Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery |
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Authors: | PAOLA A FILOMENO KYUNG-PHIL KIM NARA YOON IRAN RASHEDI VICTOR DAYAN RITA A KANDEL XING-HUA WANG TANIA C FELIZARDO ELLIOT BERINSTEIN SALOMEH JELVEH ANDREA FILOMENO JEFFREY A MEDIN PETER C FERGUSON ARMAND KEATING |
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Institution: | 1. Cell Therapy Program, Princess Margaret Cancer Centre and Krembil Research Institute, University Health Network, Toronto, Ontario, Canada;2. Pathology and Lab Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada;3. Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;4. Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada;5. University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada |
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Abstract: | Background. Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. Methods. Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow–derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γcnull mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. Results. MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. Discussion. These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients. |
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Keywords: | human mesenchymal stromal cells regenerative medicine soft tissue sarcoma tumor xenograft model wound healing |
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