Ye Jinpei, Bates Nicola, Soteriou Despina, Grady Lisa, Edmond Clare, Ross Alex, Kerby Alan, Lewis Philip A, Adeniyi Tope, Wright Ronnie, Poulton Kay V, Lowe Marcus, Kimber Susan J, Brison Daniel R
Division of Cell Matrix Biology and Regenerative Medicine, School of Biology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, 46 Grafton Street, Manchester, M13 9NT, UK.
North West Embryonic Stem Cell Centre, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Oxford Road, Manchester, M13 9WL, UK.
Stem Cell Res Ther. 2017 Jun 5;8(1):128. doi: 10.1186/s13287-017-0561-y.
Human embryonic stem cells (hESCs) hold tremendous promise for cell replacement therapies for a range of degenerative diseases. In order to provide cost-effective treatments affordable by public health systems, HLA-matched allogeneic tissue banks of the highest quality clinical-grade hESCs will be required. However only a small number of existing hESC lines are suitable for clinical use; they are limited by moral and ethical concerns and none of them apply Good Manufacturing Practice (GMP) standards to the earliest and critical stages of gamete and embryo procurement. We thus aimed to derive new clinical grade hESC lines of highest quality from fresh surplus GMP grade human embryos.
A comprehensive screen was performed for suitable combinations of culture media with supporting feeder cells or feeder-free matrix, at different stages, to support expansion of the inner cell mass and to establish new hESC lines.
We developed a novel two-step and sequential media system of clinical-grade hESC derivation and successfully generated seven new hESC lines of widely varying HLA type, carefully screened for genetic health, from human embryos donated under the highest ethical and moral standards under an integrated GMP system which extends from hESC banking all the way back to gamete and embryo procurement.
The present study, for the first time, reports the successful derivation of highest-quality clinical-grade hESC lines from fresh poor-quality surplus human embryos generated in a GMP-grade IVF laboratory. The availability of hESC lines of this status represents an important step towards more widespread application of regenerative medicine therapies.
人类胚胎干细胞（hESCs）在一系列退行性疾病的细胞替代疗法中具有巨大潜力。为了提供公共卫生系统能够负担得起的具有成本效益的治疗方法，将需要高质量临床级hESCs的HLA匹配异体组织库。然而，现有的hESC系中只有少数适合临床使用；它们受到道德和伦理问题的限制，而且没有一个在配子和胚胎采集的最早和关键阶段采用良好生产规范（GMP）标准。因此，我们旨在从新鲜的多余GMP级人类胚胎中获得新的最高质量的临床级hESC系。
对不同阶段的培养基与支持饲养层细胞或无饲养层基质的合适组合进行全面筛选，以支持内细胞团的扩增并建立新的hESC系。
我们开发了一种新型的两步连续培养基系统用于临床级hESC的衍生，并成功地从在综合GMP系统下按照最高伦理和道德标准捐赠的人类胚胎中生成了7个具有广泛不同HLA类型的新hESC系，这些系经过仔细的基因健康筛选，该系统从hESC库一直延伸到配子和胚胎采集。
本研究首次报告了从GMP级体外受精实验室产生的新鲜低质量多余人类胚胎中成功衍生出最高质量的临床级hESC系。这种状态的hESC系的可用性代表了再生医学疗法更广泛应用的重要一步。
