Researchers from the Whitehead Institute for Biomedical Research in Cambridge, Mass. and Kyoto University in Japan used an innovative new method to reprogram adult cells to an “embryonic-stem-cell-like” state, and successfully cured mice with sickle-cell anemia:
This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed “induced pluripotent stem” (IPS) cells, which recently have been derived in mice as well as humans.
The research, reported in Science Express online on December 6, was carried out in the laboratory of Whitehead Member Rudolf Jaenisch…
The mouse model had been designed to include relevant human genes involved in blood production, including the defective version of that gene.
To create the IPS cells, the scientists started with cells from the skin of the diseased mice, explains lead author Jacob Hanna, a postdoctoral researcher in the Jaenisch lab. These cells were modified by a standard lab technique employing retroviruses customized to insert genes into the cell’s DNA. The inserted genes were Oct4, Sox2, Lif4 and c-Myc, known to act together as master regulators to keep cells in an embryonic-stem-cell-like state. IPS cells were selected based on their morphology and then verified to express gene markers specific to embryonic stem cells. To decrease or eliminate possible cancer in the treated mice, the c-Myc gene was removed by genetic manipulation from the IPS cells.
Next, the researchers followed a well-established protocol for differentiating embryonic stem cells into precursors of bone marrow adult stem cells, which can be transplanted into mice to generate normal blood cells. The scientists created such precursor cells from the IPS cells, replaced the defective blood-production gene in the precursor cells with a normal gene, and injected the resulting cells back into the diseased mice.
The blood of treated mice was tested with standard analyses employed for human patients. The analyses showed that the disease was corrected, with measurements of blood and kidney functions similar to those of normal mice.
“This demonstrates that IPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells,” says Jaenisch.