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. CD34+ cells for myocardial infarction patients – results of clinical trial
Press release of company NeoStem about preliminary results of Phase 2 cardiac cell therapy study, triggered lively discussions among professionals. I summarized the reasons for such discussions here. The investors “punished” NeoStem in the next day of news release (stock dropped -30%), because company did not provide explanation for changing primary endpoints on trial record. 4 days later, Neostem posted new clarifying press release, where provided explanation for changing study’s endpoints. However, it remains unclear why company did not share this information with investors in July (when endpoints were changed), but rather did it on the night of news release.
2. Stem cell origin of fibrosis
Harvard’s Humphreys lab described new kind of perivascular stem cells, which is a major contributor to organ fibrosis after injury. There cells have characteristics of mesenchymal stromal cells and express Gli-1 marker:
Genetic lineage tracing analysis demonstrates that tissue-resident, but not circulating, Gli1+ cells proliferate after kidney, lung, liver, or heart injury to generate myofibroblasts. Genetic ablation of these cells substantially ameliorates kidney and heart fibrosis and preserves ejection fraction in a model of induced heart failure.
So, stem cell are involved in many pathological processes and could be sometimes “bad guys”. Interesting part of work is therapeutic targeting of Gli1+ cells to stop/ prevent organ fibrosis. You can read more on potential commercialization here.
3. Commercial release of bioprinted product for drug testing
US-based company Organovo finally (it was long-awaited!) announced commercial release of liver tissue bioprinted product exVive3D:
Organovo’s exVive3D Liver Models are bioprinted, living 3D human liver tissues consisting of primary human hepatocytes, stellate, and endothelial cell types, which are found in native human liver. The exVive3D Liver Models are created using Organovo’s proprietary 3D bioprinting technology that builds functional living tissues containing precise and reproducible architecture. The tissues are functional and stable for at least 42 days, which enables assessment of drug effects over study durations that well beyond those offered by industry-standard 2D liver cell culture systems.
Well, good luck Organovo and let’s competition begin!
4. Future perspectives of somatic cell nuclear transfer – interview with Dieter Egli
This week, Paul Knoepfler interviewed Dieter Egli – a man behind the recent study about comparability of iPS and SCNT-derived stem cells. I find this interview very informative and productive. It touches many controversial topics. One excerpt:
PK: What are your thoughts at this point as to the future of NT-ESC? Do you think they will have clinical relevance down the road as the basis for stem cell therapies or is that less likely now? In addition to possible translation to the clinic, is there more we can learn from NT-ESC and this kind of reprogramming?
DE: It is neither more nor less likely. There is no therapeutic application of reprogrammed stem cell lines yet. There are so many uncertainties that depend on biological, economical, and logistical factors, and on the patenting landscape, that it is hard to predict the outcome. With these many uncertainties, it would be risky to put all eggs into just one basket. I think the nuclear transfer field is going to have a strong presence and will remain a primary research focus of my lab.
Also read some discussion on recent controversy in comment.
5. Long-term persistence of in vivo reprogrammed cells
Very interesting study was published this week in Nature Biotechnology. Extending and building upon of famous Melton’s direct reprogramming 2008 study, the authors tested long-term persistence of in vivo reprogrammed beta cells and their therapeutic value. Excerpt from Harvard Gazette:
“The efficiency of reprogramming has always been an issue,” Zhou said. “Until now, the new cells have either dropped dramatically in number or disappeared completely,” he said, noting that since his work with Melton in 2008 there have been reports published in other programing systems that question whether the reprogrammed cells could be stable enough ultimately to be useful.
“What we have demonstrated is that yes, the reprogrammed cells can be useful, and for that to happen you have to create a niche environment in which the cells can survive,” Zhou continued. “We have improved the reprogramming efficiency to a point where one can create a large enough number of the new cells that the new cells create their own niche environment.”
6. Identification of “youth factors” to boost aged brain
We’ve written about parabiosis model for stem cell and aging research. Recent study from Stanford’s Wyss-Coray lab made a big buzz. This week, Shelly Fan reported from Society for Neuroscience meeting about extension of this work:
The key is to setup a robust system that screens for strong candidate youth factors with few mistakes. Scientists harvested the blood from three different models: normal mice aging, human aging and the mice parabiosis model. The idea is to use a technique called protein microarray, which assesses changes in the levels of thousands of proteins at the same time, and to look for overlapping candidate factors across all three models. By looking for factors that decrease with age, the researchers would be able to narrow the candidates down to a tenable amount for further research. After finding these potential “hits”, researchers can then directly deliver each candidate protein to aged mice and see if the treatment improves learning and memory.
7. How aging affects mesenchymal stem cells
Another group of researchers from Stanford U, demonstrated that pro-vascular/ angiogenic qualities of mesenchymal stromal cells (MSC) could be especially affected with age:
We identify an age-related depletion of a subpopulation of MSCs characterized by a pro-vascular transcriptional profile. Supporting this finding, we demonstrate that aged MSCs are also significantly compromised in their ability to support vascular network formation in vitro and in vivo. Finally, aged MSCs are unable to rescue age-associated impairments in cutaneous wound healing.
The results of this study could have direct implications to autologous MSC-based therapy.
8. Lessons from Dendreon’s failure
Dendreon – the first US company with approved immunocellular product on the market – filed recently for bankruptcy. Mark Curtis wrote a nice summary of some lessons we can learn from Dendreon’s failure. Highly recommended!
The cost density of PROVENGE would not have been such a dilemma for Dendreon if physicians’ claims were being processed in a timely manner. Due to the novelty of the product, payers were slow to the mark and doctors, apparently, grew tired of waiting for reimbursement.
Many, if not all, cell-based immunotherapies will have similar issues given their high cost and the nature of their administration to patients. So, efficient frameworks for the reimbursement of advanced cellular products will be required in the future if we are to expect physicians to prescribe these treatments.