Enrichment, differentiation and functional analysis of Growth Hormone progenitor cells from the adult mouse pituitary

许多重要的身体机能，包括生长、新陈代谢、青春期的开始、生育、哺乳和应对压力的能力，都是由脑下垂体分泌的激素控制的。因此，垂体激素分泌不足（垂体功能低下）会导致危及生命的疾病，这是一个重要的临床问题。生长激素（GH）缺乏症是垂体激素缺乏症最常见的形式，影响1:3500人。目前，生长激素缺乏症的治疗方法是每天注射生长激素，每位患者每年的费用为3万至5万美元。然而，即使每天注射，尽管成本很高，也很难模仿体内自然波动的激素水平，导致不完全的生长恢复。长期注射也有严重的副作用，可能导致心血管问题、骨密度异常、糖尿病和各种癌症。为了克服激素疗法的缺点，我们正在研究一种新的细胞替代疗法来治疗生长激素缺乏症。这种方法需要了解gh分泌细胞在成人垂体中产生和维持的机制。我们首次从成年小鼠垂体中分离出一种能够分裂并产生gh分泌细胞的祖细胞（未特化）。我们目前的研究旨在进一步纯化这些细胞，并表明它们能够分泌生长激素以响应生物学相关信号。此外，我们将测试这些细胞是否能在小鼠体内生长并发育成功能细胞。特别是，我们将测试祖细胞是否可以用生长激素缺乏的小鼠模型来拯救侏儒症。这项开创性的研究将首次深入了解垂体细胞治疗的可能性，并可能最终导致GH缺乏症患者更好的治疗方法的发展。

Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH deficiency is treated by daily injections of growth hormone at a cost of $30,000 to $50,000 per patient per annum. However, even with daily injections and despite the cost, it is difficult to mimic the naturally fluctuating hormone levels in the body, resulting in incomplete growth rescue. Long term injections also have severe side effects that can lead to cardiovascular problems, abnormal bone density, diabetes and cancers of various types. To overcome the disadvantages of hormone therapy we are investigating a new cell replacement therapy to treat GH deficiency. This approach requires knowledge about the mechanism by which GH-secreting cells are generated and maintained in the adult pituitary. For the first time, we have isolated a type of progenitor (unspecialised) cell from adult mouse pituitary that is capable of dividing and generating GH-secreting cells. Our current research aims to further purify these cells and to show that they are capable of secreting GH in response to biologically relevant signals. In addition, we will test whether these cells can grow and develop into functional cells when introduced into mice. In particular, we will test whether the progenitor cells can rescue dwarfism using a mouse model of GH deficiency. This pioneering study will provide the first insight into the possibility of cell therapy for the pituitary, and may ultimately lead to the development of better therapies for patients with GH deficiency.