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Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints

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Abstract

Purpose

While imaging matrix-associated stem cell transplants aimed for cartilage repair in a rodent arthritis model, we noticed that some transplants formed locally destructive tumors. The purpose of this study was to determine the cause for this tumor formation in order to avoid this complication for future transplants.

Procedures

Adipose-derived stem cells (ADSC) isolated from subcutaneous adipose tissue were implanted into 24 osteochondral defects of the distal femur in ten athymic rats and two immunocompetent control rats. All transplants underwent serial magnetic resonance imaging (MRI) up to 6 weeks post-transplantation to monitor joint defect repair. Nine transplants showed an increasing size over time that caused local bone destruction (group 1), while 11 transplants in athymic rats (group 2) and 4 transplants in immunocompetent rats did not. We compared the ADSC implant size and growth rate on MR images, macroscopic features, histopathologic features, surface markers, and karyotypes of these presumed neoplastic transplants with non-neoplastic ADSC transplants.

Results

Implants in group 1 showed a significantly increased two-dimensional area at week 2 (p = 0.0092), 4 (p = 0.003), and 6 (p = 0.0205) compared to week 0, as determined by MRI. Histopathological correlations confirmed neoplastic features in group 1 with significantly increased size, cellularity, mitoses, and cytological atypia compared to group 2. Six transplants in group 1 were identified as malignant chondrosarcomas and three transplants as fibromyxoid sarcomas. Transplants in group 2 and immunocompetent controls exhibited normal cartilage features. Both groups showed a normal ADSC phenotype; however, neoplastic ADSC demonstrated a mixed population of diploid and tetraploid cells without genetic imbalance.

Conclusions

ADSC transplants can form tumors in vivo. Preventive actions to avoid in vivo tumor formations may include karyotyping of culture-expanded ADSC before transplantation. In addition, serial imaging of ADSC transplants in vivo may enable early detection of abnormally proliferating cell transplants.

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Acknowledgments

The authors would like to acknowledge the imaging support provided by the Stanford Small Animal Imaging Facility (SCI3).

Funding

This work was supported by NIH grant 2R01AR054458 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (PI Daldrup-Link).

Author information

Author notes

  1. Fanny Chapelin and Aman Khurana contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Rm 1665, Stanford, CA, 94305-5654, USA

    Fanny Chapelin, Aman Khurana, Mohammad Moneeb, Hossein Nejadnik & Heike E. Daldrup-Link

  2. Department of Pathology, Stanford University, Stanford, CA, USA

    Florette K. Gray Hazard & Dita Gratzinger

  3. BD biosciences, Custom Technology Team, La Jolla, CA, USA

    Chun Fai Ray Chan & Amitabh Gaur

  4. Department of Communication and Statistics, Stanford, CA, USA

    Solomon Messing

  5. Department of Cytogenetics, Stanford University, Stanford, CA, USA

    Jason Erdmann

  6. Innovative Assay Solutions, San Diego, CA, 92129, USA

    Amitabh Gaur

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  1. Fanny Chapelin
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Correspondence to Heike E. Daldrup-Link.

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Chapelin, F., Khurana, A., Moneeb, M. et al. Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints. Mol Imaging Biol 21, 95–104 (2019). https://doi.org/10.1007/s11307-018-1218-7

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