Scientists have developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue without the use of embryonic cells. The research makes great strides in addressing a major practical challenge in the development of stem cell based medicine.
The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called “induced pluripotent stem cells” or “iPS cells”).
The hope of most researchers in the stem cell field is that one day it will be possible to use stem cells, which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells, to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson’s disease, as well as from injuries. The creation of induced pluripotent stem cells from adult cells sidesteps ethical concerns associated with the use of embryonic stem cells, and allows the generation of stem cells matched to a patient’s own immune system, avoiding the problem of tissue rejection.
The creation of human induced pluripotent stem cells was first reported in December 2007, and while the work was a major breakthrough, it was unsafe and inefficient with a success rate of roughly one in 10,000 cells. The safety issue was addressed in May 2009 and this current study makes major strides in solving the efficiency problem.
The researchers found two chemicals, ALK5 inhibitor SB43142 and MEK inhibitor PD0325901, used in combination were highly effective in promoting the transformation of fibroblasts into stem cells. The two-chemical technique boosted the efficiency of the classic genetic method by 100 times.
Attempting to increase the efficiency of the process even further, the team decided to enlist another natural pathway, the cell survival pathway. After screening a library of compounds targeting this pathway, the team focused on a novel compound called Thiazovivin.
The researchers found that a technique using Thiazovivin in combination with the two previously selected chemicals, SB43142 and PD0325901, beat the efficiency of the classic method by 200 times.
References:
1. Tongxiang Lin, Rajesh Ambasudhan, Xu Yuan, Wenlin Li, Simon Hilcove, Ramzey Abujarour, Xiangyi Lin, Heung Sik Hahm, Ergeng Hao, Alberto Hayek, et al. A chemical platform for improved induction of human iPSCs. Nature Methods. doi:10.1038/nmeth.1393.
