Cell Therapy Program, Princess Margaret Cancer Centre and Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Cell Therapy Program, Princess Margaret Cancer Centre and Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Cytotherapy. 2018 Aug;20(8):1001-1012. doi: 10.1016/j.jcyt.2018.05.011. Epub 2018 Jul 31.
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.
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/γ 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.
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.
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.
间充质基质细胞（MSCs）可促进伤口愈合，包括放疗（RT）和手术后的愈合。在恶性肿瘤的再生医学中使用 MSCs，例如在软组织肉瘤（STS）患者中增强 RT/手术后的伤口愈合，需要进行安全性验证。本研究的目的是确定人 MSCs 对 STS 体外生长以及体内局部复发和转移的影响。
将人原发性 STS 和 HT-1080 纤维肉瘤系转导以表达荧光素酶/增强型绿色荧光蛋白（eGFP）。肉瘤细胞与骨髓来源的 MSCs 共培养或共注射以进行生长研究。使用 STS 系在 NOD/SCID/γ 小鼠中建立异种移植肿瘤模型。为了模拟临床情况，在将 MSC 注射到肿瘤床之前，对皮下肿瘤进行 RT/手术治疗。使用组织学和生物发光成像研究局部和远处肿瘤复发。
MSCs 在体外共培养时不会促进 STS 增殖，这在来自不同供体的 MSCs 中是一致的。与单独注射肉瘤细胞的对照小鼠相比，将 MSCs 与肉瘤细胞共注射到小鼠中并没有显著的肿瘤刺激作用。RT/手术后给予 MSC 对 STS 的局部复发或转移没有影响。
这些研究对于确立 STS 患者 MSC 给药的安全性概况非常重要。我们的数据表明，在标准治疗 RT/手术后，MSC 在 STS 管理中是安全的，这可以在早期临床试验中进一步研究，以确定 MSC 在减少发病率和减轻这些患者的伤口并发症方面的疗效。
