Somatic Cell Reprogramming

According to Jacob Hanna from the Jacob Hanna Lab, reprogramming of adult somatic cells into pluripotent stem cells may provide an attractive source of stem cells for regenerative medicine. It has emerged as an invaluable method for generating patient-specific stem cells of any cell lineage without the use of embryonic stem cells.

A revolutionary study in 2006 showed that it is possible to convert adult somatic cells directly into pluripotent stem cells by using a limited number of pluripotent transcription factors and is called as iPS cells. Currently, both genomic integrating viral and nonintegrating nonviral methods are used to generate iPS cells. However, the viral-based technology poses increased risk of safety, and more studies are now focused on nonviral-based technology to obtain autologous stem cells for clinical therapy. In this review, the pros and cons of the present iPS cell technology and the future direction for the successful translation of this technology into the clinic are discussed.

Mere months after Kyoto University researchers announced in 2007 that they had discovered how to turn skin cells into induced pluripotent stem cells (iPS cells), Jacob Hanna used these new types of cells to cure mice of sickle-cell anemia, in which a genetic defect causes bone marrow to make defective red blood cells. Hanna, a fellow at the Whitehead Institute, took skin cells from a diseased mouse and reprogrammed them create iPS cells, which behave like embryonic stem cells, readily turning into any cell type in the body. He then corrected the sickle-cell genetic defect and prodded the iPS cells to develop into the type of marrow stem cell that manufactures a mouse’s blood cells. These healthy cells were transplanted back into the mouse, whose immune system accepted them as the animal’s own tissue. The treated mouse began producing healthy red blood cells on its own.

Hanna’s work was a turning point for iPS research, says George Daley, director of the Stem Cell Transplantation Program at Boston’s Children’s Hospital and a professor at Harvard Medical School: “It was a beautiful demonstration of a mouse model of a human disease, and really demonstrated the potential of iPS cells.”

Before iPS cells can be used to treat diseases such as sickle-cell anemia in humans, a lot of work has to be done to make sure they won’t cause adverse side effects and to improve the efficiency of deriving them from skin cells. Hanna is now developing simulations to understand what happens when cells are reprogrammed, and he’s searching for new types of human stem cells that could be easier to turn into adult cells.–Nidhi Subbaraman

Genetically modified pigs for biomedical applications have been mainly generated using the somatic cell nuclear transfer technique; however, this approach requires complex micromanipulation techniques and sometimes increases the risks of both prenatal and postnatal death by faulty epigenetic reprogramming of a donor somatic cell nucleus. As a result, the production of genetically modified pigs has not been widely applied.

We provide a simple method for CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing in pigs that involves the introduction of Cas9 protein and single-guide RNA into in vitro fertilized zygotes by electroporation. The use of gene editing by electroporation of Cas9 protein (GEEP) resulted in highly efficient targeted gene disruption and was validated by the efficient production of Myostatin mutant pigs. Because GEEP does not require the complex methods associated with micromanipulation for somatic reprogramming, it has the potential for facilitating the genetic modification of pigs.