Cells Weekly – August 24, 2014

by Alexey Bersenev on August 24, 2014 · 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!

A couple of announcements:
* I’ve gotten few requests for access to public dataset “Stem cell therapeutic products on the market“. Apparently, the link didn’t allow to view it by anyone. Now the link should work – find it here. Please let me know if you still have problems with access. Table was recently updated.

* On September 11 CIRM is organizing free webinar “Use of iPS Cells as Screening Tools and Therapeutics“. There will be 3 great speakers (including Keith Wonnacott from FDA). I’d highly recommend you to take this opportunity and attend a webinar!

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1. Use of direct cell reprogramming for whole organ engineering in vivo
Researchers from University of Edinburgh, for the first time, were able to re-create whole thymus in mice, based on fibroblasts, directly reprogrammed into thymic epithelium by single factor. The single magic factor – FOXN1 is critical for development of thymic epithelium. This study is an extension of previous work by Clare Blackburn’s group.

iTECs thus demonstrate that cellular reprogramming approaches can be used to generate an entire organ, and open the possibility of widespread use of thymus transplantation to boost immune function in patients.

2. Use of Ixmyelocel-T in dilated cardiomyopathy – results of clinical trial
US-based company Aastrom published results of Phase 2a studies, assessing safety and efficacy of their cellular product Ixmyelocel-T in patients with dilated cardiomyopathy. The publication mixes results of two trials – IMPACT-DCM and Catheter-DCM. The results are mixed, because some efficacy end points were not met and major adverse cardiovascular events (MACE) were not reduced in non-ischemic dilated cardiomyopathy:

Intramyocardial injection with ixmyelocel-T reduces MACE and improves symptoms in patients with ischemic DCM but not non-ischemic DCM.

The studies were underpowered (number of patients and design) to assess efficacy fully. The company is currently recruiting up to 108 patients to Phase 2b study.

3. Humanized pig hearts survive up to one year in primates
Results of very important xenotransplantation study were recently published. Researchers assessed 4 different gene modifications in order to alter pig hearts immunologically. These hearts were transplanted into baboons under immunosuppression. The longest graft survival time was one year:

Genetically engineered pig hearts (GTKOhTg.hCD46.hTBM) with modified targeted immunosuppression (anti-CD40 monoclonal antibody) achieved long-term cardiac xenograft survival. This potentially paves the way for clinical xenotransplantation if similar survival can be reproduced in an orthotopic transplantation model.

4. Xenotransplantation assay to test cancer stem cells
Sara Nolte nicely summarized on the Signals blog the assay for testing cancer initiating cells

What is a CSC researcher trying to accomplish by using this technique? By examining tumour growth of a particular sample in mice, researchers can ultimately observe what is called the “tumour-initiating capacity” of that sample, or in other words, whether or not those transplanted cells can form new tumours.

Highly recommended for any junior cancer researcher!

Also read from our archive: Cancer stem cell assays and controversies – Interview with Mark Shackleton

5. Moving toward the first “brain rejuvenation” trial
Do you remember recent buzz about “brain rejuvenation” studies? Guess what – it’s moving to clinical trial! New Scientist reports:

So the billion-dollar question is: would a GDF11 boost have the same effect in humans? Wyss-Coray thinks it will, having taken the next step of injecting young human blood plasma into old mice.
Now, the final step – giving young human blood plasma to older people with a medical condition – is about to begin. Getting approval to perform the experiment in humans has been relatively simple, says Wyss-Coray, thanks to the long safety record of blood transfusions…
So in early October, a team at Stanford School of Medicine will give a transfusion of blood plasma donated by people under 30 to older volunteers with mild to moderate Alzheimer’s.

Will “young plasma” boost Alzheimer’s brain? What is your bet?

6. Safety control of stem cell-derived tumors in vivo
Prof-of-concept study, which demonstrates the control of stem cell-associated tumorigenesis, was published in Stem Cells journal. The authors sorted Oct4+ and Oct4- bone marrow cells, genetically modified them in order to track/ control and transplanted them into the mouse/ rat brains. They used suicide gene-based “safety switch” to eradicate tracked cells:

Engraftment of mouse and rat Oct4 positive BM-derived hypoblast like stem cells (m/rOct4+ BM-HypoSC’s) resulted in yolk-sac tumor formation in the healthy brain which were monitored longitudinally using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI).

Both cell lines were eradicated efficiently in vivo by ganciclovir (GCV) administration indicating successful suicide gene expression in vivo, as assessed by MRI, BLI and histology.

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