SENS5 Conference on Aging and Regenerative Therapies was Fantastic

And here’s why. I wrote some notes about the talks I found interesting. The ones that I haven’t listed were also very exsiting.

1. Bio-electrospraying is a novel method of forming an engineered organ

Dr. Suwan Jayasinghe from the University College London shared the successful work of his scientific group in electrospraying cells to form viable structures. The common methods of creating biological scaffolds with living cells are ink jet printing and electrospraing. Dr. Jayasinghe explained that bio-electrospraying is a quite promising new methods, not only because it doesn’t damage the cells, but also becuase it allows to manipulate with cell drops of smaller diameter than the regular ink jet printing. This technique can be used to produce seeded scaffolds for artificial organ creation and trating damaged or diseases organs, like for example, the heart.

2. Liver regeneration

Dr. Shay Soker from the Wake Forest Institute for Regenerative Medicine pointed out the necessity of creation of artificial organs. Aging, trauma and immune strikes cause severe health problems. We can treat them with organ transplantation, but it’s a zero-sum game. The demand on new organs is huge and growing, but the number of donor organs is tiny. There’s an option – bionic limbs, for instance, but masines wear out too. The better solution is to grow organs from the patient’s own cells.

Organs consist of cells and scaffolds. Scaffolds must:

1. Support 3D structure

2. Mimic the microenvironment

decellularization provides good scaffolds that retain the archtecture of the organ with its blood vessels including the tiny capillaries. Dr. Soker tolld the audience about the seccess in regenerating the miniature liver. They took livers from rats, ferrets and pigs, decellularized them and analyzed the obtained scaffolds. The vasculature was intact. The extracellular matrix proteins, such as collagen 1, 3, 4, laminin and fibronectin, were present. Seeding with cells was done through central and portal veins. Interestingly, seeded scaffolds have anti coagulating features. Researchers were also excited to see that cells can find their own niches. Endothelial cells go to vessels and hepatic cells go to parenchyma. The engineered livers were functional. Urea and albumin were secreted. This is an important step towards human liver regeneration.

3. Lung engineering

Dr. Laura Niklasson from Yale University is working on lung engineering. Human lung is an extremely complicated organ. There’s 23 generations of branching of airways, they are up to 200 microns in diameter. 70 square meters for gas exchange. More than 100 million air sacks all together. Engineered lung must have right mechanical properties, autologous cells, adequate surface area for gas exchange and adequate barrier to prevent flooding of airways with blood constituents after implantation.

Researchers used donor lung scaffolds. They took rat lungs, decellularized them and repopulated with pulmonary cells. The cells were semigeneic, that means they were almost genetically identical rat cells. The lung was cultured in a bioreactor. Besearchers were breating the lung during culturing. They used perfusion system of culture. They seeded pulmonary epithelium and vascukar endothelium cells. When Dr. Niklasson examined the integrity of blood vessels, it was ok. But some of elastin was stil present. And that’s bad so far. Also some of the air sacks got infused with staining, so the result is not perfect just yet. It seems like there are local instructions in the matrix that tell the cells where to land. Endothelial cells form a very dense population in vessels.

Scientists implanted engineered half lung in a rat. It was 95% as efficient as a native lung in terms of gas exchange. But in several hours they got trombosis. Also they saw a little bit of blood cells in airways, so the barrier was not perfect. After being improved this technique can be used to engineering human lungs.

4. Generation of functional thymus ex vivo

John Jackson gave a beautiful overview of thymic involution and told us about the ongoing experiments in the Wake Forest Institute for Regenerative Medicine on thymus engineering.

 

5. Zscan4 gene may provide immortality to stem cells

Dr. Minoru Ko is studying immortality of stem cells in the National Institute on Aging. Embryonic stem cells are remarkable, because they are pluripotent, they have self renewal, immortality and genome stability. Immortality is the ability to defy cellular senescence and undergo more than 250 doublings without undergoing crisis or transformation.

Researchers used embryogenomics and systems biology approach to identify differential gene expression in preimplantation embryos and other kinds of cells. They ruled out that the most interesting gene is Zscan4. It is expressed in 5% of the cells in the embryo, it can be turned on and off, but it’s crucial for proliferative potential. Knock down of Zscan4 leads to ES culture crisis by day 8. They have massive karyotype problems, but this can be alleviated. Telomere shortening is one of the mechanisms for karyotype deterioration in Zscan4-knockdown embryonic stem cells. When they turned off telomerase and overexpressed Zscan4, they still could see telomere elongation.

It was telomerase independent telomere elongation.

This gene is colocalized with meiosis-specific homologous recombination proteins on telomeres. Zscan4 may be the master gene that provides immortality among other things in embryonic stem cells. That’s the hypothesis. Researchers can accelerate Zscan4 cycle. Maybe it’s active at first and the cell is an embryonic stem cell, but over time its expression deminishes. But then at some point of time Zscan4 kicks in again and restores things back to normal. Maybe if we can accelerate Zscan4 cycles we could increase proliferative potential of stem cells. Zscan4 expressed constantly blocks proliferation of cells. You need to have it oscilating to keep cells proliferating.

6. Non-aging regeneration system in the brain

I personally found the talk by Dr. Charles Greer the most fascinating one. Aparently, there is a subsytem in our brain that is constantly regenerating. The rate and quality of this regeneration process doesn’t decline with age. It’s the oldfactory system. Sensory neurons in olfactory system die every 6-8 weeks. Neurogenesis is constant. New neurons come from the subventricular zone. It’s like a river of migrating neurons to olfactory bulb. The number of newly formed neurons a day is amazing – 10,000.

Vascular organization is the framework of migration. If we turn off VEGF with siRNA then there will be no migration. There are no changes in size of glomeruli with aging. Cell number, cell dencity doesn’t go down with aging too. The question is why is this system so special? What factors play the role in maintaining such an exeptional regenerative capacity thoughout life?