Using induced pluripotent stem cells to reverse sickle cell anemia in mice

by on December 16, 2007 · 3 comments

in Journal club, model

Blogging on Peer-Reviewed Research Scientists have recently made a breakthrough that uses human skin cells to produce stem cells, obviating an ethical problem of using embryos. A group of scientist led by Rudolf Jaenisch at MIT now reports the use of this type of cells – so-called “Induced Pluripotent Stem (iPS)” cells – to treat sickle cell anemia in mice.

After extracting fibroblast cells from tails of transgenic mice that carry a mutant form of gene associated with sickle cell anemia, they were overexpressed with four transcription factor genes known to convert them into iPS cells. Then, they were able to replace a mutant gene with the correct one by the homologous recombination technique. After the gene correction, the iPS cells were transduced to become hematopoietic progenitor cells. Irradiation followed by transplantation of these cells in the sickle cell anemic mice led to reversal of a number of phenotypes associated with this disease.


Experimental scheme for in vitro reprogramming of skin fibroblasts with defined transcription factors combined with gene and cell therapy to correct sickle cell anemia in mice (Hanna et al., Science Express 2007; DOI: 10.1126/science.1152092)

This proof-of-concept study highlights that we are getting one step closer to using iPS cells generated from a patient for the treatment of various genetic disorders. However, an immediate problem with this approach is a possibility of insertional mutagenesis in cancer-causing genes during viral transduction to introduce transcription factor genes to induce stem cells. In addition, one of the four transcription factor genes – c-myc – is associated with cancer, although a recent report shows that scientists were still able to obtain iPS with omission of this gene and this approach reduced tumorigenicity . Therefore, with further safety studies, clinical trial of iPS treatment may be conducted soon in five years.

Science published online Dec 6, 2007; DOI:10.1126/science.1152092

{ 3 comments… read them below or add one }

Alex January 22, 2008 at 7:58 pm

Jae-Won, thank you for news.
One step closer but still so far from reality, because – you’re right – safety issues.
I quote here opinion one of leading scientist in somatic cell nuclear transfer – Miodrag Stojkovic – about safety and iPS:
“The recent generation of induced pluripotent stem (iPS) cells has put the feasibility of SCNT in regenerative medicine under intense scrutiny. Along with many other scientists, we applaud the former achievement. However, at this early stage of development, we do not consider iPS cells as a substitute for SCNT. As has been stated by other scientists, the use of genes and retroviruses known to cause cancer in mammals and retroviruses known to have the ability to disrupt the normal DNA function and stimulate the birth of cancer cells [4, 5] makes questionable any possible application of iPS in regenerative medicine, especially cell therapy. Although some proponents of reprogramming argue that these problems are purely technical and easily surmountable, currently it is vital to maintain the pace of research on more controversial fronts, such as the use of human oocytes in SCNT.”

so what do you think about perspectives of iPS? Will stick on the bench or go to bedside?


Jae-Won January 24, 2008 at 6:02 pm

Hi Alexey, thanks for your comment. To me, whether a certain technology will remain on the bench or evolve into the bedside really depends on whether scientists only talk about potential pitfalls of a given technology/scientific and do not do anything about it (which is quite common), or they are actually willing to solve potential pitfalls using their strengths: the ability to solve problems scientifically.

Having said that, if we are able to find a rule behind genomic integration of a given retro/lenti viral vector, a possibility of a given gene integrated near oncogenic promoters could be controlled. Dr. Fredick Bushman is working on this type of work at Penn. I think a revolution in this area will provide an opportunity for iPS to become therapeutics.

What is your thought?



Alex January 27, 2008 at 10:29 pm

to Jae-Won –
I’m more pessimistic about future of iPS,
so my answer is NO so far,
i feel like it’s gonna be translated “from bench to the other bench”.
We will see.


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