Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints.

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...

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Publicado en:Molecular Imaging & Biology Vol. 21; no. 1; pp. 95 - 105
Autores principales: Chapelin, Fanny, Khurana, Aman, Moneeb, Mohammad, Gray Hazard, Florette K., Chan, Chun Fai Ray, Nejadnik, Hossein, Gratzinger, Dita, Messing, Solomon, Erdmann, Jason, Gaur, Amitabh, Daldrup-Link, Heike E.
Formato: Journal Article
Publicado: Springer Nature Feb2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2019
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-018-1218-7
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        atl: Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints.
      aug:
        au:
          Chapelin, Fanny
          Khurana, Aman
          Moneeb, Mohammad
          Gray Hazard, Florette K.
          Chan, Chun Fai Ray
          Nejadnik, Hossein
          Gratzinger, Dita
          Messing, Solomon
          Erdmann, Jason
          Gaur, Amitabh
          Daldrup-Link, Heike E.
        affil: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Rm 1665, 94305-5654, Stanford, CA, USA
      sug:
        subj:
          Stem Cells Transplantation
          Cell Transformation, Neoplastic Pathology
          Arthritis Therapy
          Neoplasms, Fibrous Tissue Etiology
          Chondrosarcoma Etiology
          Femur Pathology
          Rats
          Rodents
          Joints Pathology
          Bone Neoplasms Pathology
          Chondrosarcoma Pathology
          Neoplasms, Fibrous Tissue Diagnosis
          Animals
          Stem Cells Pathology
          Bone Neoplasms Etiology
          Arthritis Pathology
          Neoplasms, Fibrous Tissue Pathology
          Arthritis Diagnosis
          Cells, Cultured
          Joints
          Chondrosarcoma Diagnosis
          Femur
          Male
          Magnetic Resonance Imaging
          Bone Neoplasms Diagnosis
          Arthritis Impact Measurement Scales
          Male
      ab: 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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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