Rescue of salivary gland function after stem cell transplantation in irradiated glands.

Rescue of salivary gland function after stem cell transplantation in irradiated glands.
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干细胞移植在辐照腺体中的干细胞移植后拯救唾液腺功能。

DOI:
10.1371/journal.pone.0002063
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发表时间:
2008-04-30
期刊:
影响因子:
3.7
通讯作者:
Coppes, Robert P.
Coppes, Robert P.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lombaert, Isabelle M. A.;Brunsting, Jeanette F.;Wierenga, Pieter K.;Faber, Hette;Stokman, Monique A.;Kok, Tineke;Visser, Willy H.;Kampinga, Harm H.;de Haan, Gerald;Coppes, Robert P.

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头颈癌是第五大常见恶性肿瘤,占每年所有新发癌症病例的3%。尽管相对较高的生存率,这些患者的生活质量是严重受损,因为辐射诱导的唾液腺功能的损害和随之而来的口干症(口干综合征)。在这项研究中,一个临床上适用的方法恢复放射损伤的唾液腺功能,唾液腺干细胞移植的发展。唾液腺细胞分离自小鼠下颌下腺,并在体外培养成唾液球,其含有表达干细胞标志物Sca-1、c-Kit和Musashi-1的细胞。在体外培养条件下,细胞可分化为涎腺导管细胞和分泌粘蛋白和淀粉酶的腺泡细胞。使用c-Kit作为标记物通过流式细胞术选择进行干细胞富集。在体外,细胞分化为产生淀粉酶的腺泡细胞。在体内,少量c-Kit+细胞的腺内移植导致唾液腺形态和功能的长期恢复。此外,供者来源的干细胞可以从原代受体中分离,培养为次级球,并在再次移植后改善辐射损伤。我们的方法是第一次证明干细胞移植的潜在用途,以功能拯救唾液腺缺陷。
Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome). In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit+ cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.
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