October 4, 2022

Human primordial germ-cell-like cell (PGCLC) preservation for reproductive health research

Human primordial germ cells (PGCs) are the earliest progenitors of eggs (oocytes) and sperm, which are required to keep humanity alive and reproducing. Human primordial germ-cell-like cells are models of these cells used by medical researchers to examine their function and development (PGCLCs). The specification and progression of germ cells to gametes is a one-of-a-kind process with significant biological and therapeutic significance. Primordial germ cells (PGCs) are the germline’s starting cells in mammals, and they emerge during early embryogenesis. The research on PGCs in model species is limited due to the low number of these cells inside the developing embryo.

The capacity to create germ cells from pluripotent stem cells (PSCs) is beneficial in human regenerative medicine and animal breeding. Germ cell-like cells (GCLCs) have been isolated from mouse and human pluripotent stem cells (PSCs), but not from pig PSCs, which are thought to be an excellent model for stem cell applications. The germ cell lineage, which is the source of totipotency, can differentiate into any form of cell. Errors in germ cell derivation and differentiation result in infertility, malignancies, and even congenital abnormalities in kids. As a result, generating germ cells from PSCs has the potential to be useful in the research of germ cell growth processes and infertility therapies. PGCLC induction from mouse and human PSCs has made significant progress. It has been observed that mouse and human PSCs may be directly induced to become PGCLCs, spermatogonia, and even mature gametes.

Human PGCLCs were created in a number of research facilities, including the laboratory of Toshi Shioda, MD, Ph.D., at the Center for Cancer Research at Massachusetts General Hospital (MGH) and Harvard Medical School. Natural PGCs can only be found in embryos. The models were developed to evade the ethical and technological challenges associated with the use of human foetal tissues in investigations. Their primary focus is on the use of PGCLCs in toxicological studies to better understand how chemical or prescription medication exposure may influence human reproduction.

The scientists are utilising lab cells to investigate how exposure of women to drugs such as general anaesthesia might produce heritable alterations that can subsequently be passed on to future generations without causing DNA mutations. This is referred to as epigenetic inheritance. This model is also being used to explore how PGCs develop into testicular cancer, the most frequent malignancy in boys and young men. The problem is that hPGCLCs do not survive in the laboratory for long and rapidly lose their germ-cell-like characteristics unless they are properly and painstakingly fostered with the use of blood serum or additional chemicals. Even when these particular cells survive and thrive in laboratory dishes, they tend to lose their germ-cell identity and transform into other types of cells.

However, Shioda and colleagues have developed a method for maintaining hPGCLCs and their germ-cell-like functions in cell culture without the need for special handling, with the cells surviving and continuing to replicate for at least five months without losing their primordial germ-cell-like features, as described in the journal Stem Cell Reports. They have successfully grown hPGCLCs that carry numerous genetic abnormalities associated with testicular cancer using these cells and are trying to construct the first synthetic tumour model of human testicular cancer with specific genetic alterations to help in cancer prevention and therapy studies.

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