Mol Imaging Biol (2018)
* World Molecular Imaging Society, 2018
Tumor Formation of Adult Stem Cell Transplants
in Rodent Arthritic Joints
Florette K. Gray Hazard,
Chun Fai Ray Chan,
Heike E. Daldrup-Link
Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Rm 1665, Stanford, CA,
Department of Pathology, Stanford University, Stanford, CA, USA
BD biosciences, Custom Technology Team, La Jolla, CA, USA
Department of Communication and Statistics, Stanford, CA, USA
Department of Cytogenetics, Stanford University, Stanford, CA, USA
Innovative Assay Solutions, San Diego, CA, 92129, USA
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.
Fanny Chapelin and Aman Khurana contributed equally to this work.
Electronic supplementary material The online version of this article (https://
doi.org/10.1007/s11307-018-1218-7) contains supplementary material,
which is available to authorized users.
Correspondence to: Heike Daldrup-Link; e-mail: H.E.Daldrup-