mesenchymal stem cells

Pregnant women’s stem cells could help battle brittle bone diseases like osteoporosis

/ Kevin McCormack / Leave a comment

pregnant

Sometimes I wonder how a scientist ever came up with an idea for a potential treatment. Case in point is a study in the journal Scientific Reports, where researchers use stem cells from the amniotic fluid of a pregnant woman to cure osteoporosis in mice! What researcher, seeing a pregnant woman, thought to her or himself “I wonder if…..”

Regardless of how they came up with the idea, we might be glad they did because this study showed that those stem cells could reduce the number of fractures in mice with brittle bone disease by 78 percent. And that’s raising hopes they might one day be able to do the same for people.

Researchers at University College London took mesenchymal stem cells (MSCs) that had been shed by babies into the amniotic fluid of their mother, and injected them into mice with brittle bone disease. Previous studies had suggested that MSCs, taken at such an early age, might be more potent than similar cells taken from adults. That certainly seems to have been the case here where the treated mice had far fewer fractures than untreated mice.

Pascale Guillot, the lead researcher of the study, told the Guardian newspaper:

“The stem cells we’ve used are excellent at protecting bones. The bones become much stronger and the way the bone is organised internally is of much higher quality.”

 

What was also interesting was not just what they did but how they did it. You might think that the injected stem cells helped reduce fractures by forming new bones. You might think that, but you’d be wrong. Instead, the stem cells seem to have worked by releasing growth factors that stimulated the mouse’s own bone cells to kick into a higher gear, and help build stronger bones.

In the study the researchers say using MSCs from amniotic fluid has a number of distinct advantages over using MSCs from adults:

  • They are easier to expand into large numbers needed for therapies
  • They don’t create tumors
  • The body’s immune system won’t attack them
  • They are smaller and so can move around with greater ease
  • They are easier to reprogram into different kinds of cells

Next Guillot and his team want to explore if this approach could be used to treat children and adults with brittle bone disease, and to help adults with osteoporosis, a problem that affects around 44 million people in the US.

 “The discovery could have a profound effect on the lives of patients who have fragile bones and could stop a large number of their painful fractures.”

Stem cell stories that caught our eye: fashionable stem cells, eliminating HIV, cellular Trojan horse fights cancer

/ Karen Ring / 1 Comment

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cell fashion for a cause. Science and art are not mutually exclusive subjects. I know plenty of scientists who are talented painters or designers. But you don’t often see science being displayed in an artistic way or art being used to help explain complex scientific topics. I think that in the future, this will change as both subjects have a lot to offer one another.

Stem cell ties are in fashion!

Stem cell ties are in fashion!

Take this story from the University of Michigan for instance. Designer Dominic Pangborn has joined forces with the Heinz C. Prechter Bipolar Research Fund at the University of Michigan (UOM) to design fashionable scarves and ties featuring beautiful pictures of stem cells. The goal of the Prechter Fund scarf and tie project is to raise awareness for mental health research.

The scarves and ties feature pictures of brain stem cells taken by UOM scientists who are studying them to understand the mechanisms behind bipolar disorder. These stem cells were generated from induced pluripotent stem cells or iPS cells that were derived from donated skin biopsies of patients with bipolar disease. Studying these diseased brain cells in a dish revealed that the nerve cells from bipolar patients were misbehaving, sending out electrical signals more frequently compared to healthy nerve cells.

Dr. Melvin McInnis, the Prechter Fund research director, explained:

“By understanding the causes of bipolar disorder, we will be able to develop new treatments for the illness and most importantly, we’ll be able to prevent destructive mood episodes. Our ultimate goal is to allow people to live happy, normal lives.”

Pangborn is passionate about using art to reflect an important cause.

“I decided to add butterflies to the design because they signify metamorphosis. Our society is finally at a point where mental illness is openly talked about and research is taking a turn for the better.”

He plans to release his collection in time for National Mental Health Awareness month in May. All proceeds will go to the Prechter bipolar research projects at UOM.

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

Dr. Melvin McInnis, left, and Dominic Pangborn in the Pangborn Design Store in Ann Arbor. (UOM)

New stem cell therapy could eliminate HIV for good

The stem cells therapies being developed to cure HIV are looking more promising every day. A few are already being tested in clinical trials, and CIRM is funding two of them (you can read more about them here). News came out this week about a new trial conducted at the City of Hope’s CIRM Alpha Stem Cell Clinic. They reported in a news release that they’ve treated their first patient. His name is Aaron Kim, and he’s had HIV since he was born. In 1983, he and his twin sister were born prematurely and due to a complication, Aaron had to get a blood transfusion that unfortunately gave him HIV.

Aaron Kim with nurse. (City of Hope)

Aaron Kim with nurse. (City of Hope)

Aaron thought he would live with this disease the rest of his life, but now he has a chance at being cured. In March, Aaron received a transplant of his own bone marrow stem cells that were genetically engineered to have a modified version of the CCR5 gene that makes his cells resistant to HIV infection. CCR5 is a is a protein receptor on the surface of blood cells that acts as a gateway for HIV entry. The hope is that his reengineered stem cells will populate his immune system with HIV-resistant cells that can eliminate the virus completely.

Dr. John Zaia who is the director the the City of Hope Alpha Clinic explained,

“The stem cell therapy Aaron received is one of more than 20 cure strategies for HIV. It may not cure him, but our goal is to reduce or even halt Aaron’s reliance on HIV drugs, potentially eliminating the virus completely.”

My favorite part of this story was that it acknowledged how importance it is for patients to participate in clinical trials testing promising new stem cell therapies where the outcomes aren’t always known. Brave patients such as Aaron make it possible for scientists to make progress and develop better and safer treatments for patients in the future.

Dr. Zaia commented, “It’s a wonderful and generous humanitarian gesture on Aaron’s part to participate in this trial.”

Stem cell Trojan horse fights cancer

Chemotherapy is great at killing cancer cells, but unfortunately, it’s also great at killing healthy cells too. To combat this issue, scientists are developing new delivery methods that can bring high doses of chemotherapy drugs to the cancer tumors and minimize exposure of healthy tissues.

Mesenchymal stem cells loaded with drug-containing microparticles. Credit: Jeff Karp and Oren Levy, Brigham and Women's Hospital

Mesenchymal stem cells loaded with drug-containing microparticles.
Credit: Jeff Karp and Oren Levy, Brigham and Women’s Hospital

A study published this week in Biomaterials, describes a new drug delivery method that has the potential to be an effective treatment for prostate cancer. Researchers from the Brigham and Women’s Hospital and Johns Hopkins University developed a drug delivery platform using mesenchymal stem cells. They packaged a non-active, prodrug version of a potent prostate cancer chemotherapy drug into microparticles that they loaded into MSCs. When the MSCs and prostate cancer cells were cultured together in a dish, the MSCs released their prodrug cargo, which was then internalized by the prostate cancer cells. The prodrug was then metabolized into its active, cancer-killing form and was very effective at killing the cancer cells.

In a news release picked up by Science Daily, one of the lead scientists on the study, Dr. Oren Levy, further explained the stem cell Trojan horse concept:

“Mesenchymal stem cells represent a potential vehicle that can be engineered to seek out tumors. Loading those cells with a potent chemotherapeutic drug is a promising cell-based Trojan horse approach to deliver drugs to sites of cancer.”

If all goes well, the teams plan to develop different versions of their stem cell-based drug delivery method that target different cancers and other diseases.

Students use a 3D printer to sink their teeth into stem cell research

/ Kevin McCormack / Leave a comment

Student winners

L-R Alan Tan, Sid Bommakanti, Daniel Chae – prize winning science students

A 3D printer, some old teeth, and some terrific science were enough to help three high school students develop a new way of growing bone and win a $30,000 prize in a national competition.

The three teamed up for the Siemens Competition in Math, Science & Technology, which bills itself as “the nation’s premier research competition for high school students”.

The trio includes two from the San Francisco Bay area, where we are based; Sid Bommakanti from Amador Valley High School in Pleasanton, and Alan Tan, from Irvington High School in Fremont. The third member of the team, Daniel Chae, goes to Thomas Jefferson High School for Science and Technology in Alexandria, Virginia.

The three used mesenchymal stem cells – which are capable of being turned into muscle, cartilage or bone – which they got from the dental pulp found in wisdom teeth that had been extracted.

In a story posted on the KQED website Tan says they thought it would be cool to take something that is normally thrown away, and recycle it:

“When we learned we could take stem cells from teeth—it’s actually part of medical waste—we realized could turn this into bone cells,”

The students used a 3D printer to create a kind of scaffold out of a substance called polylatctic acid – it’s an ingredient found in corn starch or sugar cane. The scaffold had a rough surface, something they hoped would help stimulate the dental pulp to grow on it and become bone.

That’s what happened. The students were able to show that their work produced small clusters of cells that were growing on the scaffold, cells that were capable of maturing into bone. This could be used to create dental implants to replace damaged teeth, and, according to Alan Tan, to repair other injuries:

“We used dental pulp stem cells so that we could regenerate bones in various parts of our body so for example we could fix bones in your jaw and tibia and other places.”

The beauty of this approach is that the scaffold and bone could be implanted in, say, the mouth and then as the scaffold disintegrates the new bone would be left in place.

While they didn’t take the top prize (a $100,000 scholarship) they did have to see off some serious competition from nearly 1,800 other student project submissions to win a Team scholarship award.

The students say they learned a lot working together, and encouraged other high school students who are interested in science to take part in competitions like this one.

Sid Bommakanti “Both me, Alan and our other partner are interested in medicine as a whole and we wanted to make an impact on other people’s lives.”

Alan Tan: “I would say get into science early. Don’t be afraid to put yourself out there and talk to professors, talk to people, competitions like this are beneficial because they encourage students to get out there and interact with the real world.”

CIRM is helping students like these through its Stem Cell Education Portal,  which includes the materials and resources that teachers need to teach high school students about stem cells. All the materials meet both state and federal guidelines.

 

 

Cell survival strategy gives mesenchymal stem cells their “paramedic” properties

/ Todd Dubnicoff / 3 Comments
Electron micrograph of a human mesenchymal stem cells (Credit: Robert M. Hunt)

Electron micrograph of a human mesenchymal stem cells (Image credit: Robert M. Hunt)

A cell for all therapies
Type “mesenchymal stem cells” into the federal online database of registered clinical trials, and you’ll get a sprawling list of 527 trials testing treatments for diabetes, multiple sclerosis as well as diseases of the kidney, lung, and heart, to name just a few. Mesenchymal stem cells (MSCs) have the capacity to specialize into bone, cartilage, muscle and fat cells but their popularity as a therapeutic agent mostly comes from their ability to reduce inflammation and to help repair tissues.

MSCs may be great tools for scientists to fight disease, but what is it about their natural function that make MSCs – as UC Davis researcher Jan Nolta likes to calls them – the body’s “paramedics”? A fascinating study reported yesterday in Nature Communications by scientists at the Florida campus of The Scripps Research Institute (TSRI) and the University of Pittsburgh suggest that it’s a trait the cells gain as a result of their complex cell survival mechanisms.

The TSRI team came to this conclusion by studying how MSCs respond to oxygen-related stress. MSCs reside in the bone marrow where they help maintain and regulate blood stem cells. The bone marrow is naturally a hypoxic, or low oxygen, environment. Growing MSCs in the lab at oxygen levels found in the air we breathe are much higher than what is found in the marrow. This creates oxidative stress in which the excess oxygen leads to unwanted chemical reactions which disrupt a cell’s molecules.

One cell’s trash is another’s treasure
One result of this oxidative stress is damage to the MSCs’ mitochondria, structures responsible for generating the energy needs of a cell. The team found that MSCs package the faulty mitochondria into sacs, or vesicles, which travel to the cell surface to be dumped out of the cell. At this point, another resident of the bone marrow comes into the picture: the macrophage. Previous research has shown that macrophages and MSCs work closely together to maintain the health of the blood stem cells in the bone marrow.

Screen Shot 2015-11-04 at 9.58.48 AM

White arrow shows vesicles (red) carrying mitochondra (green) to the surface of the MSC  and being ingested by a macrophage (round shape in lower half) – (From Fig 2 Nat Commun. 2015 Oct 7;6:8472)

In a high oxygen stress environment, the team observed that MSCs can recruit macrophages to engulf the damaged mitochondria-containing vesicles and repurpose them for their own use. In fact, the researchers measured improved energy production in the macrophages after ingesting the MSCs’ mitochondria. Blocking the transfer of the damaged mitochondria from MSCs to macrophages caused the MSCs to die, confirming that this off-loading of mitochondria to macrophages is critical for MSC survival.

Evolving tricks for cell survival
Macrophages (macro=big; phages=eaters), key players of the immune system and the inflammation response, also rid the body of invading bacteria or damaged cells by devouring them. To avoid being swallowed up by the macrophage while donating its mitochondria, the stressed MSCs have another trick up their sleeve. The research team identified the release of other vesicles from the MSCs that contain molecules called microRNAs which stimulate anti-inflammatory properties in the macrophages. This prevented the macrophages from attacking and eating the MSCs.

And there you have it: as a result of relying on macrophages to survive stressful environments, MSCs appear to have evolved anti-inflammatory activities that turn out to be a handy tool for numerous ongoing and future cell therapy trials.

In a TSRI press release picked up by Newswise, professor Donald Phinney co-leader of study points out the groundbreaking aspect of the study:

Donald G. Phinney

Donald Phinney (photo: TSRI)

“This is the first time anyone has shown how mesenchymal stem cells provide for their own survival by recruiting and then suppressing normal macrophage activity.”