Manipulating Stem Cells to Provide Long Term Regeneration of Irradiated Salivary Glands

项目总结/摘要 在世界范围内，每年有超过50万幸存的头颈癌患者的生活质量受到影响。 由于健康唾液分泌唾液腺的共同照射而急剧降低。目前的治疗方法， 抢救唾液分泌不足只能提供暂时缓解;因此， needed.在小鼠模型中，我们通过移植KIT+ 干/祖细胞。然而，这种干/祖细胞群体随着年龄的增长而减少， 因此，目前损害了我们有效使用这些细胞进行治疗的能力。最近 我们实验室的发现表明，转录因子SOX 10密切调节增殖， 胎儿KIT+细胞的分化。在这个提议中，我们假设只有一个成人KIT+细胞亚群， 其表达SOX 10，保留干细胞自我更新能力。因此，我们的目标是：（1）刻画多能 KIT+细胞群中的干细胞，（2）定义转录因子SOX 10在维持成体干细胞中的作用 KIT+细胞，和（3）表征人KIT+细胞中的分子异质性和SOX 10特征。 总的来说，这里提出的科学思想将扩大我们对唾液腺干细胞群体的了解， 并且将通过基于干细胞的疗法显著改善未来的唾液分泌不足的挽救。

PROJECT SUMMARY/ABSTRACT Worldwide, the quality of life of over half a million surviving head-and-neck cancer patients per year is drastically decreased due to co-irradiation of healthy saliva-secreting salivary glands. Current therapies to rescue hypo-salivation only provide temporary relief; hence new therapies for permanent tissue repair are needed. In a mouse model, we induced successful repair of irradiated salivary glands by transplanting KIT+ stem/progenitor cells. However, this population of stem/progenitor cells decreases with age and is heterogeneous; hence, currently compromising our ability to efficiently use these cells for therapy. Recent discoveries in our lab have shown that transcription factor SOX10 tightly regulates proliferation and differentiation in fetal KIT+ cells. In this proposal we hypothesize that only a subpopulation of adult KIT+ cells, which express SOX10, retain stem cell self-renewal capacity. Thus, we aim to: (1) characterize the multipotent stem cells within the KIT+ cell population, (2) define the role of transcription factor SOX10 in maintaining adult KIT+ cells, and (3) characterize the molecular heterogeneity and SOX10 signature in human KIT+ cells. Overall, the scientific ideas proposed here will expand our knowledge of salivary gland stem cell populations, and will significantly improve future hypo-salivation rescuing by stem cell-based therapies.