Weekly reads: teratoma in iPSC trial, Piero Anversa & friends, Athersys, China Initiative

It’s been mostly a downbeat week on the stem cell news front including a deep revisit by Reuters to the Piero Anversa case that has new revelations. It’s ugly stuff involving other folks too.

We’ll start on the iPS cell front, where a trial participant had a teratoma.

I’ve had a long-standing interest in the relationship between stem cells and tumors including teratomas.

Dr. Piero Anversa.

Links between stem cells, reprogramming, and cancer

Years ago in the earlier days of the iPS cell field, my lab published a paper on parallels between old-fashioned reprogramming methods and oncogenic transformation that generates cancer cells. Pluripotent cells such as iPS cells and ES cells have the ability to form teratomas in mice in lab experiments.

iPSC teratoma
Teratoma in patient who received a cell therapy made from iPS cells. “FIG. 1. Imaging features before treatment. (A) X-ray image. In the deltoid muscle of the left upper arm, a round, mixed- density mass with an unclear boundary of 9.6 · 5.2 cm was observed. The humeral cortex was intact. (B) Plain CT coronal scan showed a round, mixed-density mass in the deltoid muscle with an unclear boundary. (C) An enhanced CT axial scan showed uneven and moderate enhancement. (D) MRI T1W was dominated by iso-signals, with patchy high- and low-signal areas. (E) T2W also showed high-signal and patchy low-signal areas. The left axilla had multiple lymph node swelling. CT, computed tomography; MRI, magnetic resonance imaging.” Han, et al. Stem Cells & Dev.

When pluripotent stem cells are used to differentiate into a population of specialized cell type for transplant such as pancreatic cells, the hope is no stem cells are left.

IPSC trial generated a malignant teratoma

Now we have the report that is the first, to my knowledge, describing a clinical study participant who developed an immature teratoma after receiving differentiated cells made from their own iPS cells. It was a diabetes trial. From the paper it seems the tumor was a malignant teratocarcinoma-like tumor. This isn’t your everyday benign teratoma.

Here’s the paper: Distinctive Clinical and Pathologic Features of Immature Teratomas Arising from Induced Pluripotent Stem Cell-Derived Beta Cell Injection in a Diabetes Patient, Stem Cells & Dev. The authors conclude:

“Based on the data from few available clinical trials for iPSC-derived cell treatment of T2DM, its safety and validity need to be confirmed by more standardized clinical trials. More attention should be given to teratoma formation after iPSC-derived cell therapy for T2DM, which is more aggressive than typical teratomas.”

For context, several iPS cell studies are underway without reports of teratoma so it may be a rare occurrence.

In a way this paper could complicate life in the clinical and translational iPS cell arena but it also serves the purpose of raising awareness. Hopefully it’ll spark more rigorous differentiation and QC protocols across the board. I think most groups are being extremely careful.

Recommended reads including Piero Anversa piece

Here’s the Piero Anversa & friends investigation. Years after Brigham-Harvard scandal, U.S. pours millions into tainted stem-cell field, Reuters. This headline is way too general and could leave the wrong impression of the stem cell field being more generally problematic. It’s specifically the heart adult stem cell space that is the focus of the article and those who were in the orbit of Piero Anversa one way or another. Setting that aside for the moment, the Reuters piece raises some big concerns about grant and paper reviewing in that space. It also highlights how institutions and journals don’t always do an effective job of dealing with this kind of situation. Also, how is it that many in the adult stem cell/cardiac field continue to pretend nothing happened? And funders keep funding.

Stem cell clinic doctor Mark Berman died of COVID a few months back. Now we finally see a Dr. Mark Berman obituary.

The Brain Tumor Charity on a GBM trial, We respond to “promising” survival data from phase III trial of DCVax®-L. A concern here is that the unproven product is going to be sold privately to vulnerable patients.

Athersys future uncertain. I’ve covered Athersys quite a lot over the years here on The Niche. Some stem cell biotechs go through roller coaster rides and that’s been true for this firm over the past decade or so, but lately it’s been just about all downhill for Athersys. The firm had generally disappointing results in a stroke study. After that it laid off 70% of its workforce. The stock is down 75% YTD (ATHX). The MultiStem study didn’t meet its primary endpoint. Some investors remain hopeful.

Better news

To end on a high note, Haifan Lin is back as the Director of the Yale Stem Cell Program. Thank goodness. See the tweet below. There have been some very misguided investigations in a program started back during the Trump administration. See this piece from Science on how this “China Initiative” in America has evolved.

What stem cell or regenerative medicine stories caught your eye this week?

1 thought on “Weekly reads: teratoma in iPSC trial, Piero Anversa & friends, Athersys, China Initiative”

  1. Berman taking credit for pioneering SVF is a bit of a stretch. Plenty of people were doing it before he started. He was years late to that party. His innovation was creating a large treatment network in the US.

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