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. Vitamin increases mice lifespan via stem cells modulation mechanism
International group of researchers have published very interesting study this week, where demonstrated that nicotinamide adenine dinucleotide (NAD) “revitalize” senescent muscle stem cell via modulation of their mitochondrial activity. Aged mice, treated with NAD precursor nicotinamide riboside, had “rejuvenated” not only muscle stem cells, but also neural stem cells and melanocytes. Overall, such treatment led to increased mouse lifespan. The study’s author said:
“We gave nicotinamide riboside to 2-year-old mice, which is an advanced age for them,” said the researcher. “This substance, which is close to vitamin B3, is a precursor of NAD+, a molecule that plays a key role in mitochondrial activity. And our results are extremely promising: muscular regeneration is much better in mice that received NR, and they lived longer than the mice that didn’t get it.”
2. Fully chemical reprogramming
Forget about transcription factors, all you need now to get any specialized cell type from fibroblasts are few small molecules. Researchers led by Sheng Ding from Gladstone Institutes published 2 studies this week to prove the principal of fully chemical direct reprogramming. First study, published in Cell Stem Cell, showed direct reprogramming of mouse fibroblasts into neural stem cells by cocktail of 9 small molecules. The second study, published in Science, demonstrated direct reprogramming of human fibroblasts into cardiomyocytes by 9 small molecules. Paul Knoepfer covered these studies on his blog.
3. Precise chemical control of engrafted cells
New methodology of function control of engrafted cells was described by researchers from University of Wisconsin-Madison on a model of Parkinson’s disease:
Here, we show tunable rescue of motor function in a mouse model of PD, following transplantation of human midbrain dopaminergic (mDA) neurons differentiated from hPSCs engineered to express DREADDs (designer receptors exclusively activated by designer drug). Administering clozapine-N-oxide (CNO) enabled precise DREADD-dependent stimulation or inhibition of engrafted neurons, revealing D1 receptor-dependent regulation of host neuronal circuitry by engrafted cells.
Very cool approach! It could be widely applicable in cell therapy.
4. More on stem cell hype in regenerative medicine
Leonid Schneider continues to blog about recent Macchiarini’s scandal and unethical conduct of medical research in regenerative medicine. In his recent post he discussed faith in bone marrow and criticized funding of European projects, which include using bone marrow for tissue engineering
All considered, bone marrow cells do not seem to be doing much when seeded on trachea scaffold, even when locked up in a bioreactor and sternly instructed to regenerate tracheal tissue by qualified elite clinical scientists at UCL or Karolinska. When they find themselves inside this doctor-duped patient’s airway, the bone marrow cells most likely just die.
5. Long-term outcome in gene therapy of SCID-ADA
As you may know GSK is about to get the first European approval for gene therapy of one inherited form of immunodeficiency – SCID-ADA. They transferred technology from Italian San Raffaele Scientific Institute. This week, a group of authors from San Raffaele and GSK published a report on long-term outcome and quality of life after experimental gene therapy in 18 patients with SCID-ADA. The results are great! GSK is planning to get approval soon, based on these data.
Overall survival was 100% over 2.3 to 13.4 years (median: 6.9 years). Gene-modified cells were stably present in multiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n=17, Patient 1 data not available). Immune reconstitution was demonstrated by normalization of T cell subsets (CD3+, CD4+, and CD8+), evidence of thymopoiesis, and sustained T cell proliferative capacity. B cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination.
6. Perfusion culture bioreactors in cell manufacturing
The Cell Culture Dish blog posted a summary of perfusion cell culture in biomanufacturing.
In perfusion there are different ways to keep the cells in culture while removing spent media. One way is to keep the cells in the bioreactor by using capillary fibers or membranes, which the cells bind to. Another does not bind the cells, but rather relies on filtration systems that keep the cells in the bioreactor while allowing the media to be removed. Another method is the use of a centrifuge to separate cells and return them to the bioreactor.
7. New methods and protocols:
A novel lineage restricted, pericyte-like cell line isolated from human ES cells (Sci Rep)
Failure of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in rats (PLoS ONE)
Labeling of mesenchymal stem cells for MRI with single-cell sensitivity (Int J Nanomedicine)