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04.06.2018 | Research Article

Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints

verfasst von: 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-Link

Erschienen in: Molecular Imaging and Biology | Ausgabe 1/2019

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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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Titel: Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints
verfasst von: 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-Link
Publikationsdatum: 04.06.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 1/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1218-7

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Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints