Cells Weekly – September 5, 2016

by Alexey Bersenev on September 5, 2016 · 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!

1. Amniotic Therapies versus FDA
US-based manufacturer of amniotic tissue-derived products for regenerative medicine Amniotic Therapies has received warning letter from FDA. This letter is warning company for many reasons, but two major are the following: (1) misbranding and marketing their product as 361 HCT/P, which they are drugs and must be regulated as 351 drugs and (2) contamination of one lot with mycoplasma and 4 adverse events as a consequence. The letter was issued on August 17 and it gives only 15 days for response. Apparently, company response was not satisfactory and FDA may order to cease operation (I was not able to find documented proof of it). The company responded by lawsuit against FDA (“to block FDA’s order”) – you can read details here. Few hours after filing lawsuit, Texas federal judge barred FDA from “shuttering” of company “over perceived sanitary problems”. The company said that contamination was doctor’s fault, who administered the product to patient without reading package insert.

2. Update on Macchiarini’s investigation
Karolinska University Hospital, which investigated ethical research misconduct by tissue engineering pioneer Paolo Macchiarini, has released report this week. Hospital, basically admitted that Macchiarini’s hire should not even happen in the first place:

“Much went wrong in connection with Macchiarini’s transplants of synthetic trachea,” said Asplund in a statement when he presented the results of the inquiry on Wednesday.
“Macchiarini should not even have been employed at the hospital. There were shortcomings in how the decisions about the transplants were made and how they acted on existing laws. The hospital has a big task ahead to ensure patient safety and trust.”

Some leadership positions were suspended. Read more details on For Better Science blog:

The Asplund report found gross violations of medical ethics, patient right, even recruitment processes when analysing the history of the scandal around the Italian surgeon. Unlike repeatedly declared by both KI and KS, Macchiarini’s trachea transplants were not medical emergencies and not compassionate care cases…

Also read some details from Nature News:

The affair has damaged trust in clinical research in Sweden, says the report, but the hospital is already taking steps to improve things. For example, it has prepared internal guidelines for experimental clinical methods and for how to deal with whistle-blowers.
Acting KI vice-chancellor Karin Dahlman-Wright said in a statement that “it would be extremely regrettable if the Karolinska Institutet had exerted any kind of pressure” in hiring Macchiarini. The KI will publish its own report on the case on 5 September. Macchiarini and his lawyer declined to comment on the latest report.

3. Credit for discovery of medical optogenetics
Anna Vlasists by STAT News wrote a great piece about development of medical optogenetics field and its pioneers. The major theme of her article is who should be credited for key discoveries and pioneering the field. We all know that Karl Deisseroth and Ed Boyden are widely credited as pioneers, but another researcher – Zhuo-Hua Pan, conducted key experiments first. Pan just got “less lucky” with his publication (it stuck in reviews for 2 years), so, Deisseroth and Boyden published first:

So Pan and Dizhoor wrote a paper about their work and submitted it to Nature on November 25, 2004, according to the submission letter Pan shared with STAT. The editors at Nature suggested they send it on to a more specialized journal called Nature Neuroscience, which rejected it. Early the next year, Pan sent the paper to the Journal of Neuroscience, where it was reviewed but then again rejected.

Why didn’t Pan’s paper get published first? He may never know the answer. After Boyden’s paper came out, Pan wrote to the editor at Nature Neuroscience asking how they could have rejected his paper but published Boyden’s.
In her response, the editor replied that while the papers were similar, Boyden et al. presented theirs as a new technology rather than as a scientific finding. Pan’s paper, it seemed, was too narrow, only focusing on using channelrhodopsin to restore vision, while Boyden’s paper took the broad view of thinking of channelrhodopsin as a tool for neuroscience in general.

Anna Vlasists discusses the problem with delaying of publications and crediting scientists for discoveries. We can draws parallels with CRISPR patents/ crediting war, since both technologies have a “Nobel Prize potential”.

As for the invention itself, some scientists say Pan may not have had the big, award-worthy vision that Deisseroth and Boyden had. Stefan Herlitze, one of the others who was scooped for the first publication about channelrhodopsin in neurons, said, “Of course I have to say, Deisseroth and Boyden, they really developed the field further.”
Boyden echoed this. “Karl and I were very interested in the general question of how to control cell types in the brain,” he said. “In recent years, we worked to push these molecules to their logical limits.”
So maybe it doesn’t matter who invented optogenetics, just who has stretched science’s boundaries the furthest.
Asked whether he deserves the recognition that Boyden and Deisseroth have enjoyed, Pan declined to answer. He later told STAT that Deisseroth “also did a very excellent job, no doubt. But he’s also very lucky because if our paper was ahead of him, the story would be different. We would have gotten more credit.”

Highly recommended to read!

4. Role of hematopoietic stem cells in steady state hematopoiesis
It is remain not very clear if all blood cell types are developed from one hematopoietic stem cell (HSC) in normal hematopoiesis, because of limitations of conventional transplantation models. In these models, host bone marrow severely damaged by lethal irradiation and donor cells can skew hematopoietic repopulation in toxic marrow environment. Recent studies, challenged significant contribution of HSCs in immune reconstitution. Results of very recent study, which used more appropriate model of steady state hematopoiesis, were published in Immunity.

Inducible genetic labeling showed that transgene-expressing HSCs gave rise to other phenotypic HSCs, confirming their top position in the differentiation hierarchy. The labeled HSCs rapidly contributed to committed progenitors of all lineages and to mature myeloid cells and lymphocytes, but not to B-1a cells or tissue macrophages.

5. Accelerated aging of immune system after hematopoietic stem cell transplantation
Researchers demonstrated that hematopoietic stem cell transplantation in patients with hematological malignancies significantly accelerates aging of immune system. They measured aging marker p16 on blood cells before and after of chemotherapy with hematopoietic stem cell transplantation. Turns out that expression of this aging marker on T-cells was significantly higher after transplant. Effect was especially profound in autologous transplant and in patient with more cycles of chemotherapy. The senior author said:

“Many oncologists would not be surprised by the finding that stem cell transplant accelerates aspects of aging,” said the study’s senior author Norman Sharpless, MD, director of UNC Lineberger and the Wellcome Distinguished Professor in Cancer Research. “We know that years after a curative transplant, stem cell transplant survivors are at increased risk for blood problems that can occur with aging, such as reduced immunity, increased risk for bone marrow failure, and increased risk of blood cancers. What is important about this work, however, is that it allows us to quantify the effect of stem cell transplant on molecular age.”

6. Cancer stem cell database
Overview of new public database for identification of characterization of cancer stem cell is described this week in Stem Cells TM.

Herein, we describe the Cancer Stem Cells Therapeutic Target Database (CSCTT), the first online database to provide a rich bioinformatics resource for the display, search, and analysis of structure, function, and related annotation for therapeutic targets of cancer stem cells. CSCTT contains 135 proteins that are potential targets of CSCs, with validated experimental evidence manually curated from existing literatures.

Link to database.


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