Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland
Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland
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DOI：
10.1016/j.radonc.2013.05.020
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发表时间：
2013-09-01
影响因子：
5.7
通讯作者：
Coppes, Robert P.
中科院分区：
文献类型：
--
作者：
Nanduri, Lalitha S. Y.;Lombaert, Isabelle M. A.;Coppes, Robert P.
简介：在放射治疗期间，头颈部癌症患者的唾液腺被不可避免地共同照射，可能导致终身损伤。最近，我们发现移植的salisphere-derived c-Kit表达细胞可以功能性再生照射唾液腺。本研究的目的是选择一个更有效的亚群的c-Kit（+）细胞，共表达干细胞标记，并调查是否长期的组织稳态是恢复后干细胞transplantation.Methods和结果：Salphere衍生的c-Kit（+）细胞，共表达CD 24和/或CD 49 f标记，intra-glandularly注射到15戈伊照射小鼠的下颌下腺。特别是，c-Kit（+）/CD 24（+）/CD 49 f（+）细胞移植小鼠与辐照对照组（21.5 +/- 8.7%）相比改善了唾液产生（54.59 +/- 11.1%）。具有分化的导管细胞标记物如细胞角蛋白（CK 8、18、7和14）的细胞的表达增加表明该隔室的功能恢复。此外，导管干细胞标志物表达，如c-Kit，CD 133，CD 24和CD 49 f在移植后再次出现，表明腺体的长期功能维持潜力。此外，正常化的血管化所示的0331的表达和减少纤维化的观察，表明正常化的微environment.Conclusions：我们的研究结果表明，干细胞移植不仅挽救低唾液分泌，但也恢复组织稳态的照射腺，必要的长期维护成人组织。(C)2013爱思唯尔爱尔兰有限公司版权所有。放射治疗和肿瘤学108（2013）458-463
Introduction: During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands. This study aims to select a more potent subpopulation of c-Kit(+) cells, co-expressing stem cell markers and to investigate whether long-term tissue homeostasis is restored after stem cell transplantation.Methods and results: Salisphere derived c-Kit(+) cells that co-expressed CD24 and/or CD49f markers, were intra-glandularly injected into 15 Gy irradiated submandibular glands of mice. Particularly, c-Kit(+)/CD24(+)/CD49f(+) cell transplanted mice improved saliva production (54.59 +/- 11.1%) versus the irradiated control group (21.5 +/- 8.7%). Increase in expression of cells with differentiated duct cell markers like, cytokeratins (CK8, 18,7 and 14) indicated functional recovery of this compartment. Moreover, ductal stem cell marker expression like c-Kit, CD133, CD24 and CD49f reappeared after transplantation indicating long-term functional maintenance potential of the gland. Furthermore, a normalization of vascularization as indicated by 0331 expression and reduction of fibrosis was observed, indicative of normalization of the microenvironment.Conclusions: Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 458-463