Cells Weekly – August 2, 2015

by Alexey Bersenev on August 2, 2015 · 0 comments

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Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!

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1. Update from the first iPS cell-based clinical trial
As you may know, the first iPS cell-based clinical trial in Japan has been suspended – read here and here. Over the last few days, more details about trial suspension came to the light. This week, New Scientist – one of the first from “western media”, publicized this news:

Analysis of the patient’s cells revealed six mutations. Three were genes that had been deleted and three were changes to nucleotides, including one in an “oncogene” linked with a low risk of cancer. The mutations were not detectable in the original skin cells from the patient, suggesting that they probably occurred as a result of the iPS-cell procedure. “Either they were there at undetectable levels in the skin cells, or they were caused by the iPS cell induction process,” says Shinya Yamanaka of Kyoto University in Japan…

However, the title of New Scientist article is too crude. Trial’s investigator Masayo Takahashi went public and commented on Knoepfler’s blog:

… but the main reason for the suspension was the regulatory change.
The mutated genes were not driver genes for tumor formation and the finding of the mutation was not something that called for a halt of the trial according to the protocol. We are planning to move to allogeneic transplantation…

and more on New Scientist piece:

The New Scientst’s article omit the part of my comment “but the main reason for the suspension was the regulatory change. The mutated genes were not driver genes for tumor formation and the finding of the mutation was not something that called for a halt of the trial according to the protocol.”
And the title of it “Cancer scare halts pioneering stem-cell trial to cure blindness” is completely wrong. I am afraid it will cause the public’s fear for stem cell treatment.

and on “regulatory change”:

I will explain about the regulatory change after the report from ministry of education will come out. It will be within a month.

She also was engaged in few conversations on twitter today – see here and here.

Paul Knoepfler summarized this discussion in his blog post today:

This development also raises a 2nd question as to whether there will be a domino effect now of other clinical studies or trials that are in the works using IPSC switching to allogeneic paths as well. In other words, is this a historic, turning point moment for the IPSC field in Japan overall away from an autologous path?

As always with a great comment by Jeanne Loring:
It’s not possible to know that “the 2nd patient’s IPSC reportedly had six mutations that were not present in the original somatic cells”. Think about it: each iPSC clone comes from one somatic cell. Unless you did whole genome sequencing on that exact somatic cell, by itself (which you can’t do, because it’s the source of the iPSC clone), there is no way to know if the variants originated in the somatic cell or were acquired during expansion of the iPSC clone.

Social media took a lead! I think, it’s great that she is openly sharing with us all details of this trial. I’ll continue to follow this discussion and will update you.

2. Update on “stem cell lawsuit” – Piero Anversa against Harvard
It was dismissed! Retraction Watch reported this week:

The defendants — who included Gretchen Brodnicki, the dean for faculty and research integrity, and Elizabeth Nabel, president of Brigham and Women’s Hospital — had asked for all of the claims to be dismissal. In a document dated July 27, district court judge Denise J. Casper agreed, noting:

the Court will dismiss a pleading that fails to plead “enough facts to state a claim to relief that is plausible on its face.”

The document details some background on Anversa and Leri’s allegations, for example that an inquiry panel convened to look into allegations of misconduct failed to do so within the deadline…

3. Robust expansion of kidney cells in culture
A group of researchers published a protocol for expansion of nephron progenitor cells (NPC), derived from ES cells. They were able to expand these cell as much as one billion-fold!

FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated.

4. Organoids boom
Nature posted this week a nice overview of organoids technology:

The current crop of organoids isn’t perfect. Some lack key cell types; others imitate only the earliest stages of organ development or vary from batch to batch. So researchers are toiling to refine their organoids — to make them more complex, more mature and more reproducible. Still, biologists have been amazed at how little encouragement cells need to self-assemble into elaborate structures. “It doesn’t require any super-sophisticated bioengineering,” says Knoblich. “We just let the cells do what they want to do, and they make a brain.”

Highly recommended to read!

5. US government investment in regenerative medicine
US Government Accountability Office (GAO) released a report, where provided a data for investment in the field of regenerative medicine since 2012:

Seven federal agencies invested—that is, conducted or funded—approximately $2.89 billion in regenerative medicine research in fiscal years 2012 through 2014. Most (88 percent) was invested by the National Institutes of Health.

6. Interview with bioethicist Nita Farahany on human germline modification
Paul Knoepfler posted an interview with bioethicist Nita Farahany. She has a very strong “pro-” position in human germline modification debate:

PK: You’ve been characterized in various debates, to put it simply, as being on the side arguing the “pro-designer baby” case. Is that correct? And why?

NF: No. I’m in favor of mitochondrial transfer, but not nuclear gene editing at this time. We haven’t reached a point in the technology where nuclear gene editing could be done with an expectation of safety and efficacy. Still, the bright line between somatic and germline modification – it’s not tenable. Could I be convinced on nuclear modification in the future if there’s more information? Possibly. I’m not opposed to germline modification ever happening.

Highly recommended!

7. New Methods and Protocols:
Direct conversion of human fibroblasts to induced serotonergic neurons (Mol Psych)
Generation of prostate organoids from human ES cells (PLoS ONE)
ES cell-derived myocardial precursors in model of myocardial infarction (PLoS ONE)

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