Bioprocess Development for the Large Scale Production and Differentiation of Adult Human Stem Cells

成人身体中的每个组织都由大量专门的细胞组成，这些细胞执行与该组织相关的功能。越来越多的证据表明，在这些特化细胞中，每个组织中都有非常稀少的成体干细胞。人们认为，这些成体干细胞的作用是通过用新的健康的特化细胞取代因正常磨损或损伤而死亡的特化细胞，使组织在一生中保持适当的工作状态。这种非凡的再生能力意味着成人干细胞可以用来更好地了解正常的发育和愈合，测试新的药物，了解衰老，获得关于某些癌症的知识，甚至开发可以改善人类健康和福祉的新疗法。然而，基于干细胞的新应用的开发受到阻碍，因为研究人员没有足够数量的干细胞来研究。它们在成人组织中的出现频率非常低，这意味着不能简单地分离出足够数量的它们来进行研究。解决这个问题的一种方法是开发强大而有效的方法，鼓励可以从组织中分离的少量干细胞在体外重复分裂(即在培养时)，从而产生大量细胞，研究人员可以利用这些细胞开展他们的工作。传统的在小型培养皿中培养细胞的方法是人工密集和低效的，并且不能支持以可重复的方式大规模生产干细胞。最近，有研究表明，生物反应器是可以仔细监测和控制环境的较大容器，可以用来支持成体干细胞高效和可重复的生长。这里描述的研究计划的重点是更好地了解成体干细胞在培养中的行为，并利用这些信息来设计和优化新的方法和技术，以支持在生物反应器中的受控条件下大规模生产它们。这项研究计划产生的细胞群体将促进新的和重要的成体干细胞应用的发展。

Each tissue in the adult human body is composed of large numbers of specialized cells that carry out the functions associated with that tissue. There is increasing evidence that within each tissue, amongst those many specialized cells, is a very sparse population of adult stem cells. It is believed that the role of these adult stem cells is to maintain tissues in proper working order over the lifetime of an individual by replacing specialized cells which die due to normal wear and tear, or injury, with new healthy specialized cells. This remarkable regenerative capability means that adult stem cells could be used to better understand normal development and healing, test new pharmaceuticals, learn about aging, gain knowledge about certain cancers, and even develop new therapies which could improve human health and wellbeing. However, the development of new stem cell based applications is hampered because researchers do not have adequate quantities of stem cells with which to work. Their very low frequency in adult tissues means they cannot simply be isolated in sufficient numbers for study. One way to address this problem would be to develop robust and efficient methods which encourage the small numbers of stem cells which can be isolated from a tissue, to repeatedly divide outside the body (i.e. when placed in culture), thereby resulting in huge numbers of cells which could be used by researchers to carry out their work. Conventional methods of growing cells in small culture dishes are manually intensive and inefficient, and not able to support the large scale production of stem cells in a reproducible manner. More recently, it has been shown that bioreactors, which are larger vessels in which the environment can be carefully monitored and controlled, can be used to support the efficient and reproducible growth of adult stem cells. The focus of the research program described here is to better understand adult stem cell behaviour in culture, and to use that information to engineer and optimize new methods and technologies which support their large scale production under controlled conditions in bioreactors. The cell populations generated as a result of this research program will facilitate the development of new and important adult stem cell applications.