A sustainable model for human germ cell precursors

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Human Primordial Germ Cells (PGCs) are the earliest precursors to egg cells (oocytes) and sperm which are needed to keep humanity alive and reproduce. Medical researchers are trying to study their function and development using models of these cells called primordial human germ cells (PGCLC).

Human PGCLCs have been developed at several research centers, including the lab led by Toshi Shioda, MD, PhD, at the Center for Cancer Research at Massachusetts General Hospital (MGH) and at Harvard Medical School.

Natural PGCs exist only in embryos. The models were created to overcome ethical and technical barriers surrounding the use of human embryonic tissue in experiments.

“My primary interest is using PGCLCs for toxicology research to understand how exposure to chemicals or prescription drugs might affect human reproduction,” Shioda said.

He and his colleagues are using the cells to study in the lab how exposing women to chemicals such as general anesthesia could introduce heritable changes that can then be passed on to future generations without creating DNA mutations. This process is known as epigenetic inheritance.

They are also using this model to study how PGCs become testicular cancer, the most common malignancy in boys and young men.

The catch is that hPGCLCs do not survive long in the laboratory and quickly lose their germ cell-like characteristics unless they are carefully and thoroughly cured with the use of blood serum or added chemicals. And even when these special cells survive and grow in lab dishes, they tend to stray from their germ cell type identity and become other cell types.

But as Shioda and his colleagues explain in the journal Stem Cell Reportsthey developed a method to maintain hPGCLCs and their germ cell-like functions in cell culture without requiring special handling, with the cells surviving and continuing to replicate for at least five months without losing their primordial germ cell-like characteristics.

Using these cells, they have successfully generated hPGCLC carrying various genetic mutations linked to testicular cancer and are working to create the first synthetic tumor model of human testicular cancer with defined genetic mutations to aid in the cancer prevention and treatment research.

The work was supported by donations from the RICBAC Foundation and the Escher Fund for Autism as well as grants from the National Institutes of Health.

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Material provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

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