Expert opinions on the first model of early human embryos from skin cells

Biotech News: In a discovery that may revolutionise research into the causes of early miscarriage, infertility and the study of early human development – an international team of scientists led by Monash University has generated a model of a human embryo from skin cells. 

The team, led by Professor Jose Polo, has successfully reprogrammed these fibroblasts or skin cells into a 3-Dcellular structure that is morphologically and molecularly similar to human blastocysts (a stage that the human embryo reaches approximately five to six days after fertilisation). Called iBlastoids, these can be used to model the biology of early human embryos in the laboratory as published in Nature.

Professor Martin Pera, Chair of Stem Cell Sciences at The University of Melbourne, Florey Neuroscience and Mental Health Institute and the Walter and Eliza Hall Institute of Medical Research said “Two studies published in Nature today show for the first time that human pluripotent stem cells can give rise to three-dimensional structures that closely mimic the properties of the embryo just around the time it implants into the womb. Jose Polo’s team from Monash University and their collaborators started with stem cells made by reprogramming of adult skin cells, while Jun Wu’s group at the University of Texas Southwestern Medical Centre began with human embryonic stem cells.

“Both groups created conditions in a petri dish that directed the starting stem cell populations to form the three cell types found in the embryo before implantation: the precursors of the embryo itself, and two types of essential supporting cells that provide for transfer of nutrients to the embryo.

“The structures resembled human embryos in their overall appearance and in their molecular makeup. Both groups showed that these embryo models, called iBlastoids after the embryonic blastocyst stage they resemble most closely, could continue to develop in vitro in a fashion that mimicked the further growth and differentiation of the embryo after implantation into the womb.

“These model systems have great potential for providing insight into early human development, and for enabling the discovery of new medical approaches to establishing and maintaining a healthy pregnancy.

“While the blastoids described by both groups are excellent models, they do differ in some respects from normal embryos.

“The studies were performed under strict ethical oversight, but they will undoubtedly prompt further discussion regarding what work should be permitted with embryo models in a dish, particularly as they become more refined and capture later stages of human development.

“To help inform these discussions, the International Society for Stem Cell Research has considered these questions carefully, and will soon be issuing guidelines for the conduct of embryo model research,” he noted.

A/Professor Kuldip Sidhu, co-founder and director, CK Cell Technologies and Conjoint with University of New South Wales Medicine, said “Since 1978 with the birth of the first test-tube baby, more than 8 million babies have been born with assisted reproduction to-date. In Australia, about one in twenty is born using this technique. The success rate varies but is consistently high, above 35% worldwide, which is more than with natural cycles in women.

“Assisted reproduction also brings in concern about inherent birth defects and ailments in the babies associated with this procedure. So it’s very timely that these two papers in Nature explicitly describe a procedure to generate iblastoids from pluripotent stem cells that resemble natural blastocysts and claim that the same can be utilised to study early human development and the ailments associated thereof.

“Although the efficiency of the procedure remains low, nevertheless it represents a novel in vitro model for early human development. Authors of both these papers could generate two types of stem cells, epiblast and trophectoderm cells, by using ‘whole iblastoids culture’ but it will be pertinent to demonstrate that epiblast from these iblastoids can be dissected out and the relevant naïve epiblast stem cells are generated to validate close homology with blastocysts.

“These studies set a solid ground to optimise this system further as a tool to assess the early human development and more including the ailments that are associated with assisted reproduction,” he concluded.