Human Developmental Biology Resource (HDBR): meeting new trends and challenges in developmental biobanking

了解出生前胚胎和胎儿的发育是很重要的，不仅可以正确地认识我们从受精卵开始的起源，还可以深入了解出生前或出生前出现的许多疾病。一些儿童后期或成人疾病也受到胎儿期的强烈影响。尽管如此，我们对人类的发展知之甚少，而对其他动物的发展却知之甚少，包括老鼠、鸡、鱼，甚至果蝇。现在，通过对终止妊娠后获得的胚胎和胎儿组织的研究，解决了这一关于人类发育的贫乏知识水平。人类发育生物学资源（HDBR）通过向科学家提供来自这些样本的材料，使这项重要的研究成为可能。HDBR已获得伦理和人类组织管理局的批准，可以收集、储存和分发用于研究的人类胎儿材料。这些材料是在妇女接受专业咨询并决定终止妊娠后，经知情同意获得的。对这些样本进行发育阶段评估，并进行测试，以确定它们的基因是否正常。然后，这些组织要么立即送到研究人员那里培养组织/细胞，要么提取生物分子，要么将样本冷冻或以其他方式保存，以便以后分发给研究人员。样本的详细信息被记录在一个匿名的安全数据库中，因此与捐赠妇女没有联系。HDBR还提供“研究服务”，HDBR工作人员代表科学家对人体材料进行研究工作。迄今为止，已有600多个不同的研究项目收到了HDBR的材料，这导致了近400篇科学论文的发表。下一阶段HDBR工作的目标有几个方面。我们将发展“研究诊所”，邀请妇女在医院而不是像目前的保健服务趋势那样在家里完成终止妊娠。这将确保HDBR能够继续收集最早的胚胎阶段，这对于理解器官最初是如何形成的至关重要。我们还将组织收集扩展到胎儿后期和新生儿时期，这一时期迫切需要研究，但样本很少。我们将与科学家合作，确保为研究提供哪怕是胎儿最小、最难以接触到的部分。我们将扩大对异常样本的收集，例如因唐氏综合症或其他严重胎儿问题而终止妊娠的样本。我们将建立HDBR研究服务的新部分，称为空间转录组学，其中基因的表达可以直接在胎儿组织中进行研究。我们还将扩大HDBR地图集，这是一个可供公众获取有关人类发展信息的网站。这项人类发育研究的最终目的是更好地了解出生缺陷，出生缺陷发生在3%的怀孕中，造成20%的婴儿死亡。这包括脊柱裂、心脏穿孔和唇腭裂等疾病，这些疾病往往会给儿童带来终身的医疗问题，给家庭带来照顾方面的挑战，并给卫生服务带来相当大的经济负担。虽然可以选择终止妊娠，但最终目的是了解胚胎和胎儿的出生缺陷是如何发展的，以便提供预防措施。这些可能涉及像叶酸这样的重要营养素，或者干细胞移植，这对未来的疾病治疗有很大的希望。研究人员越来越多地发现与这些疾病相关的基因被破坏，这增加了将来提供遗传咨询和基因治疗的可能性。所有这些医学上的进步都将通过对人类胚胎和胎儿如何发育的更好理解而更容易实现。

Understanding how the embryo and fetus develop before birth is important, not only to properly appreciate our origins from the fertilised egg, but also to gain insight into the many diseases that arise before or around the time of birth. Some later childhood or adult diseases also have strong influences from the fetal period. Despite this, we understand rather little about human development and much more about the development of other animals, including the mouse, chicken, fish and even the fruit fly. This poor level of knowledge about human development is now being tackled through studies of tissues from embryos and fetuses, which are obtained after termination of pregnancy. The Human Developmental Biology Resource (HDBR) enables this vital research by providing scientists with access to material from these samples. The HDBR has ethical and Human Tissue Authority approval to collect, store and distribute human fetal material for research. The material is obtained, with informed consent, after the woman has received professional counselling and decided to terminate her pregnancy. The samples are assessed for developmental stage and tested to determine whether they are genetically normal. The tissues are then either immediately sent to researchers to either culture the tissue/cells or to extract the biological molecules, or else the samples are frozen or otherwise preserved for later distribution to researchers. Sample details are recorded on a secure database that is anonymized, so no link to the donating women exists. HDBR also provides a 'research service' where HDBR staff perform research work on the human material on behalf of scientists. To date, over 600 different research projects have received material from the HDBR, and this has led to nearly 400 scientific papers being published.The goals for the next phase of HDBR work are several-fold. We will develop 'research clinics' in which women are invited to complete their pregnancy termination in hospital, rather than at home as is the current health service trend. This will ensure that the HDBR can continue to collect the earliest embryonic stages, which are vital for understanding how organs are first formed. We will also extend tissue collection into the later fetal and newborn periods, where research is urgently needed but samples are rarely available. We will work with scientists to ensure that even the smallest and most hard-to-access parts of the fetus are provided for research. We will extend our collection of abnormal samples, for example from pregnancies that are terminated because of Down Syndrome, or other serious fetal problems. We will establish a new part of the HDBR research service, called Spatial Transcriptomics, in which the expression of genes can be studied directly in the fetal tissues. We will also expand the HDBR Atlas, a publicly available web site where information can be obtained about human development.The eventual aim of this research into human development is to better understand birth defects which occur in 3% of pregnancies and are responsible for 20% of infant deaths. This includes conditions like spina bifida, hole-in-the-heart, and cleft lip and palate which often pose life-long medical problems for the child, caring challenges for the family, and a considerable financial burden for the health service. While pregnancy termination can be an option, the ultimate goal is to learn how birth defects develop in the embryo and fetus, so that preventive measures can be offered. These might involve vital nutrients like folic acid, or stem cell transplants which hold great promise for future disease treatment. Researchers are increasingly finding disruptions of genes that are associated with such diseases, raising the possibility that genetic counselling and perhaps gene therapy might be offered in future. All of these medical advances will be made more achievable by an improved understanding of how the human embryo and fetus develop.