October 12, 2015–Regenerative medicine is a new and expanding area that aims to replace lost or damaged cells, tissues or organs in the human body through cellular transplantation. Embryonic stem cells (ESCs) are cells capable of long-term growth, self-renewal and can give rise to every cell, tissue and organ in the fetus’s body. Thus, ESCs hold great promise for cell therapy as a source of diverse differentiated cell-types. Two major bottlenecks to realizing such potential are allogenic (involving tissues or cells that are genetically dissimilar) immune rejection of ESC-derived cells by recipients and ethical issues.

Two Japanese scientists, Nobel laureate Shinya Yamanaka and Kazutoshi Takahashi, showed in 2006 that introduction of four genes in skin cells can reprogram fibroblasts into functional embryonic stem-like cells (also termed “induced pluripotent stem cells.”

Stem cell researchThe notion that as little as four genes are sufficient to reset the epigenome (a network of chemical compounds surrounding DNA that modify the genome without altering the DNA sequences) of a cell, opened a new avenue where scientists have attempted to convert different adult cells into other somatic cell types. Several subsets of cell types such as blood cells, nerve cells, heart cells and liver cells were converted from different adult cells by employing the direct conversion approach.

This discovery opened an attractive avenue that resolves both the ethical issue and the immune rejection problem of ESCs and the need for donor cells.

The placenta is the least understood human organ, but arguably one of the most important ones. It influences not only the health of a woman and her fetus during pregnancy, but also her lifelong health. Placental insufficiency occurs when the placenta does not develop properly, or is damaged.

Placental dysfunction diseases are associated with low birth weight, premature birth and birth defects. One such disease is fetal growth restriction that tends to display mild mental retardation and in severe cases causes fetal death. They also carry increased risk of complications for the mother. To date, tools to model or treat these diseases are limited because all attempts to isolate and propagate the human placenta precursor cells (i.e. trophoblast stem cells, cells that can form the placental cells) in the dish have failed.

Now, researchers from The Hebrew University of Jerusalem, led by Dr. Yosef Buganim of the School of Medicine-Developmental Biology and Cancer Research, have succeeded in converting skin cells into stable and fully functional induced trophoblast stem cells (iTSCs, the stem cells of the placenta that responsible for the formation of most cells in the placenta).  These skin-derived TSCs look like native TSCs, and function and contribute to developing placenta.

The success of this study will grant a real chance for women who suffer from placental dysfunction diseases to have healthy babies. It is important to note that these cells do not hold any risk since they integrate only into the placenta and not to the embryo itself.

 

Full Citation:

“Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells”

Cell Stem Cell, September 24, 2015.

Benchetrit H1, Herman S1, van Wietmarschen N2, Wu T3, Makedonski K1, Maoz N1, Yom Tov N1, Stave D1, Lasry R1, Zayat V1, Xiao A3, Lansdorp PM4, Sebban S1, Buganim Y5.

 1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.

 2European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, AV Groningen 9713, the Netherlands.

 3Yale Stem Cell Center and Department of Genetics, Yale University, New Haven, CT 06520, USA.

 4European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, AV Groningen 9713, the Netherlands; Skolkovo Institute of Science and Technology (Skoltech), Novaya str. 100, Skolkovo Moscow Region 143025, Russia.

5Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.