Allogeneic multipotent mesenchymal stromal cell sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones
Allogeneic multipotent mesenchymal stromal cell sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones
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DOI：
10.1016/j.reth.2018.10.008
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发表时间：
2019-06-01
影响因子：
4.3
通讯作者：
Ando, Tomohiro
中科院分区：
文献类型：
--
作者：
Kaibuchi, Nobuyuki;Iwata, Takanori;Ando, Tomohiro
前言：双磷酸盐相关性颌骨坏死(BRONJ)是一种难治性疾病，已有多例报道。一般静脉注射多能间充质基质细胞(MSCs)治疗BRONJ可能是有效的，但也存在一些严重的问题。因此，我们的目标是开发一种局部应用MSCs的治疗方法。在本研究中，我们观察了含唑来膦酸盐和地塞米松的Beagle犬MSC片移植对下颌骨愈合的影响。方法：将从皮下脂肪中分离的MSCs接种于温敏培养皿中，制备MSC片。用唑来膦酸盐和地塞米松给比格犬灌胃。然后摘除部分下颌骨皮质骨，移植MSC片覆盖骨缺损区(MSC片移植侧)或非缺损区(对照侧)。结果：术后4周，3只犬中有2只的对侧黏膜创面出现红肿。相比之下，所有狗的MSC片移植侧的粘膜伤口完全愈合。组织学结果显示，对照侧颌骨表面可见大量组织蛋白酶K阳性的多核细胞。结论：MSC片状移植可促进佐来磷酸钠和地塞米松所致犬下颌骨创面的健康愈合。而用唑来膦酸盐和地塞米松治疗的犬下颌骨损伤显示出类似BRONJ的结果。(C)2019年，日本再生医学学会。爱思唯尔B.V.制作和主办。
Introduction: Many cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is an intractable disease, have been reported. Although a general intravenous injection of multipotent mesenchymal stromal cells (MSCs) may be effective for treating BRONJ, it has some severe problems. Therefore, our aim was to develop a treatment of locally administered MSCs. In this study, we investigated the effect of MSC sheet transplantation in the mandibular bone healing in beagle dogs, which were administered zoledronate and dexamethasone.Methods: MSCs isolated from subcutaneous fat were seeded onto temperature-responsive culture dishes to produce MSC sheets. Zoledronate and dexamethasone were administered to beagle dogs. Then, the parts of mandibular cortical bones were removed, and MSC sheets were transplanted to cover those bone defects (MSC sheet transplant side) or not (Control side). The specimens were evaluated in micro CT, histology, and immunohistochemistry.Results: Four weeks after surgery, redness and swellings were observed in the mucosal wounds of the control sides of 2 of 3 dogs. In contrast, the mucosal wounds of the MSC sheet transplant sides of all dogs completely healed. Histological images showed some free sequestrums and many bacterial colonies, and Immunohistological analysis showed some cathepsin K-positive multinuclear cells detached from jaw bone surfaces in the control sides.Conclusions: MSC sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones. And the injured canine mandibular bones administered zoledronate and dexamethasone showed BRONJ-like findings. (C) 2019, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.