Manufacturing Human Embryoids in Petri Dishes

Category Biotechnology

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Using human stem cells, scientists have created lab-grown embryo-like structures inside petri dishes that form major 'layers' of tissues defining the early stages of human development. The Hanna lab have now extended the timeline of lab-gestation to at least 14 days post-implantation, which could help couples struggling to conceive. Their research has advanced two techniques: reverted stem cells to a completely naïve state, and an electronically-controlled device that bathes the embryoids in waves of nutrients simulating the conditions in the womb.

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Forget sperm meets egg.

Using human stem cells, scientists have created human embryo-like structures inside petri dishes. These lab-grown blobs develop multiple structures that mimic a human embryo after implantation into the uterus—a major milestone for fertility—and last at least 14 days.

A decade ago, manufacturing embryo-like structures, or embryoids, without reproductive cells would have seemed ludicrous. But as scientists increasingly map out the convoluted molecular journey towards human conception, it’s becoming possible to do away with sperm and egg in order to peek into the "black box" of early human development.

The Hanna lab have embarked on a roadmap to culture human embryos from stem cells to a 10 day post-implantation stage in the lab, which is further than any other research group has achieved.

It still sounds like a Frankenstein experiment. But the endeavor isn’t macabre scientific curiosity. Very little is known about the first few weeks of human pregnancy, when development most often tends to go awry. Studying models mimicking these early stages—without the controversy of biological samples—could help couples struggling to conceive and shine a light on the mysteries of lost early pregnancies.

The development of human embryoids in petri dishes has made it possible to study pre-implantation development without samples from real human embryos.

A new study published in Nature from embryoid veteran Dr. Jacob Hanna now pushes the lab-gestation timeline forward. The team turned human embryonic stem cells into embryoids that model early human embryos. Like their biological counterparts, the lab-based blobs developed major "layers" of tissues defining the early stages of human development.

"The drama is in the first month, the remaining eight months of pregnancy are mainly lots of growth," said Hanna. "But that first month is still largely a black box. Our stem-cell-derived human embryo model offers an ethical and accessible way of peering into this box." .

The Hanna lab have optimised an electronic device and a suite of chemical reagents that provide the right physiological conditions for embryogenic human stem cells

Recipe for an Embryoid .

Two years ago, the same team released a blockbuster result: egg meets sperm isn’t necessary to spark life, at least in mice. Using mouse stem cells, the team discovered a chemical soup that could nudge the cells into embryo-like structures inside a petri dish.

"The embryo is the best organ-making machine and the best 3D bioprinter—we tried to emulate what it does," said Hanna at the time.

Unlike the mouse embryoids cultured in 2017, Hanna's team have succeeded in culturing human embryoids that express canonical markers of embryonic development relevant to early human embryos post-implantation in the uterine wall

The idea seems relatively simple: all embryonic cells have the potential to become any other cell type. But these cells are also highly social. Depending on their environment—for example, which chemical or hormonal signals they receive—they self-organize into tissues.

Culturing embryoids relies on two advances, both from the Hanna lab.

One places reverted stem cells into a completely naïve state—a tabula rasa that wipes away any identity. We often think of stem cells as a uniform crowd, but they’re actually on a spectrum of development. Each step forward guides the cell’s development towards a specific cell type or organ. However, a naïve stem cell has the potential to grow into any body part.

The embryos survived for 14 days outside the womb, making them the longest lasting ever known to be cultured in vitro without the help of a uterus

Completely rebooting to naïve stem cells makes it easier to integrate stem cells into their hosts—regardless of whether it’s in humans or mice.

Another advance is an electronically controlled device that bathes the embryoids in waves of nutrients. Like a pacemaker, the pump simulates how nutrients wash over embryos in the womb, all the while controlling oxygen levels and atmosperic pressures.

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