Adrenal Cortical Cell Therapy

描述(由申请人提供)： 我的长期职业目标是拥有一个学术职位，让我能够进行再生医学的研究，治疗患有外科疾病的婴儿和儿童，并在实验室和临床病房教授内科和研究生。 我的短期职业目标是获得干细胞分子生物学方面的新技能和知识。研究生涯发展计划包括实验室工作、指导和分子遗传学和干细胞生物学的精选课程。我选择了加州大学洛杉矶分校和我的导师爱德华·麦凯布博士，因为他在人类遗传学和肾上腺发育的分子机制方面的专业知识，大学的资源，以及儿科和外科承诺支持我的培训。在科学咨询委员会的指导下，我将在培训期结束前过渡成为一名独立调查员。 这项拟议的研究侧重于将肾上腺皮质细胞分类为由其细胞表面标记定义的亚群。用在肾上腺皮质细胞中表达绿色荧光蛋白的转基因小鼠作为动物模型。在具体目标1中，将使用三组表面标记来使用荧光激活细胞分选将肾上腺皮质细胞分离为亚群。他们的肾上腺特异的mRNA图谱将通过实时荧光聚合酶链式反应来确定。在特定的目标2中，根据肾上腺皮质细胞表面标志物的差异表达而分类的亚群将被移植到肾被膜下，以确定它们的再生潜力。再生的组织将被评估其支持肾上腺皮质功能的能力。这些研究将有助于更好地了解肾上腺皮质的发育，以及取代肾上腺皮质生理功能的新疗法。

DESCRIPTION (provided by applicant): My long-term career goal is to have an academic position that allows me to conduct research in regenerative medicine, to treat infants and children with surgical disorders, and to teach medical and graduate students in the laboratory and on the clinical ward. My short-term career goal is to acquire new skills and knowledge in stem cell molecular biology. The research career development plan includes laboratory work, mentoring, and selected courses in molecular genetics and stem cell biology. I have chosen UCLA and my mentor, Dr. Edward McCabe, because of his expertise in human genetics and molecular mechanisms of adrenal development, the resources of the university, and the commitment of the Departments of Pediatrics and Surgery to support my training. Under the guidance of the Scientific Advisory Committee, I will make the transition to become an independent investigator by the end of the training period. The proposed research is focused on sorting adrenal cortical cells into subpopulations as defined by their cell surface markers. A transgenic mouse that expresses the green fluorescent protein in adrenal cortical cells is used as the animal model. In Specific Aim 1, three sets of surface markers will be employed to separate adrenal cortical cells into subpopulations using fluorescence activated cell sorting. Their adrenal-specific mRNA profiles will be determined by real-time PCR. In Specific Aim 2, subpopulations of adrenal cortical cells sorted on the basis of their differential expression of surface markers will be transplanted under the renal capsule to determine their regenerative potential. The regenerated tissues will be evaluated for their ability to support adrenal cortical function. These studies will lead to a better understanding of the development of the adrenal cortex, as well as a new therapy that replaces the physiological function of the adrenal cortex.