Repairing stroke-damaged rat brains

Now YOU just need to insist that your incompetent doctors and stroke hospitals  get human testing going.  Or YOU get every leader in that stroke hospital fired starting with the board of directors.   

I still prefer handing your doctor a pee cup and asking for stem cells in return.  It has only been 8 years, where the fuck is your doctor's protocol on turning urine into stem cells?

Turning urine into brain cells could help fight Alzheimer’s, Parkinson’s

December 2012

Oops, I'm not playing by the polite rules of Dale Carnegie,  'How to Win Friends and Influence People'. 

Politeness will never solve anything in stroke. Yes, I'm a bomb thrower and proud of it. Someday a stroke "leader" will ream me out for being truthful by making them look bad, I look forward to that day. 

The latest here:

Repairing stroke-damaged rat brains

Date:

April 8, 2020

Source:

Lund University

Summary:

Researchers have succeeded in restoring mobility and sensation of touch in stroke-afflicted rats by reprogramming human skin cells to become nerve cells, which were then transplanted into the rats' brains.

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Stroke in brain concept illustration (stock image).

Credit: © peterschreiber.media / Adobe Stock

Researchers at Lund University in Sweden have succeeded in restoring mobility and sensation of touch in stroke-afflicted rats by reprogramming human skin cells to become nerve cells, which were then transplanted into the rats' brains. The study has now been published in the Proceedings of the National Academy of Sciences (PNAS).

"Six months after the transplantation, we could see how the new cells had repaired the damage that a stroke had caused in the rats' brains," says Professor Zaal Kokaia, who together with senior professor Olle Lindvall and researcher Sara Palma-Tortosa at the Division of Neurology is behind the study.
Several previous studies from the Lund team and others have shown that it is possible to transplant nerve cells derived from human stem cells or from reprogrammed cells into brains of rats afflicted by stroke. However, it was not known whether the transplanted cells can form connections correctly in the rat brain in a way that restores normal movement and feeling.

"We have used tracking techniques, electron microscopy and other methods, such as light to switch off activity in the transplanted cells, as a way to show that they really have connected correctly in the damaged nerve circuits. We have been able to see that the fibres from the transplanted cells have grown to the other side of the brain, the side where we did not transplant any cells, and created connections. No previous study has shown this," says Zaal Kokaia, who, even though he and colleague Olle Lindvall have studied the brain for several decades, is surprised by the results.

"It is remarkable to find that it is actually possible to repair a stroke-damaged brain and recreate nerve connections that have been lost. The study kindles hope that in the future it could be possible to replace dead nerve cells with new healthy nerve cells also in stroke patients, even though there is a long way to go before achieving that," says Olle Lindvall.
The researchers have used human skin cells that have been reprogrammed in the laboratory to become nerve cells. They were then transplanted into the cerebral cortex of rats, in the part of the brain that is most often damaged after a stroke. Now the researchers will undertake further studies.
"We want to know more about how the transplanted cells affect the opposite hemisphere of the brain. We also want to take a closer look at how a transplant affects intellectual functions such as memory. In addition, we will study possible side effects. Safety is, of course, extremely important for cell transplantation if it is going to be used clinically in the future," says Zaal Kokaia.

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Story Source:
Materials provided by Lund University. Note: Content may be edited for style and length.

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Journal Reference:

1. Sara Palma-Tortosa, Daniel Tornero, Marita Grønning Hansen, Emanuela Monni, Mazin Hajy, Sopiko Kartsivadze, Sibel Aktay, Oleg Tsupykov, Malin Parmar, Karl Deisseroth, Galyna Skibo, Olle Lindvall, Zaal Kokaia. Activity in grafted human iPS cell–derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior. Proceedings of the National Academy of Sciences, 2020; 202000690 DOI: 10.1073/pnas.2000690117

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Lund University. "Repairing stroke-damaged rat brains." ScienceDaily. ScienceDaily, 8 April 2020. www.sciencedaily.com/releases/2020/04/200408102150.htm.

From skin to brain: Stem cells without genetic modification

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain. 
https://m.phys.org/news/2017-03-skin-brain-stem-cells-genetic.html
The practical implications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient's own cells.
"It's actually quite remarkable that it happens," says Stelios T. Andreadis, PhD, professor and chair of UB's Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.
The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.
Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.
"In medical applications this has tremendous potential because you can always get a skin biopsy," Andreadis says. "We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources."

Keratinocyte-derive neural crest stem cells that have been turned into neurons. Credit: University at Buffalo.

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. "It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition," Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB's School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.
Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.
"He is an excellent and persistent student," Andreadis says. "Most students would have given up." Andreadis also credits a seed grant from UB's office of the Vice President for Research and Economic Development's IMPACT program that enabled part of the work.
The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson's-like symptoms in a mouse model of hypomyelinating disease.
"This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further," Andreadis said.
The research is described in the journal Stem Cells under the title "Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates."

Nearly complete human brain grown in US lab: scientist

But not written up in a reputable journal with peer review, so beware.
http://news.yahoo.com/nearly-complete-human-brain-grown-us-lab-scientist-143316655.html
An almost complete version of a tiny human brain has been grown in a US lab in a move that could bring major strides to the treatment of neurological diseases, a scientist says.

Rene Anand, a professor at Ohio State University, has grown in a dish a brain equal in maturity to that of a five-week-old fetus, his university reported.

"It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain," Anand said.

Around the size of a pea, the brain in a lab dish includes multiple cell types, all major regions of the brain and a spinal cord, but lacks a vascular system, the university said.

It was grown from human skin cells and is claimed to be the most complete brain of its type grown yet.

Anand presented his research at a military health event in Florida on Tuesday.

Major scientific advances are usually published in peer-reviewed journals, where the claims are assessed independently before they are made public.

Anand and a colleague have co-founded an Ohio start-up company to commercialize the brain growth system, according to the university.
Anand expects the grown brain will allow easier and more ethical testing of drugs' effects on the mind, as scientists seek cures for brain disease and nervous system disorders, the school said.
"The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents," Anand said in a university report on his research.

It could also be a boon for general neuroscience research as the brain allows a hands-on approach to genome studies rather than computer models currently used.

"Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system –- you need a human brain," he said.

Skin may helps spot Alzheimer's and Parkinson's disease

And with this early detection our doctors will have to come up with some prevention protocols. But they won't, you'll have to figure this out on your own. Do not follow my ideas, they are not clinically proven.

My complete list here: Don't listen to me, your doctor obviously knows more than I do. Have him/her prove that knowledge or fire them.
Dementia prevention 19 ways

Skin may helps spot Alzheimer's and Parkinson's disease 

Scientists convert human skin cells directly into brain cells

So whom is going to take on the challenge of testing this in humans? ASA? NSA? WSO? None of these will because all they are is press release organizations. So if you have a spare 10 million or so you can hire your own researchers to do this. That is the only way this will get done in the next 30 years.
Or maybe you'd rather support these other neuron creation ideas;
So many places to get stem cells from;

1.  brain biopsies 

2.  Blood

3.  Bone marrow stem cells

4.  Skin cells 

5.  Re-programme other cells to become nerve cells, directly in the brain. 

6.  UK scientists use 3D printer to print human stem cells

7.  Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection

8.  Fat cells 

9.  Urine 

10.  Bone marrow
11.  Placenta
12.  Umbilical cord blood
13.  hair follicles
14.  menstrual blood
15.   liver cells
16.  Dental pulp

17.  Stem Cell Scaffolding

18.  Converting fibroblasts into functional neurons 

19.  Cells grown from the lining of their nose.

 

Scientists convert human skin cells directly into brain cells
The study is unusual because, unlike many cell conversion techniques, the cells did not return to a stem cell stage first - they converted directly into brain cells - thus avoiding the risk of producing many other types of cells.
And the study is unique, because the team managed to reprogram the skin cells to become a particular type of brain cell instead of a range of brain cells.
Writing in the journal Neuron, researchers from Washington University School of Medicine in St. Louis (WUSTL), MO, report how they used a particular combination of microRNAs and transcription factors to reprogram the skin cells into a particular type of brain cell known as medium spiny neurons.

More at link.

Breakthrough process turns skin cells into protective brain cells

If myelin is destroyed as part of our strokes then this could be very useful to us.

The real title here:

Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells

Abstract

• Abstract
• Accession codes
• Author information
• Supplementary information

Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.

Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3 and Glial-Derived Neurotrophic Factor Enhance Angiogenesis in a Tissue-Engineered In Vitro Model

We need angiogenesis to support stem cells and migrating neurons to the damaged area. Ask your doctor to apply this to your recovery. Its going to take some intellect to transfer this knowledge from skin to the brain.
http://online.liebertpub.com/doi/abs/10.1089/ten.tea.2012.0745

ABSTRACT

Skin is a major source of secretion of the neurotrophic factors nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) controlling cutaneous sensory innervation. Beside their neuronal contribution, we hypothesized that neurotrophic factors also modulate the cutaneous microvascular network. First, we showed that NGF, BDNF, NT-3, and GDNF were all expressed in the epidermis, while only NGF and NT-3 were expressed by cultured fibroblasts, and BDNF by human endothelial cells. We demonstrated that these peptides are highly potent angiogenic factors using a human tissue-engineered angiogenesis model. A 40% to 80% increase in the number of capillary-like tubes was observed after the addition of 10 ng/mL of NGF, 0.1 ng/mL of BDNF, 15 ng/mL of NT-3, and 50 ng/mL of GDNF. This is the first characterization of the direct angiogenic effect of NT-3 and GDNF. This angiogenic effect was mediated directly through binding with the neurotrophic factor receptors tropomyosin-receptor kinase A (TrkA), TrkB, GFRα-1 and c-ret that were all expressed by human endothelial cells, while this effect was blocked by addition of the Trk inhibitor K252a. Thus, if NGF, BDNF, NT-3, and GDNF may only moderately regulate the microvascular network in normal skin, they might have the potential to greatly increase angiogenesis in pathological situations.

Skin Cells Turned Into Brain Cells in Lab Study

So lets keep testing this for stroke, there would be lots of volunteers. 

Skin Cells Turned Into Brain Cells in Lab Study

  Scientists who reprogrammed skin cells into brain cells say their research could lay the groundwork for new ways to treat Alzheimer's and other brain diseases.
The team at the Gladstone Institutes in San Francisco transferred a gene called Sox2 into both mouse and human skin cells. Within days, the skin cells transformed into early-stage brain stem cells called induced neural stem cells.
These cells began to self-renew and soon matured into neurons capable of transmitting electrical signals. Within a month, these new neurons had developed into neural networks, according to the research published online June 7 in the journal Cell Stem Cell.

Brain tissue created from human skin

This joins the ones from menstrual blood, fat cells, hair follicles, dental pulp, bone marrow, or liver cells. Ask your researcher which one shows the most promise.
http://www.canberratimes.com.au/news/world/world/general/brain-tissue-created-from-human-skin/2452497.aspx
British scientists are claiming a major breakthrough after creating brain tissue from human skin.
The researchers have for the first time generated a crucial type of brain cells in the laboratory by reprogramming skin cells.
They say it could speed up the hunt for new treatments for conditions such as Alzheimer's disease, epilepsy and stroke.
Until now it has only been possible to generate tissue from the cerebral cortex, the area of the brain where most major neurological diseases occur, by using controversial embryonic stem cells, obtained by the destruction of an embryo.
This has meant the supply of brain tissue available for research has been limited due to ethical concerns and limited availability.
Scientists at the University of Cambridge show for the first time that it is possible to re-program adult human skin cells so they develop into neurons found in the cerebral cortex.
Initially, brain cells grown in this way could be used to help researchers gain a better understanding of how the brain develops.
Also, it shows what goes wrong when it is affected by disease.
They could also be used for screening new drug treatments.
Eventually, scientists hope the cells could be used to provide healthy tissue that can be implanted into patients to treat neurodegenerative diseases and brain damage. Rick Livesey, who led the research at the university's Gurdon Institute, said: ''The cerebral cortex makes up 75 per cent of the human brain. It is where all the important processes that make us human take place. It is, however, also the major place where disease can occur.
''We have been able to take reprogrammed skin cells so they develop into brain stem cells and then essentially replay brain development in the laboratory.
''We can study brain development and what goes wrong when it is affected by disease in a way we haven't been able to before. We see it as a major breakthrough in what will now be possible.''
The cerebral cortex is the part of the brain that is responsible for most of the high-level thought processes such as memory, language and consciousness.