron oxide nanoparticles (SPIO) for their direct depiction in cartilage defects with MR imaging [15], [16], [17]. SPIO allow for cell labeling by simple incubation. "
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