Stem Cell Therapy 'Damage' Seen

Sadly another example where something appears to be safe in animals but has disastrous results in humans.

I wonder if the patient was informed that there was a risk of fatality. Because it seems to me, the proponents of research may tend to be optimistic about the level of risk. Anyone agreeing to be a research subject should be wary and make sure to be really well informed.

In Canada we have a totally bogus system for classifying risks of research. Any risk that's deemed equivalent to the patient's existing statistical medical risks can be classified as "minimal risk". That means, for example, if you're a male over 85 years of age (statistically dead) then fatal risks can be called "minimal risk". Or for example, if the research population is "tobacco smokers" then some fairly serious absolute risks could be imposed and referred to as "minimal risks". "Minimal risk" is the first criterion leading to approval of so-called "naturalistic" research involving waivers or alterations to informed consent - which should be entirely banned. And conveniently, when a risk has been classified as "minimal", the research is eligible for expedited review by a single member of an ethics board. (The boards are made up almost entirely of interested parties involved in research.)

Anyway, just wanted to hammer at the importance of informed consent. Back to Nuremberg, I say.

Sadly another example where something appears to be safe in animals but has disastrous results in humans.

That is why they reasearch is to lower the risks, it does not eliminate them.

Another way to look at it is in reearch on animals that have disastrous effect on the subject, may not happen on human subjects.

So in Canada, it pays to be healthy and not to smoke......or get old.

I feel we're only getting half the story here.

Yes. This is typical of most news publications. What is needed is for the majority of engineers/scientists to confront these limp-assed articles. Uneducated writers need to make a living, but not at the expense of the truth.

Fair enough that there could have been more detail in the story. I decided to spend an hour finding out about it - the sort of preliminary search I would do if I was considering it as an experimental treatment. As you say, get the facts first.

I should be very clear, my first remarks, and this summary of facts about the therapy, are in no way intended to condemn stem cell therapy in general or anything of the kind. But what I found in the literature does not support this treatment as a "stem cell therapy", and it doesn't point to poor practices on the part of the doctors (as in sloppy care), unless they used some additional treatments to promote the integration of the bone-derived stem cells into the kidney, which is not what you want to do on the basis of animal results. Of course, poor practices start in the library as well - the doctors should have read everything and done their homework before risking a patient's life. But doctors also rely on the researchers to be objective and candid with them when they come to recruit research subjects.

Like I said in the first place, optimism can interfere with objectivity, especially when desperation or serious need is involved. I found several optimistic reviews promoting the potential of the treatment in 2009.

http://www.ncbi.nlm.nih.gov/pubmed/19337150

http://www.ncbi.nlm.nih.gov/pubmed/20017833

http://www.ncbi.nlm.nih.gov/pubmed/19092639

All of these reviews acknowledge that the benefits of this therapy in animal experiments were due to paracrine (cell signalling) effects, not due to integration of the introduced stem cells.

Some studies reported successful integration of the cells, but the results could not afterwards be reproduced or verified. http://www.ncbi.nlm.nih.gov/pubmed/19838114

The majority of the studies report that paracrine effects - cell signalling which helped to stimulate the kidney's own self-regenerating cells and capabilities - were producing benefits, rather than introduced stem cells contributing to regeneration on a cellular basis. http://www.ncbi.nlm.nih.gov/pubmed/19955830

In fact, animal study results were equivocal about benefits where stem cell integration did occur. According to this review, also published December 2009, "...an improvement of renal function is observed without direct involvement in tubular epithelial engraftment. On the other hand, Bone Marrow cells have also shown not to improve renal function despite their tubular engraftment." http://www.ncbi.nlm.nih.gov/pubmed/19816390

In other words, benefits were obtained when the stem cells didn't take, but benefits were not obtained when the cells did take. It seems the success of the therapy depended on its failure.

If kidney function did not improve in animals with acute experimental injuries, it's reasonable to assume that these animals either died of their injuries when the graft succeeded, or were killed for the reading of their entrails very soon after. Was there enough information to conclude that the stem cell integration played no role in the fatalities?

Death by the (faulty) integration of the stem cells is what is described in this case. What is different from the animal results is that the cells clearly didn't do the "pleuripotent" thing to produce kidney cells. But the animal results suggest, even if they had become kidney cells, it would not be expected to benefit the patient.

On the basis of an hour reading the abstracts, I don't see that this therapy had passed the point where it should be green-lighted for testing in human subjects.

Next question: are there other, safer ways of inducing "paracrine effects" to promote regeneration of the kidney, without introducing the risk that stem cells will also integrate and negate the hoped-for benefits? Because this is where the research is pointing, not to (exogenous) stem cell therapy for the kidney.