Stem Cell Autopsy: The first teratoma case unfolded

by Alexey Bersenev on May 18, 2012 · 6 comments

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More than two years ago, in the first post of “Stem Cell Autopsy” series, I’ve linked to the 1996 Neurology report about the complication of intra-cerebral transplantation of fetal tissues. Recently, the story behind of this bizzare case, was described in the book “When Scientists Go Wrong” by Simon LeVay. You can read the ” neuroscience chapter” for free here. I was really thrilled by the story when was reading this chapter. There were a lot of interesting details. It turns out that It was the first and the only one case of teratoma development in cell tranplantation history. Today I’m sharing more details on this case and quotes from the book.

The author described a development of clinical fetal cell neurotransplantation and interviewed the key people, who was involved in the case of Parkinson’s Disease patient – Max Truex. Neurotransplantation of fetal brain tissue in Parkinson’s Disease was pioneered in 1987 in Sweden.

Then, in November 1988, the first American foetal transplant was performed by a team led by neuroscientist Curt Freed of the University of Colorado. Freed had researched the technique for years, first in rats (like the Swedes) and then in monkeys. This research was funded by federal grants, but when he began the human work Freed had to turn to private funds because the Reagan administration, concerned about the abortion issue, had banned the use of federal grants to support transplantations involving human foetal tissue.
For the first transplant, Freed selected a volunteer by the name of Don Nelson, a 51-year-old Denver man who had been suffering from Parkinson’s disease for 19 years. As with Max Truex, Nelson was deteriorating fast and he was desperate to try some new therapy. Freed obtained foetal tissue from an abortion clinic in the Denver area, dissected out the substantia nigra and (with the collaboration of a neurosurgeon) injected the foetal cells into the striatum on one side of Nelson’s brain.
If the Swedes were publicity-shy almost to the point of secretiveness, Freed was the very opposite: he held a news conference to announce the transplant just two days after the operation, long before he could know whether Nelson would experience any benefit from the procedure.

Years after diagnosis, Max was under observation of their family’s friend – neurosurgeon Paul Iacono (link). Dr. Iacono was brave enough to decide to take him in China and transplant fetal tissues into Max’s brain. It was 1989. The technique was pioneered in 1987. Very few physicians were able to perform this procedure around the world and all of them have rejected Max Truex. China was the only country which agreed to provide them a hospital bed and abundance of aborted fetuses.

In any event, Iacono said that he made great efforts to find a place where Truex could get a foetal transplant. ‘I tried all my friends all over the world – Sweden, Britain, Japan. I tried and tried. And eventually, after two or three years of following Max, I realised I had to do it myself.’

Another surprise had to do with money. According to Kay, the doctors, at the Zhengzhou hospital, or the hospital administrators, demanded a substantial fee – she thought it was in the range of $20,000 to $25,000 – to let the operation go ahead. Don said that Max told him the fee was close to the annual operating budget for the hospital.

Max’s parkinsonism symptoms improved after the transplant and he was fine during almost two years. But in March of 1991, he started to feel something strange and became concerned about his death.

Rebecca Folkerth is a pathologist who performed Truex’s brain autopsy. She was the only available neuropathologist on Sunday at New England Medical Center:

‘I answered my page on the Sunday night and I said, “OK, I’ll come and do this autopsy.” It sounded like Durso was having trouble getting anyone to help him.’

Folkerth reached the hospital around 9pm. ‘Once I got there, I got a call from Dr. Iacono,’ she says. ‘He told me the whole history and said, “Can I ask you to take some of the tissue fresh and freeze it?” I said, “OK, fine.”

Up to now, Folkerth hadn’t noticed anything unusual about Truex’s brain. ‘But as I was cutting it,’ she told me, ‘I made this observation, “Gee, look at this strange stuff in the ventricles, in the third and fourth ventricles, and in the lateral ventricles also.” I thought, “Isn’t that odd?” and I took a bunch of pictures. And I thought, “That looks like cartilage; isn’t that weird!” Even to the naked eye it looked like cartilage, and there were hairs – you could see them, just eyeballing it – the gross pictures are extremely dramatic.’

Brains don’t usually contain cartilage or hair, of course. Nor bone or skin, which she later discovered were also present. ‘You could see the hair shafts,’ she went on. ‘So I knew there was something very strange about this right away. Oh, this was the most strange thing I’d ever seen, and at this point it was the middle of the night. I was the only one there, looking at this case and thinking, “What the hell is this?” It was creepy. So here I am taking these pictures and thinking this is some mistake; this is a tumour – a teratoma.’

Lumps of glistening cartilage lined the floor of one of the ventricles. Part of one of the lateral ventricles was completely filled with a waxy, skin-like tissue. The fourth ventricle, which is located in the brainstem near nerve centres concerned with breathing and other vital functions, was packed full of hair and other tissues, so much so that some of the surrounding brain structures were compressed and discoloured.

There was no doubt that the teratoma originated from transplanted fetal brain tissue.

This whole experience left a big impression on Folkerth, and so over the next few months she devoted a lot of her free time to analysing the tissue samples from Truex’s brain. In the left and right striatum, where Iacono had deposited the tissue from the two 16-week-old foetuses, she found no surviving cells from the transplant, only scar tissue. This was consistent with findings from other research groups, who have reported that tissue from foetuses this old has a very low chance of surviving the transplantation procedure. Folkerth concluded that the reported improvement that Truex had experienced was not due to the presence of any transplanted nerve cells in his brain. Either just the damage caused by the injections had a beneficial effect, which didn’t seem terribly likely, or some other factor, such as the new drug that Truex received, was the reason.
What about all the weird tissues in the ventricles? These presumably arose from the tissue that Iacono had dissected from the very young, five- to six-week-old foetus and had injected into the left lateral ventricle. Folkerth believes that Iacono mistakenly included some tissue that was not from the embryo’s brain at all – tissue from just outside the brain that normally would have developed into the overlying bone, cartilage, skin, and hair.

Later on, Folkerth decided to proceed with publication, but without Iacono:

Iacono had been the initial driving force behind the autopsy, and it would have been natural for him to participate in publishing the findings that emerged from it. In fact, at a scientific meeting three months after Truex’s death, he announced that the results of the autopsy were ‘pending’. But later, Iacono seemed to lose interest in having the results published.

In the publication Folkerth did not mention American physician, who traveled in China with his patient. She also didn’t use a term “teratoma” to describe a cell mass from Max Truex’s brain. The story about publication is quite interesting:

After more than a year’s delay, they sent their manuscript to the New England Journal of Medicine, because that journal had already published several articles about foetal-cell transplantation for Parkinson’s disease. But the manuscript was rejected. ‘That was funny,’ says Folkerth. ‘I thought this was something that was definitely worthy of being in that particular journal.There seemed to be kind of a pro-transplant point of view in the other articles they had published.’
What Folkerth didn’t know was that her manuscript was reviewed by Curt Freed, a major enthusiast for foetal-cell transplantation and an author of one of those ‘pro-transplant’ articles in the NEJM.
The rejection of the manuscript caused another delay, but in 1995 Folkerth and Durso sent the manuscript to another, less prestigious journal,Neurology. It was accepted, and it appeared in 1996, five years after the autopsy it described.

Iacono didn’t respond to the Neurology article, or if he did his response didn’t get published. But the journal did publish a response from a research team that had begun to do foetal-cell transplants at the University of South Florida in 1993. Evidently, this team, like Curt Freed, was worried that Folkerth’s article would throw the field of foetal-cell transplantation into disrepute, and they expressed their feelings about what Iacono had done in unusually strong language. ‘This is a case of extremely poor tissue dissection,’ they wrote. ‘One wonders why this transplant was performed in China,’ they added, ‘outside of State and Federal regulations, Institutional Review Board oversight, and peer review scrutiny.’ ‘We should not be surprised,’ they concluded, ‘that poor science leads to poor outcomes.’

Finally, what Iacono thought about Truex’s death:

Iacono never abandoned his conviction that Truex was greatly helped by his transplants, and he rejected the idea that the tissue in his ventricular system caused his death. ‘There weren’t any signs of increased intracerebral pressure,’ he told me. ‘He wasn’t having urinary incontinence, he wasn’t showing signs of dementia, he wasn’t complaining of headaches. He was acting normally, and his wife said he came in and sat down and died. That just doesn’t sound like [ventricular blockage]. His death was officially signed out as a heart attack.’ (Kay says that Max’s death certificate lists only ‘Parkinson’s disease’ and does not mention any immediate cause for his death.)

So, we have confirmed case of teratoma development after fetal tissue transplantation in human brain. According the patients observation in clinical trials, this case is unique and only the one. Nevertheless, it’s well documented. I was really surprised by the fact that human embryonic tissues (5-6 weeks of gestation) still retain the pluripotency. What do you think?

Download 1996 Neurology report

PS: Special thanks to Doug Sipp for the link to the book chapter!

Related posts:

  1. Stem cell autopsy: clinical cases in lupus nephritis and multiple sclerosis
  2. Analysis of autopsy material after allogeneic mesencymal stromal cell infusions
  3. Stem cell autopsy: Two ALS cases of neurotransplantation in China

{ 6 comments… read them below or add one }

Jen Moody May 19, 2012 at 12:30 pm

I don’t think it necessarily means the cells retained pluripotency for that long. You could infer pluripotency if you knew the starting population was uniform. If the dissection was not precise, it could have included all kinds of multipotent progenitors.

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Alexey Bersenev May 19, 2012 at 2:00 pm

Jen,
I believe that it was only brain tissue. In the book, Folkerth discuss the possibility of graft contamination by surrounding tissues in case of inaccurate dissection. But she also can’t explain the presence of cartilage. So, it seem like the version of teratoma is more convincing for her.
I think the possibility to cross-contaminate brain tissue by multipotent progenitors from surrounding tissues is exist, but less likely.

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Jen Moody May 19, 2012 at 12:30 pm

btw, very interesting post:)

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Delree June 7, 2012 at 5:27 pm

The different gestational ages of the two cerebral tissues which were implanted in the patient brain ( 5 to 6 weeks gestational age i.e. embryonic tissue and 15 to 16 weeks gestational age i.e. fetal tissue) have to be stressed. It is most likely for us that the teratoma originates from the embryonic tissue graft rather than from the fetal one. Teratoma growth from embryonic tissue is indeed frequently described in the literature. This is not at all the case for fetal tissue implant. In our opinion, fetal graft may be rehabilitated.
Dr Paul Delrée and Dr. Very Coulic

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Amy Price June 10, 2012 at 7:58 pm

Could the needle draw going in have carried or introduced stray cells into the area which then were triggered to proliferate by the state of the foetal tissue? Inaccurate dissection makes no sense given the area and tissue they were working with?

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kodati vijayalakshmi June 13, 2012 at 6:37 am

all scientists and clinicians involved with stem cell research should read this case and be aware about the benefits and risks that may arise after stem cell transplantation.

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