Molecular Imaging and Biology

, Volume 21, Issue 1, pp 95–104 | Cite as

Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints

  • Fanny Chapelin
  • Aman Khurana
  • Mohammad Moneeb
  • Florette K. Gray Hazard
  • Chun Fai Ray Chan
  • Hossein Nejadnik
  • Dita Gratzinger
  • Solomon Messing
  • Jason Erdmann
  • Amitabh Gaur
  • Heike E. Daldrup-LinkEmail author
Research Article



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.


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.


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.


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.

Key words

Magnetic resonance imaging Stem cell therapy Chondrosarcomas Fibromyxoid sarcomas Osteochondral transplants Malignant tumors in vivo 



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


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

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11307_2018_1218_MOESM1_ESM.pdf (165 kb)
ESM 1 (PDF 164 kb)


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Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  • Fanny Chapelin
    • 1
  • Aman Khurana
    • 1
  • Mohammad Moneeb
    • 1
  • Florette K. Gray Hazard
    • 2
  • Chun Fai Ray Chan
    • 3
  • Hossein Nejadnik
    • 1
  • Dita Gratzinger
    • 2
  • Solomon Messing
    • 4
  • Jason Erdmann
    • 5
  • Amitabh Gaur
    • 3
    • 6
  • Heike E. Daldrup-Link
    • 1
    Email author
  1. 1.Department of Radiology, Molecular Imaging Program at Stanford (MIPS)Stanford UniversityStanfordUSA
  2. 2.Department of PathologyStanford UniversityStanfordUSA
  3. 3.BD biosciences, Custom Technology TeamLa JollaUSA
  4. 4.Department of Communication and StatisticsStanfordUSA
  5. 5.Department of CytogeneticsStanford UniversityStanfordUSA
  6. 6.Innovative Assay SolutionsSan DiegoUSA

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