Treating human diseases using adult cells taken from a patient and genetically reprogramming them so that they behave like embryonic stem cells has come a step closer.

In a paper published in Nature on October 13, scientists report the sequence of events for successfully correcting a gene mutation responsible for both cirrhotic liver disease and lung emphysema. They first took adult skin cells and corrected the gene mutation. Having done that, they next reprogrammed the adult cells to make them behave like induced pluripotent stem cells (iPSCs).

After completing the genetic correction in the cell line, the researchers introduced the iPSCs into a mouse. The mouse had a mutation that resembled the condition seen in humans.

That the successfully corrected gene was active in the liver cells was proved by the presence of normal alpha1-antitrypsin protein in both test tube and mouse experiments.

The iPSCs were able to function in the same way as their in vivo counterparts including glycogen storage, LDL-cholestrol uptake, albumin secretion etc. The authors also confirmed by two methods that the alphal-antitrypsin (A1AT) assay produced by the iPSCs cells in the liver showed complete absence of the mutant polymeric A1AT. Also, the iPSCs were engrafted into the animal model for liver injury without causing tumour formation.

“In addition, secreted A1AT showed an enzymatic inhibitory activity that was comparable to that obtained from normal adult [liver] cells,” the paper notes.

Earlier studies have shown that it was possible for correcting gene mutations of A1AT. Even correcting human iPS cell lines was also tried. But “this is the first demonstration, to our knowledge, of the generation of mutation-corrected patient-specific iPSCs, which could realise the therapeutic promise of human iPSCs,” the paper states.

The researchers selected a deficiency caused by a mutation in A1AT for this study. This gene is active in the liver where it is responsible for making a protein that protects against excessive inflammation. Any mutation results in inability to release the protein properly from the liver resulting in liver cirrhosis and lung emphysema.

Unlike harvesting embryonic stem cells that lead to the destruction of embryos, iPSCs use only adult cells and hence the question of embryo destruction does not arise.

Several studies have demonstrated that adult human cells reprogrammed to become induced pluripotent stem cells behave like embryonic stem cells. Hence, they are capable of becoming any of the 256 adult cells found in our body.