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KIDNEY BREAKTHROUGH: COMPLETE LAB GROWN ORGAN WORKS IN RATS

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on April 19, 2013 at 4:00 pm
A brand new rat kidney being built on the scaffold of an old one <i>(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)</i>

A brand new rat kidney being built on the scaffold of an old one

(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)

Kidney breakthrough: complete lab-grown organ works in rats

 

  • 18:00 14 April 2013 by Andy Coghlan

 

For the first time, complete lab-grown kidneys have been successfully transplanted into rats, filtering and discharging urine as a normal kidney would.

 

The breakthrough paves the way for human-scale versions, which could potentially provide an inexhaustible supply of organs, eliminating the need for recipients to wait for a matching donor kidney Movie Camera.

 

Similar techniques have already been applied successfully in people with simpler tissue, such as windpipes. But the kidney is by far the most complex organ successfully recreated.

 

“If this technology can be scaled to human-size grafts, patients suffering from renal failure, who are currently waiting for donor kidneys, could theoretically receive an organ grown on demand,” says Harald Ott, head of the team that developed the rat kidneys at the Massachusetts General Hospital in Boston.

 

“In an ideal world, such grafts could be produced from patient-derived cells, enabling us to overcome both donor organ shortages and the need for long-term immunosuppression drugs,” says Ott. Currently in the US alone, 18,000 transplants are carried out each year, but 100,000 Americans remain on waiting lists.

 

Strip and coat

 

To make the rat kidneys, Ott and his colleagues took kidneys from healthy “donor” rats and used a chemical solution to wash away the native cells, leaving behind the organ’s scaffold. Because this is made of collagen, a biologically inert material, there is no issue of the recipient’s body rejecting it.

 

Next, the team set about regrowing the “flesh” of the organ by coating the inner surfaces of the scaffold with new cells. In the case of humans, these would likely come from the recipient, so all the flesh would be their own.

 

The kidney was too complex to use the approach applied to the windpipe – in which its scaffold was coated by simply immersing it in a bath of the recipient’s cells.

 

Instead, the team placed the kidney scaffolds in glass chambers containing oxygen and nutrients, and attached tubes to the protruding ends of the renal artery, vein and ureter – through which urine normally exits the kidney. They recoated the insides of the blood vessels by flowing human stem cells through the tubes attached to the artery and vein. Through the ureter, they fed kidney cells from newborn rats, re-coating the labyrinthine tubules and ducts that make up the kidney’s urine filtration system.

 

It took many attempts to establish the precise pressures at which to feed the cells into the organ, as if it was growing in an embryonic rat. Remarkably, given the complexity of the kidney, the cells differentiated into exactly those required in the different compartments of the organ. “We found the correct cell types homed in to specific regions in the organ matrix,” says Ott.

 

The kidneys, which took about a fortnight to fully recoat, worked both in the lab and when transplanted into rats. They filtered out and discharged urine, although they did not sieve it as well as a natural kidney would. Ott is confident that the function can be improved by refining the technique.

 

Humans and pigs

 

The team is now attempting the same procedure using human kidneys, and also pig kidneys, which could be used to make scaffolds if there were a scarcity of human donors. The team has already successfully repopulated pig kidneys with human cells, but Ott says further studies are vital to guarantee that the pig components of the organ do not cause rejection when transplanted into humans.

 

The fact that heart valves and other “inert” tissues from pigs are already successfully used in humans without rejection suggests that this will not be a big problem.

 

Other researchers working in the field hailed the team’s success at recreating such a complex organ. “The researchers have taken a technique that most in the field thought would be impossible for complex organs such as the kidney, and have painstakingly developed a method to make it work,” says Jamie Davies at the University of Edinburgh, UK, who was part of a team that last year made some headway in their attempts to grow kidneys from scratch in the lab. “By showing that recellularisation is feasible even for complicated organs, their work will stimulate similar approaches to the engineering of other body systems.”

 

Journal reference: Nature Medicine, DOI: 10.1038/nm.3154

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HHMI News: Stem Cells Recall Their Origins

In ALL ARTICLES on July 23, 2010 at 3:40 am

In 1983, Tom Cruise played the character ‘Stefan Djordjevic’ in the movie “All the Right Moves” opposite Lea Thompson.  In “All the Right Moves,” Mr Cruise plays “a headstrong high school football star who dreams of getting out of his small Western Pennsylvania steel town with a football scholarship.”  He is hampered by, among other things, his small town upbringing and meager origins.

https://i0.wp.com/img4.ifilmpro.com/blog//1/8/7/5/1875583/200901/1232660189436.jpg

It turns out, Mr Cruises’ character has something in common with Induced Pluripotent Stem Cells…they too are held back by where they came from and who they are/were.

“Dr. George Daley, director of the Stem Cell Transplantation Program at Children’s Hospital Boston and a Howard Hughes Medical Institute investigator, and colleagues reported in the journal Nature that iPS cells retain an “epigenetic memory” of their origins; they remember whether they came from skin or muscle or blood.” Via

[Epigenetic memory is a process by which changes in gene expression are passed on through mitosis or meiosis through factors other than DNA sequence.  Epigenetic memory in stem cells is a limiting factor…read: “not good.”]

Stem Cells Recall Their Origins – July 19, 2010

Cells, it turns out, remember where they came from. Four years ago, scientists made a breakthrough in stem cell research, when they discovered how to turn back the developmental clock on skin cells, muscle cells, and other “adult” cells so the cells would behave like embryonic stem cells. These induced pluripotent stem cells (iPS cells) were touted as an alternative to the ethically contentious embryonic stem cells.

Now, though, two groups of Howard Hughes Medical Institute researchers report that iPS cells retain a genetic memory of their tissue of origin. In a sense, the iPS cells “remember” that they came from skin, muscle, blood, and so on. This memory impedes the transformation of iPS cells into other types of cells, a prospect that has deep implications for researchers working with these kinds of cells, say HHMI investigator George Q. Daley and HHMI early career scientist Konrad Hochedlinger, who led the two research groups. The scientists worked independently but shared manuscripts and coordinated joint publications on July 19, 2010 in Nature (Daley) and Nature Biotechnology (Hochedlinger).

“But iPS [induced pluripotent stem cells] cells often don’t function as well as embryonic cells, and our new research offers an explanation as to why that is the case.” – George Q. Daley

Creating iPS cells is an important research tool because the technique can be used to generate disease-specific stem cell lines that, like embryonic stem cells, can develop into many cell types.

“The backdrop to this research is that a lot of people have the impression that iPS cells are the equivalent of embryonic stem cells,” says Daley. “That has been used as an argument that we do not need to keep studying embryonic stem cells. But iPS cells often don’t function as well as embryonic cells, and our new research offers an explanation as to why that is the case.”…

via HHMI News: Stem Cells Recall Their Origins.

Boston Scientific Corp. (BSX) suspend sales of medical devices that restore normal heart rhythm and manage heart failure

In BUSINESS OF STEM CELLS on March 15, 2010 at 8:01 pm

Pharma can’t seem to do anything right these days.  Falsified clinical trials, political agendas, now this. – dg

3rd UPDATE: Boston Scientific Slides On Halt Of ICD Sales

MARCH 15, 2010, 11:40 A.M. ET

Boston Scientific Corp. (BSX) suspended sales of medical devices that restore normal heart rhythm and manage heart failure, saying it failed to submit for U.S. regulatory approval certain changes in the way it makes the products.

The news sent Boston Scientific shares plunging 16% to $6.51 in recent trading. A big portion of the products affected–implantable cardioverter difibrillators, or ICDs, in the U.S.–represented about 15% of total company sales last year, and it’s not clear how long sales of the products will be suspended.

The documentation snafu is the latest setback for the Natick, Mass., company’s ICD business. Boston Scientific acquired Guidant in 2006 after reports of safety problems with Guidant’s ICDs, and Boston Scientific suffered years of negative fallout over the issue.

The news could also damage the credibility of the company’s new management team in the eyes of investors. “The announcement will weaken quality perception of a company that was on the brink of recovery,” Morgan Stanley analyst David Lewis wrote in a note.

On Monday, Boston Scientific said it stopped shipment and is retrieving inventory of all ICDs, as well as its cardiac resynchronization therapy defibrillators, or CRT-Ds. The company said it had found two instances of manufacturing changes that, while successfully validated, weren’t submitted to the U.S. Food and Drug Administration.

The errors put the company’s ICD devices out of compliance with FDA regulations, according to an analyst note from Bernstein Research. Boston Scientific said it plans to work closely with the FDA to resolve the situation, while saying it had no indications the manufacturing-process changes poses a risk to patients and it is not recommending that implanted devices be taken out…

Discovery aims to correct cellular defects leading to diabetes

In Doctors Practicing Excellence on January 5, 2010 at 3:49 am

Discovery Aims to Correct Cellular Defects Leading to Diabetes

ScienceDaily (Jan. 4, 2010) — A new research discovery published online in the FASEB Journal may change the perception and treatment of diabetes. That’s because scientists have moved closer toward correcting the root cause of the disease rather than managing its symptoms. Specifically researchers identified a protein (G6PD protein) and its antioxidant product (NAPDH) that both prevent the death and promote the growth of cells which produce and release insulin in the pancreas (beta cells).

“Abnormally high levels of oxidants are thought to be a major cause of diabetes and the complications of diabetes, as well as many other diseases,” said Robert C. Stanton, M.D., co-author of the study, from Joslin Diabetes Center in Boston. “By understanding the specific defects in processes that either produce too many oxidants or not enough antioxidants, a new era of highly specific, targeted treatments will emerge that very effectively treat or possibly prevent many of these diseases.”

via Discovery aims to correct cellular defects leading to diabetes.

Breathing Easier with Adult Stem Cells

In VICTORIES & SUCCESS STORIES on December 3, 2009 at 1:14 pm

Several recent reports, using animal models, provide evidence for treating lung disorders with adult stem cells.

Premature babies are often placed on ventilators to deliver oxygen and expand underdeveloped lungs, but the high oxygen and mechanical ventilation can lead to lung inflammation, inhibit proper lung growth, and lead to long-term complications. Work out of Children’s Hospital in Boston found that bone marrow stromal cells, a type of adult stem cell, can reduce inflammation in lung tissue. Using newborn mice as a model, the researchers injected adult bone marrow stem cells intravenously. The cells migrated to the lungs and prevented inflammation. The cells seem to work by secreting protective and stimulatory factors that help the lung cells and blood vessels; the same effects could be obtained by injecting the growth medium in which the adult stem cells had been grown. The results are published in the American Journal of Respiratory and Critical Care Medicine.

Similar results have been published by an international team, led by Canadian scientist Dr. Bernard Thébaud at the Stollery Children’s Hospital, Edmonton, Alberta. Using a rat model, the scientists found that adult stem cells from bone marrow could repair lung damage in newborn rats as well as prevent further damage. According to Dr. Thébaud:

“The really exciting thing that we discovered was that stem cells are like little factories, pumping out healing factors.”

These results are also published in the American Journal of Respiratory and Critical Care Medicine.

More breathable news comes from a team in South Korea led by Dr. Won Soon Park from the Samsung Medical Center. Using newborn laboratory rats with oxygen-deprived lung injury, the researchers found that mesenchymal stem cells, a type of adult stem cell from umbilical cord blood, had a protective effect against low-oxygen-induced lung injury. They noted that their findings could have important therapeutic potential for the currently untreatable hyperoxic neonatal lung disease, or bronchopulmonary dysplasia (BPD), in premature human infants. The easy availability of umbilical cord blood is also an associated benefit. The results are published in the journal Cell Transplantation.

And in a final breath of adult stem cell fresh air, a team at the University of Illinois at Chicago College of Medicine identified adult stem cells in the bone marrow of mice that could prevent and treat acute lung injury. The researchers discovered a way to grow and stimulate the adult stem cells, and when injected into mice with acute lung injury, the cells repaired the lung injury, prevented fluid build-up and improved survival of the mice. Results were published in the journal Stem Cells.

So take a deep breath in appreciation of adult stem cells.

via FRC Blog » Breathing Easier with Adult Stem Cells.

The Beauty of Stem Cells #3 – by Dr Douglas Cowan, Children’s Hospital Boston

In ALL ARTICLES on March 31, 2009 at 10:03 am

cowan_3-muscle-stem-cells

Muscle Stem Cells
(3 of 3)

By combining myoblasts and microcarriers in a bioreactor, researchers can greatly increase the number of stem cells. They can then easily separate them from the myoblasts.

The first three micrographs in this gallery show cells called myoblasts (a type of muscle cell) attached to spherical microcarriers. The microcarriers allow for the growth of the stem cells (shown in green), which, in this case, have been isolated from skeletal muscle. Photo: Douglas Cowan, Children’s Hospital Boston.

Photo: Douglas Cowan, Children’s Hospital Boston.

http://www.childrenshospital.org/research/cowan_gallery/photo3.html

The Beauty of Stem Cells #2 – by Dr Douglas Cowan, Children’s Hospital Boston

In ALL ARTICLES on March 31, 2009 at 9:59 am

cowan_2-muscle-stem-cells

Muscle Stem Cells
(2 of 3)

The first three micrographs in this gallery show cells called myoblasts (a type of muscle cell) attached to spherical microcarriers. The microcarriers allow for the growth of the stem cells (shown in green), which, in this case, have been isolated from skeletal muscle. Photo: Douglas Cowan, Children’s Hospital Boston.

http://www.childrenshospital.org/research/cowan_gallery/photo3.html

The Beauty of Stem Cells #1 – by Dr Douglas Cowan, Children’s Hospital Boston

In ALL ARTICLES on March 31, 2009 at 9:53 am

cowan_1-muscle-stem-cells

Muscle Stem Cells

(1 of 1)

Doug Cowan, PhD, is interested in understanding the molecular and cellular biology of the cardiovascular system. He is especially interested in using engineered tissue and stem cells to improve heart function.

This gallery of micrographs (photographs taken through a microscope) gives a sampling of the work taking place in Dr. Cowan’s laboratory.

The first three micrographs in this gallery show cells called myoblasts (a type of muscle cell) attached to spherical microcarriers. The microcarriers allow for the growth of the stem cells (shown in green), which, in this case, have been isolated from skeletal muscle. Photo: Douglas Cowan, Children’s Hospital Boston.

Photo: Douglas Cowan, Children’s Hospital Boston.

http://www.childrenshospital.org/research/cowan_gallery/images/cowan_1.htm/trackback/

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