Stem Cells Make Significant Progress Over The Past Week

Discoveries include a new carrier scaffold, skin to blood stem cell transition, more efficient generation of brain stem cells, and a precursor protein.

Assistant professor Alireza Dolatshahi-Pirouz and colleagues have created a new bio-material scaffold for the transportation and transplantation of stem cells in the body. Bio-material scaffolds are a growing topic of interest in the stem cell community because of their ability to insulate stem cells from damage, as well as attract endogenous stem cells to the target location.

The concept is similar in essence to stem cell derived exosome therapy except for instead of extracting vesicles from the body and re-injecting them containing stem cells, a semi-synthetic scaffold composed of hydrogel is constructed to contain and attract them.

Typically speaking, exogenous growth and differentiation factors that would otherwise accompany stem cell transplantation can be both toxic to the body and expensive.

However, scientists have discovered how to shield stem cells on their way to an injury site by using semi-organic “shells” composed of hydrogel, which help to control any complications by reducing the amount of irrelevant contact, and therefor reducing the amount of exogenous factors required to counterbalance any loss caused by friction with other tissue.

In an attempt to narrow down and fine-tune the science of bio-material scaffolds scientists tested 63 different nano-engineered hydrogels, selecting the best performing bio-material that can both protects the stem cell from damage while facilitating it’s spontaneous differentiation. Back in September it was proven that skeletal stem cells could heal bones and cartilage, and this team was particularly concerned with regeneration of bone, however as you will see later on – the same hydrogel was used to heal heart tissue.

“Bone is a dynamic tissue that is continually being built, broken down and rebuilt in a process called remodeling. This process is controlled by many interacting factors, and once this balance is disturbed, the problem arises. When we get older such an imbalance is often caused by hormonal changes, and is intensified by our cells becoming less effective and fewer in numbers. The idea behind this novel system is to bring a semi-synthetic scaffold into the body that attracts stem cells and provides the requirements to turn them into bone cells, and thereby, bring the balance back to the bone remodeling cycle.”

Originally the team chose hyaluronic acid, a carbohydrate found all around the body that has already been proven useful in tissue engineering. Unfortunately cross-linked hyaluronic acid based hydrogel scaffolds still possess some weaknesses, including poor load bearing quality, and shock absorption.

So, to create a stronger, more durable material, the team fused hyaluronic acid with another compound called alginate from seaweed. Then, for a final touch, they reinforced the whole composite scaffold with clay nanomaterials. This led to sufficient durability while still remaining porous enough to enable transport of nutrients within the hydrogel.

Alginate has only proven more useful as times goes on. Back in november, alginate was combined with graphene to create a shape-shifting material that transforms in response to the surrounding environment.

After the team transplanted stem cell filled hydrogels over-top of a model bone defect new growth began to successfully differentiate, re-filling fractures and adhering tightly to the bones surface

“We believe that the specific nanoclay materials we use provide the required mineral composition, and give rise to the transformation of stem cells to bone tissue,” Alireza Dolatshahi-Pirouz says

Clinical trials are ongoing in Spain.


 

Myocardial infraction i.e. heart attacks still remain one of the leading causes of death in the world. Inflammation, deformation and injury of the heart both before and after a heart attack require substantial treatment using a very specific tool-set composed of the same aforementioned biomaterial scaffolds.

Stem cells can regenerate heart tissue alone, but the treatment has not passed all clinical trials yet.

Hydrogels can be administered for cardiac repair, through either epicardial, intracoronary, or endocardial injection.

Animal trials have proven stem cell-embedded hydrogels effective in the treatment of myocardial infarction by attenuating ventricular remodeling and inflammation of the heart while also improving ejection fraction and reducing scar size.

A recent clinical trial found that patients with a history of severe heart failure respond well to an alginate-based hydrogel, combined with standard therapy, improving their peak VO2 and time in a 6-min walk test after half a year of therapy, which proves that hydrogel-based therapies can be used to treat heart failure patients.

Scientists utilized several different compounds to construct hydrogel scaffolds including chitosan, collagen, decellularized tissues, fibrin, hyaluronic acid, keratin, Matrigel. Synthetic polymers composed of either polyethylene glycol or poly(N-isoproylacrylaminde are also being tested.


 

Filipe Pereira, a researcher from Swedish Lund University has succeeded in transforming human skin cells into blood stem cells as part of an international collaboration.

“This is a first step on the way to generating fully functional blood stem cells in a petri dish which, in the future, could be transplanted into patients with blood diseases”, says Filipe Pereira, the researcher from Lund University in Sweden who led the study now published in Cell Reports

“Skin cells are easily accessible and simple to reproduce in test tubes, which means that they could constitute an unlimited source of cells for transplantation. Blood stem cells, on the other hand, lose important properties when they are cultivated. This is why we wanted to investigate whether it was possible to use skin cells as material to produce blood stem cells”, says Filipe Pereira, researcher at Lund University and in charge of the international collaboration between Swedish, American, Russian and Portuguese researchers.

Blood stem cells are usually extracted from the patients own body or a genetically compatible donor. Either method is prone to unreliability based on the nature of the disease or availability of compatible donors. The newly discovered method can generate blood stem cells irregardless of such complications and the whole process takes anywhere between 15 and 25 Days.

First scientists experimented with different proteins in mice that regulate genetic expression, controlling the cells identity as far as what tissue they become. They eventually located three proteins that successfully convert mouse skin cells into blood stem cells.

Using the same combination of human proteins scientists were able to activate genes that enable human skin cells to transform into blood stem cells. One of the proteins called GATA2 lead the process – guiding the other two proteins around relevant parts of the genome.

“It is interesting that just three proteins can cause such a major change. The same transcription factors work in both mice and humans, showing that their combined function has been preserved through evolution”, says Filipe Pereira.

“When we transplanted the new blood stem cells into mice, we observed that the cells survived over three months. The next step will be to improve their capacity to regenerate blood production long-term. We now know much more about the underlying mechanisms of this process which will allow us to make this a reality in the future”, says Filipe Pereira

Researchers claim that the new treatment is suitable for helping victims of blood disease, such as leukaemia generate new, healthy blood cells.


Scientists from Case Western Reserve University School of Medicine report on new, more efficient method for producing myelin from brain stem cells. Myelin are a whitish layer of cells that form a protective sheathe around nerve fibers, enabling communication between neurons.

Generating different tissues in the brain with stem cells is not particularly new, back in August scientists came up with a new method for growing astrocytes.

“Making these specialized brain stem cells on a large scale at high purity from pluripotent stem cells gives us a powerful tool to study previously inaccessible normal and diseased tissues in the central nervous system,” said the senior author of the two papers, Paul Tesar, PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and associate professor of genetics and genome sciences at Case Western Reserve University School of Medicine. “We applied our technology to genetic models of myelin disease, which resulted in the discovery of a chemical compound that helps diseased myelin-producing cells to survive.”

First author Angela Lager, PhD, and colleagues have come up with a way to produce a bunch of of oligodendrocytes, which form Myelin, as well as their progenitor cells, called oligodendrocyte progenitor cells or OPC for short – from a mix of mouse embryonic stem cells and induced pluripotent stem cells. The team was able to produce oligodendrocytes from pluripotent stem cells that originate from any genetic background – offering a certain degree of accessibility not possible until now.

The treatment offers hope to millions of people suffering from diseases of myelin such multiple sclerosis, spinal cord injury, and schizophrenia.

Their research was published in the September issue of Nature Communications and Stem Cell Reports


Researchers narrow in on the exact protein responsible for invoking the incredible growth of queen bees after they’ve been coated in royal jelly. After exposing the protein to embryonic stem cells they were able to prevent the stem cells from differentiating, which is key to preserving them for medical purposes.

The experiment was led by assistant professor of dermatology Kevin Wang and performed at Stanford University.

Royalactin is the name of a protein that scientists suspected was the most important ingredient in royal jelly. To see if they could find similarities between how bees and animals react to royalactin they exposed mice embryonic stem cells to the protein.

“For royal jelly to have an effect on queen development, it has to work on early progenitor cells in the bee larvae,” Wang says. “So we decided to see what effect it had, if any, on embryonic stem cells.”

Researchers discovered that some amazing effects of royalactin were transferable to mammals, in this case – a mouse. By exposing the protein to embryonic stem cells from mice they were able to maintain the embryonic state for up to 20 generations longer without having to use inhibitors

“This was unexpected,” Wang said. “Normally, these embryonic stem cells are grown in the presence of an inhibitor called leukemia inhibitor factor that stops them from differentiating inappropriately in culture, but we found that royalactin blocked differentiation even in the absence of LIF.”

Luckily for us there is a protein in humans equivalent to royalactin called NHLRC, and it is produced during embryonic development. So researchers performed the same study on mouse embryonic stem cells using NHLRC instead of royalactin and achieved similar results. Suitably, they renamed the protein Regina, which is Latin for queen.

The ultimate conclusion is that Regina could be used to more inexpensively preserve embryonic stem cells for longer periods of time.

Their research was published in the journal Nature Communications.

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Sources

Turning stem cells into bone with nanoclay-reinforced hydrogel

Scientists develop new method to more efficiently generate brain stem cells

Mechanism for turning skin cells into blood stem cells uncovered

Bioactive scaffolds in stem-cell-based therapies for cardiac repair: protocol for a meta-analysis of randomized controlled preclinical trials in animal myocardial infarction models

Queen bee’s secret sauce uncovers a key ingredient that keeps stem cells young

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