Stem cells are special. Present in abundant quantities during fetal development — and in smaller but still significant numbers in some adult organs — these undifferentiated cells have not yet been told whether to turn into muscle, bone, blood, or nerve. This is what makes them so significant for medical research. Stem cells have the potential to turn into many of the human body’s cell types. As such, they offer a promising resource for doctors to treat patients who need organ and tissue transplants. They also offer a way to study the effects of disease on human cells that aren’t in a human’s body. Stem cells have even shown potential for treating cancer.
Some types of human cells have proven difficult to grow from stem cells, though, especially gray matter (neurons) and white matter (oligodendrocytes) because scientists have trouble inducing the genetic changes in them that are necessary to make the cells differentiate. This is especially significant since nerve cells are some of the body’s cells that are least likely to regrow in the event of damage.
But in a study published Thursday in the journal Stem Cell Reports, scientists report that they’ve developed a way to grow millions of nerve and muscle cells from human embryonic stem cells way more quickly and reliably than was previously possible.
To do this, the researchers used a platform that they call “optimized inducible overexpression” — OPTi-OX for short. This platform allows scientists to optimize gene targeting, which makes the forced gene expression in stem cells more reliable and more controllable.
The researchers used OPTi-OX to induce stem cells to develop into neurons, white matter brain cells, and skeletal muscle cells. They say they can use it to induce growth of any cell type, though, which could open doors for new therapies.
“The efficiency and speed of the presented forward programming system will enable high-throughput drug screens and toxicology testing, in vitro modeling of hereditary leukodystrophies, and the development of cell-transplantation strategies,” write the study’s authors.
This study employs embryonic stem cells, which have come under fire for years since they come from the tissue of fetuses. Though usually the products of in vitro fertilization, they carry a strong association with abortion. And while this stem cell research is the product of cells that might have one day grown into humans, the OPTi-OX technique could be used to help doctors understand human disease and treat patients more effectively.
Summary: The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes.
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