Abstract
BackgroundHuman 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.MethodsA 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.ResultsWe 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.ConclusionsThe 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.
Highlights
Human embryonic stem cells hold tremendous promise for cell replacement therapies for a range of degenerative diseases
We performed a screen for Good Manufacturing Practice (GMP)-compatible culture media suitable for the derivation of Human embryonic stem cell (hESC) with human dermal fibroblast (hDF) as feeders
The clinical-grade hESC lines described here, are of the highest quality yet produced for clinical therapeutic use, for the following reasons: (i) they have been derived from sperm and eggs procured and embryos generated in an in vitro fertilisation (IVF) laboratory designed and operated
Summary
Human embryonic stem cells (hESCs) hold tremendous promise for cell replacement therapies for a range of degenerative diseases. We aimed to derive new clinical grade hESC lines of highest quality from fresh surplus GMP grade human embryos. Human embryonic stem cells (hESCs) hold enormous promise as tools for understanding normal human development and diseases and for new drug discovery. There are specific requirements for hESC lines intended for clinical use Such hESCs should be derived under stringent ethical guidelines, from traceable and tested donors, in a GMP-grade culture and quality management system. GMP [4] is defined by both the European Medicines Agency and the US Food and Drug Administration, in order to meet a number of pre-set specifications with regard to the development, manufacturing, and quality control of medicinal products aimed for clinical use.
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