Parenchymal/Stem Cell Pathways for Salivary Gland Repair

唾液腺修复的实质/干细胞途径

基本信息

批准号：
6668672
负责人：
ROBERT Shelton REDMAN
金额：
$ 13.26万
依托单位：
INSTITUTE FOR CLINICAL RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2006-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6668672
关键词：
CD34 molecule acinar cell cell differentiation cell proliferation electron microscopy gastrointestinal epithelium hematopoietic stem cells histogenesis laboratory rat method development mixed tissue /cell culture morphology salivary glands sex chromosomes stem cells submandibular gland tissue engineering

项目摘要

DESCRIPTION (provided by applicant): Major loss of salivary gland acinar and other epithelial cells to disease or radiation therapy results in severe curtailment of saliva, causing marked oral discomfort and disease and loss of teeth. The long range objective is to find ways to regenerate gland structures to relieve these problems. Using the rat submandibular gland as a model, we propose to move towards this objective via three approaches. (1) Determine which of the several types of salivary gland cells have the potential to proliferate and redifferentiate into the acini and ducts required to restore gland function. (2) Develop methods to deliver these cells into salivary glands and foster their development into new acini and ducts. (3) Develop conditions for inducing hematopoietic stem cells to differentiate into salivary gland cells in vitro and in vivo, thus providing the potential for an autologous, non-glandular source of cells for delivery into damaged glands. Previously developed primary culture conditions will be refined to produce nearly pure acinar, intercalated duct and larger duct cells, then switched to learn to what extent the cells can re-differentiate in vitro. Dispersed salivary acinar or ductal cells from male rats will be seeded into salivary glands of female rats by infusion into the main duct with enough pressure to leak into the stroma, or by injection into the gland, and followed via their Y chromosomes for proliferation and differentiation in situ. Hematopoetic stem cells from male rats will be collected and tested for salivary differentiation in co-culture with female salivary gland cells or seeded in situ as above, also using the Y chromosome to mark stem cells and their progeny.

描述（由申请人提供）：由于疾病或放射治疗，唾液腺腺泡和其他上皮细胞大量丧失，导致唾液严重减少，导致明显的口腔不适和疾病以及牙齿脱落。长期目标是找到再生腺体结构的方法来缓解这些问题。使用大鼠颌下腺作为模型，我们建议通过三种方法实现这一目标。 (1) 确定几种类型的唾液腺细胞中哪一种具有增殖和再分化为恢复腺体功能所需的腺泡和导管的潜力。 (2) 开发将这些细胞输送到唾液腺并促进它们发育成新的腺泡和导管的方法。 (3) 开发在体外和体内诱导造血干细胞分化为唾液腺细胞的条件，从而为将自体非腺体细胞来源输送到受损腺体提供潜力。先前开发的原代培养条件将被改进，以产生近乎纯的腺泡、闰管和更大的导管细胞，然后转而研究细胞在体外可以重新分化的程度。将雄性大鼠分散的唾液腺泡或导管细胞接种到雌性大鼠的唾液腺中，方法是在足够的压力下输注到主导管中以渗漏到基质中，或注射到腺体中，然后通过其Y染色体进行增殖和分化原地。将收集雄性大鼠的造血干细胞，并与雌性唾液腺细胞共培养或原位接种，测试其唾液分化，同时使用 Y 染色体标记干细胞及其后代。