New Stem Cell Finding Bodes Well for Future

Medical Use in Humans

A major concern over using stem cells is the risk of tumors: but now a new study shows that It takes a
lot of effort to get induced pluripotent stem (iPS) cells to grow into tumors after they have been
transplanted into a monkey !he findings will bolster the prospects of one day using such cells
clinically in humans
"aking iPS cells from an animal#s own skin cells and then transplanting them back into the creature
also does not trigger an inflammatory response as long as the cells have first been coa$ed to
differentiate towards a more speciali%ed cell type &oth observations' published in Cell Reports today'
bode well for potential cell therapies
(It#s important because the field is very controversial right now') says Ashleigh &oyd' a stem*cell
researcher at +niversity ,ollege -ondon' who was not involved in the work (It is showing that the
weight of evidence is pointing towards the fact that the cells won#t be rejected)
Pluripotent stem cells can be differentiated into many different speciali%ed cell types in culture . and
so are touted for their potential as therapies to replace tissue lost in diseases such as Parkinson/s and
some forms of diabetes and blindness iPS cells' which are made by reprogramming adult cells' have an
e$tra advantage because transplants made from them could be genetically matched to the recipient
0esearchers all over the world are pursuing therapies based on iPS cells' and a group in 1apan began
enrolling patients for a human study last year &ut work in mice has suggested controversially that even
genetically matched iPS cells can trigger an immune response' and pluripotent stem cells can also form
slow*growing tumors' another safety concern
Closer to human
,ynthia 2unbar' a stem*cell biologist at the 3ational Institutes of 4ealth in &ethesda' "aryland' who
led the new study' decided to evaluate both concerns in healthy rhesus maca5ues 4uman stem cells are
normally only studied for their ability to form tumors in mice . as a test of pluripotency . if the
animals/ immune systems are compromised' she says
(6e really wanted to set up a model that was closer to human It was somewhat reassuring that in a
normal monkey with a normal immune system you had to give a whole lot of immature cells to get any
kind of tumour to grow' and they were very slow growing)
2unbar and her team made iPS cells from skin and white blood cells from two rhesus maca5ues' and
transplanted the iPS cells back into the monkeys that provided them It took 78 times as many iPS cells
to form a tumor in a monkey' compared with the numbers needed in an immunocompromised mouse
Such information will be valuable for assessing safety risks of potential therapies' 2unbar says And
although the iPS cells did trigger a mild immune response . attracting white blood cells and causing
local inflammation . iPS cells that had first been differentiated to a more mature state did not
Robust sites
Although this was the first study to look at undifferentiated iPS cells transplanted back into the monkey
they came from' it is not the first primate study to monitor how cells differentiated from iPS cells fare
when transplanted Scientists at 9yoto +niversity in 1apan found that monkey iPS cells that had been
differentiated into dopaminergic neurons (the type of neuron that dies in Parkinson/s disease) and
transplanted into the brain survived for months without forming tumors 0esearchers at 0I9:3 in
9obe' 1apan' got similar results when transplanting iPS cells first coa$ed into forming retinal pigment
epithelial cells' cells that support the photoreceptors at the back of the eye 3either study observed
tumors forming' and both found that transplants are not rejected when animals receive their own cells
4owever' both of the sites involved normally have a fairly weak capacity to trigger immune responses
2unbar' by contrast' differentiated iPS cells into bone precursor cells and placed them into small
scaffolds just under the skin' a location with a robust immune response !he transplants did not cause
irritation or inflammation' probably because the differentiated cells do not e$press embryonic proteins
absent in mature tissues &y eight weeks' new bone had formed Almost a year later no tumors had
formed' and bone formation persisted
"ore work is needed because evidence from other studies suggests that the bone precursor cells
themselves may damp down the immune system' says 2unbar She is hoping to repeat these studies
using iPS cells that have been coa$ed into making heart and liver cells