Study Identifies Safer Stem Cell Therapies

To reject or not reject, that is the question facing the human immune system when new tissue or cells are transplanted into the body.

Stem cell-therapy promises hope for many debilitating diseases that currently have no cures. However, the issue of immune rejection has prompted scientists to carefully consider how to develop safe stem cell therapies that will be tolerated by the human immune system.

Before the dawn of induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) were suggested as a potential source for transplantable cells and tissue. However, ESCs run into a couple of issues, including their origin, and the fact that ESC-derived cells likely would be rejected when transplanted into most areas of a human due to differences in genetic backgrounds.

The discovery of iPSCs in the early 2000’s gave new hope to the field of stem cell therapy. By generating donor cells and tissue from a patient’s own iPSCs, transplanting those cells/tissue back into the same individual shouldn’t – at least theoretically – cause an immune reaction. This type of transplantation is called “autologous” meaning that the stem cell-derived cells have the same genetic background as the person.

Unfortunately, scientists have run up against a roadblock in iPSC-derived stem cell therapy. They discovered that even cells derived from a patient’s own iPSCs can cause an immune reaction when transplanted into that patient. The answers as to why this occurs remained largely unanswered until recently.

In a paper published last week in Cell Stem Cell, scientists from the University of California, San Diego (UCSD) reported that different mature cell types derived from human iPSCs have varying immunogenic effects (the ability to cause an immune reaction) when transplanted into “humanized” mice that have a human immune system. This study along with the research conducted to generate the humanized mice was funded by CIRM grants (here, here).

In this study, retinal pigment epithelial cells (RPE) and skeletal muscle cells (SMC) derived from human iPSCs were transplanted into humanized mice. RPEs were tolerated by the immune system while SMCs were rejected. (Adapted from Zhao et al. 2015)

Scientists took normal mice and replaced their immune system with a human one. They then took human iPSCs generated from the same human tissue used to generate the humanized mice and transplanted different cell types derived from the iPSCs cells into these mice.

Because they were introducing cells derived from the same source of human tissue that the mouse’s immune system was derived from, in theory, the mice should not reject the transplant. However, they found that many of the transplants did indeed cause an immune reaction.

Interestingly, they found that certain mature cell types derived from human iPSCs created a substantial immune reaction while other cell types did not. The authors focused on two specific cell types, smooth muscle cells (SMC) and retinal pigment epithelial cells (RPE), to get a closer look at what was going on.

iPSC-derived smooth muscle cells created a large immune response when transplanted into humanized mice. However, when they transplanted iPSC-derived retinal epithelial cells (found in the retina of the eye), they didn’t see the same immune reaction. As a control, they transplanted RPE cells made from human ESCs, and as expected, they saw an immune response to the foreign ESC-derived RPE cells.

RPE_1

iPSC derived RPE cells (green) do not cause an immune reaction (red) after transplantation into humanized mice while H9 embryonic stem cell derived RPE cells do. (Zhao et al. 2015)

When they looked further to determine why the humanized mice rejected the muscle cells but accepted the retinal cells, they found that SMCs had a different gene expression profile and higher expression of immunogenic molecules. The iPSC-derived RPE cells had low expression of these same immunogenic molecules, which is why they were well tolerated in the humanized mice.

Results from this study suggest that some cell types generated from human iPSCs are safer for transplantation than others, an issue which can be addressed by improving the differentiation techniques used to produce mature cells from iPSCs. This study also suggests that iPSC-derived RPE cells could be a safe and promising stem cell therapy for the treatment of eye disorders such as age-related macular degeneration (AMD). AMD is a degenerative eye disease that can cause vision impairment or blindness and usually affects older people over the age of 50. Currently there is no treatment for AMD, a disease that affects approximately 50 million people around the world. (However there is a human iPSC clinical trial for AMD out of the RIKEN Center for Developmental Biology in Japan that has treated one patient but is currently on hold due to safety issues.)

The senior author on this study, Dr. Yang Xu, commented on the importance of this study in relation to AMD in a UCSD press release:

Dr. Yang Xu

Dr. Yang Xu

Immune rejection is a major challenge for stem cell therapy. Our finding of the lack of immune rejection of human iPSC-derived retinal pigment epithelium cells supports the feasibility of using these cells for treating macular degeneration. However, the inflammatory environment associated with macular degeneration could be an additional hurdle to be overcome for the stem cell therapy to be successful.

Xu makes an important point by acknowledging that iPSC-derived RPE cells aren’t a sure bet for curing AMD just yet. More research needs to be done to address other issues that occur during AMD in order for this type of stem cell therapy to be successful.

 


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Stem cell stories that caught our eye: A groove for healing hearts, model for muscular dystrophy and the ice bucket worked

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.

A tight groove could help heal a heart.  We have written several posts with the theme “It takes a village to raise a stem cell.” If you want a stem cell to mature into a desired tissue you have to pay attention to all aspects of its environment—both the chemicals around it and the physical space.

A team at the Imperial College London has provided the latest chapter to this tale. It turns out if you want stem cells to consistently turn into long fibers of heart muscle, besides providing them with the right chemical signals making them grow in long narrow grooves on lab plate also helps. They got a two-fold increase in heart muscle cells compared to stem cells grown on a flat lab plate.

They’re now trying to figure out why the etched silicon chips worked so well for generating heart muscle. The journal Biomaterials and Regenerative Medicine published the work and the web portal myScience picked up the university’s press release.

Stem cell model for muscular dystrophy. In the past, when scientists have looked at muscle samples from patients with Duchenne muscular dystrophy (DMD) to see why they have the characteristic muscle weakening, they ‘ve arrived at the scene of the crime too late. At that point, the cellular missteps had already occurred and all that is left to observe was the damage.

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

So, a team at Kyoto University reprogrammed a patient’s cells to create iPS type stem cells. They then used genetic cues to direct the stem cells to become muscle and watched to see how what went wrong as this process happened.

“Our model allows us to use the same genetic background to study the early stage of pathogenesis which was not possible in the past,” said first author Emi Shoji.

The research published in Scientific Reports and highlighted in a university press release picked up by MedicalXpress documented the level of inappropriate influx of calcium into the cells and showed that a specific cell surface receptor channel was to blame. That receptor will now become a target for new drug therapy for DMD pateints.

Ice bucket results.  The ALS Association raised $220 million in the past year for amyotrophic lateral sclerosis, or Lou Gehrig’s disease, by getting people to dump bucket of ice water over their heads and then make a donation. More important, in just a year a major paper funded by the proceeds of the ice bucket challenge has shown a defect in the nerves of ALS patients and shown that correcting the defect makes the cells healthier. Those are pretty fast results for science.

In a paper published in the prestigious journal Science a team at Johns Hopkins found that one protein, TDP-43, was not doing its job well. When they genetically modified stem cell from ALS patients to correct that defect the cells worked properly. YahooFinance ran a story about the challenge and the new research.

“If we are able to mimic TDP-43’s function in the human neurons of ALS patients, there’s a good chance that we could slow down progression of the disease!” said Jonathan Ling, a researcher on the team. “And that’s what we’re putting all our efforts into right now.”

Of the initial $115 million raised during the early months of the challenge, 67 percent went to research, 20 percent to patient services, and nine percent to public and professional education. Just four percent went to overhead costs of fund raising.

China says it’s cracking down on clinics. I spend a considerable amount of time suggesting callers to our agency be very cautious about considering spending large sums of money to go overseas to get unregulated and unproven stem cell treatment. So, I was pleased to read this morning’s news that China’s top health authority issued regulation to control some of the most questionable clinics.

The regulations reported in China Daily note that any treatments using stem cells for conditions other than proven uses in blood diseases would be considered experimental and could only be conducted in approved hospitals. It noted conditions touted by clinics there including epilepsy, cerebral palsy, spinal cord injury and autism.

“Only eligible hospitals can perform the practice as a clinical trial for research purpose and it must not be charged or advertised. Anyone caught breaking the rules will be punished according to the new regulation,” said Zhang Linming, a senior official of the science and technology department of the commission.

Stem cell stories that caught our eye: potentially safer cell reprogramming, hair follicle cells become nerve and liver stem cells

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.

A potentially safer way to reprogram cells. Ever since then soon-to-be Nobel Prize winner Shinya Yamanaka showed how to reprogram adult cells to an embryonic stem cell-like state labs around the world have jumped on that band wagon. But many of their experiments have not just been using those cells but rather looking for ways to make them more efficiently and possibly safer for clinical use.

The four “Yamanaka factors” traditionally used to make what are now called induced pluripotent stem cells (iPSCs) include genes that can induce cancer. So, folks have been justifiably nervous about using cells derived from iPSCs in patients.

Today in the journal Science two different Chinese teams report slightly different methods of using only chemicals to reprogram skin cells directly into nerves. One team worked at the Shanghai Institutes for Biological Sciences and the other worked at Peking University.

“In comparison with using transgenic reprogramming factors, the small molecules that are used in this chemical approach are cell permeable; cost-effective; and easy to synthesize, preserve, and standardize; and their effects can be reversible,” Hongkui Deng of the Peking team said in a press release used to write a piece in the International Business Times.

 

Stem cells in hair follicles may repair nerve. The base of our hair follicles contains skin stem cells as you would expect, but it also contains cells with markers suggesting they come from the area of the embryo known as the neural crest. A team at the University of Newcastle in the U.K. tested those cells to see if they have stem cell properties and they do.

They were able to use those cells to create Schwann cells, support cells that our bodies use to repair nerves and help with certain systems like sensation. The team’s Schwann cells interacted with nerve cells in lab dishes the way natural cells do in the body.

“We observed that the bulge, a region within hair follicles, contains skin stem cells that are intermixed with cells derived from the neural crest – a tissue known to give rise to Schwann cells,” said Maya Sieber-Blum, in a university press release picked up by Yahoo. “This observation raised the question whether these neural crest-derived cells are also stem cells and whether they could be used to generate Schwann cells.”

They showed that the cells can indeed become Schwann cells. The researchers now want to see if their cells can repair nerve damage in an animal model.

Prior work at Stanford had turned embryonic stem cells into liver cells.

Prior work at Stanford had turned embryonic stem cells into liver cells.

Drink up. Liver stem cells found. The liver creates new liver cells quite readily, whether damaged by alcohol or other factors. But no one has known exactly where the new cells come from, with most researchers assuming the remaining health cells divide to create new tissue. But a team at Stanford suggested that the liver works too hard for that to be the case. In order to remove all the toxins that come its way adult liver cells have amplified certain chromosomes, and team leader Roel Nusse said that would make them unable to divide and create new cells.

So, his team set out to track down previously elusive liver stem cells. They bred mice that had cells that would have a green florescent glow if they carried a protein usually found only on stem cells. They indeed did find stem cells and tracked them as the animals matured and saw them both divide to create more stem cells and mature into adult liver cells.

“We’ve solved a very old problem,” said Nusse, who is a Howard Hughes investigator. “We’ve shown that like other tissues that need to replace lost cells, the liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease.”

The Hughes Institute issued a press release and the International Business Times wrote the story and illustrated it with a photo from CIRM’s Flickr site.

Earliest stem cells made in lab; provide “extraordinary” potential

Embryonic stem cells are classified as pluripotent cells because they are able (“potent”) to mature into almost every (“pluri”) cell type. Thanks to Nobel Prize winner Shinya Yamanaka, researchers have been able to reprogram fully matured cells, like skin or blood, into embryonic stem cell-like induced pluripotent stem cells (iPS). The technique has revolutionized stem cell science, providing human models of disease and the prospect of personalized cell therapies.

150805_totipotentst1cf4

Human embryo about to complete 1st cell division. Each of these cells are totipotent: they have the ability (“potent”) can give rise to all (“toti”) the cell types of the developing embryo including placenta and umbilical cord. (Image credit: The Endowment for Human Development)

And yet it has remained unknown if reprogramming cells resembling so-called totipotent cells is possible. Unlike iPS or embryonic stem cells, totipotent cells have complete shape-shifting abilities in that they can give rise to all (“toti”) the cell types of the developing embryo including the placenta and umbilical cord. They appear briefly during the earliest stages of development when the fertilized embryo is made up of just one or a few cells. Could lab-derived totipotent cells provide an equally or even more powerful research tool than iPS cells?

The stem cell field is now in position to ask that question. This week scientists from French Institute of Health and Medical Research (INSERM) and the Max Planck Institute in Germany report in Nature Structural Biology that they successfully induced mouse embryonic stem cells to take on totipotent characteristics.

150805_TotipotentBlog

That question mark over the blue arrow can be removed after this week’s report that pluripotent stem cells can be induced to take on characteristics of totipotent cells. (image credit: IGBMC)

To achieve this feat, the scientists started with the known observation that a small amount of totipotent cells spontaneously appear when growing pluripotent stem cells in petri dishes. They are called 2C-like cells because of their likeness to the cells of the two-cell embryo. The team isolated those 2C cells and carefully compared them to the pluripotent embryonic stem cells. They noticed the DNA in 2C cells had a looser structure, which indicates more flexibility to switch on many different genes in a cell. With this information, they found that a protein called CAF1 known to play a role in making a tighter DNA structure, and inhibiting genes, was reduced in the totipotent 2C cells.

By experimentally blocking the function of CAF1 in pluripotent cells, the tightened DNA structure was loosened, leading to more genes being switched on and inducing a totipotent state. With these cells in hand, the team can now examine their possible impact on accelerating progress in regenerative medicine. Maria-Elena Torres-Padilla, the lead scientist on the project, pointed out in a press release the significance of these cells for future studies:

“Totipotency is a much more flexible state than the pluripotent state and its potential applications are extraordinary.”

Mini-Brains Help Unlock Autism’s Secrets

Some diseases like sickle cell anemia, an inherited blood disorder, can be traced to a single known genetic mutation. But other diseases like autism spectrum disorder (ASD), are so varied in their symptoms and severity that pinpointing the underlying cause is extremely complicated. People with autism typically have difficulties communicating with the world around them, unable to fully process both verbal and non-verbal language, and plagued by repetitive behaviors. Some rare forms of autism appear to be inherited but over 80% of cases are idiopathic, a fancy term for “we don’t know what causes it.”

Process for making organoid

Process for making organoid “mini-brains” from iPS cells derived from patient skin samples (image credit: Keval Tilva, wikipedia)

Last week, a research team at the Yale School of Medicine published data in Cell that appears to unveil some of the mystery behind autism. The scientists relied on induced pluripotent stem cells (iPS) derived from skin samples of people with severe forms of ASD. Rather than maturing the stem cells into a flat layer of brain cells, or neurons, on a plastic petri dish, the Yale team stirred the cells in a bioreactor. This technique allows the cells to mature in a small three-dimensional clump, which self organizes into so-called brain “organoids” or “mini-brains.” The structure of these mini-brains resembles the portions of the developing fetal human brain, the stage at which autism is thought to arise.

An analysis of the mini-brains found no underlying genetic mutations. Instead, the team identified genes involved with cell growth and neuron development that were turned on higher in the ASD vs. non-ASD mini-brains. A closer look at cell growth showed that inhibitory neurons, responsible for keeping nerve signals in check, were increased in number in the ASD mini-brains. Teasing out this discovery further pinpointed a protein, called FOXG1, which was responsible for the increased cell growth of the inhibitory neurons.

Fluorescent microscopy images of minibrain organoids derived from ASD patients (right) and unaffected family members (left). The red and green color indicate the increased presence of inhibitory neurons in the ASD minibrain (right). (Image credit: Mariani et al. Cell Volume 162, Issue 2, p375–390.

Fluorescent microscopy images of minibrain organoids derived from ASD patients (right) and unaffected family members (left). The red and green color indicate the increased presence of inhibitory neurons in the ASD minibrain (right). (Image credit: Mariani et al. Cell Volume 162, Issue 2, p375–390, Fig 4I.)

Here’s the interesting part if you’re still with me: of the four patient samples used in this study, higher levels of FOXG1 protein correlated with more severe ASD. And blocking the production of FOXG1 in the ASD mini-brains reduced the inhibitory neurons back to normal levels. Although this initial finding doesn’t directly link FOXG1 and autism, the results suggest a common disease mechanism: that autism may arise by over producing FOXG1 which in turn creates too many inhibitory neurons during brain development and somehow disrupts connections between neurons.

In an interview with The Scientist, CIRM-funded grantee Alysson Muotri of UCSD, who also studies autism using patient derived iPS cells, finds this possible commonality in ASD remarkable:

“These are patients with idiopathic autism that do not share any genetic causes, and yet the authors find phenotypes shared between their cells. That’s impressive. If someone had asked me, I would have said, ‘You won’t find anything in common, it’s probably going to be a mixed bag.’ But no . . . there seems to be key things that are dysregulated in all of them.”

Stem cell stories that caught our eye: fixing defects we got from mom, lung repair and staunching chronic nerve pain

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.

Two ways to clean up mitochondrial defects. Every student gets it drilled into them that we get half our genes from mom and half from dad, but that is not quite right. Mom’s egg contains a few genes outside the nucleus in the so-called powerhouse of the cell, the mitochondria that we inherit only from mom. The 13 little genes in that tiny organelle that are responsible for energy use can wreak havoc when they are mutated. Now, a multi-center team working in Oregon and California has developed two different ways to create stem cells that match the DNA of specific patients in everyway except those defective mitochondrial genes.

The various mitochondrial mutations tend to impact one body system more than others. The end goal for the current research is to turn those stem cells into healthy tissue that can be transplanted into the area most impacted by the disease in a specific patient. That remains some years away, but this is a huge step in providing therapies for this group of diseases.

Currently, we have two ways of making stem cells that match the DNA of a patient, which hopefully result in transplantable cells that can avoid immune rejection. One is to reprogram adult tissue into induced pluripotent (iPS type) stem cells and the other uses the techniques called Somatic Cell Nuclear Transfer (SCNT), often called therapeutic cloning. The current research did both.

The team converted the SCNT stem cells into various needed tissues such as these nerve precursor cells.

The team converted the SCNT stem cells into various needed tissues such as these nerve precursor cells.

The iPS work relied on the fact that our tissues are mosaics because of the way mitochondria get passed on when cells divide. So not all cells show mitochondrial mutations in people with “mito disease” —how impacted families tend to refer to it, as I found out through a distant cousin with a child valiantly struggling with one form of the disease. Because each iPS stem cell line arises from one cell, the researchers could do DNA analysis on each cell line and sort for ones with few or no mutations, resulting in healthy stem cells, which could become healthy transplant tissue.

But for some patients, there are just too many mutations. For those the researchers inserted the DNA from the patient into a healthy donor egg containing healthy mitochondria using SCNT. The result: again healthy stem cells.

“To families with a loved one born with a mitochondrial disease waiting for a cure, today we can say that a cure is on the horizon,” explained co-senior author Shoukhrat Mitalipov at the Oregon Stem Cell Center in a story in Genetic Engineering News. “This critical first step toward treating these diseases using gene therapy will put us on the path to curing them and unlike unmatched tissue or organ donations, combined gene and cell therapy will allow us to create the patients’ own healthy tissue that will not be rejected by their bodies.”

ScienceDaily ran the Oregon press release, HealthCanal ran the press release from the Salk Institute in La Jolla home of the other co-senior author Juan Carlos Izpisua Belmonte, whose lab CIRM funds for other projects. And Reuters predictably did a piece with a bit more focus on the controversy around cloning. Nature published the research paper on Wednesday.

Stem cells to heal damaged lungs. Lung doctors dealing with emphysema, cystic fibrosis and other lung damage may soon take a page from the playbook of cancer doctors who transplant bone marrow stem cells. A team at Israel’s Weizmann Institute has tested a similar procedure in mice with damaged lungs and saw improved lung function

Transplanted lung cells continued to grow at six weeks (left) and 16 weeks (right).

Transplanted lung cells continued to grow at six weeks (left) and 16 weeks (right).

Stem cells are homebodies. They tend to hang out in their own special compartments we call the stem cell niche, and if infused elsewhere in the body will return home to the niche. Bone marrow transplants make use of that tendency in two ways. Doctors wipe out the stem cells in the niche so that there is room there when stem cells previously harvested from the patient or donor cells are infused after therapy.

The Weizmann team did this in the lungs by developing a method to clear out the lung stem cell niche and isolating a source of stem cells capable of generating new lung tissue that could be infused. They now need to perfect both parts of the procedure. ScienceDaily ran the institute’s press release.

Stem cells for chronic pain due to nerve damage. Neuropathy, damaged nerves caused by diabetes, chemotherapy or injury tends to cause pain that resists treatment. A team at Duke University in North Carolina has shown that while a routine pain pill might provide relief for a few hours, a single injection of stem cells provided relief for four to five weeks—in mice.

They used a type of stem cell found in bone marrow known to have anti-inflammatory properties called Bone Marrow Stromal Cells (BMSCs). They infused the cells directly into the spinal cavity in mice that had induced nerve damage. They found that one chemical released by the stem cells, TGF Beta1, was present in the spinal fluid of the treated animals at higher than normal levels. This finding becomes a target for further research to engineer the BMSCs so that they might be even better at relieving pain. ScienceNewsline picked up the Duke press release about the research published in the Journal of Clinical Investigation.

Giving stem cells the right physical cues produced micro hearts, maybe a tool to avoid birth defects

Heart defects, one of the leading types of birth defects, often result from drugs mom is taking, but we have not had a good model of developing fetal hearts to test drugs for these side effects. Now, a team at the University of California, Berkeley and the Gladstone Institutes has created micro heart chambers in a lab dish by providing the starting stem cells with the right physical cues. And they found these mini-hearts can predict birth defects.

Different types of cells required to make functioning heart tissue show up as different colors here.

Different types of cells required to make functioning heart tissue show up as different colors here.

As we have written before, it takes a neighborhood to raise a stem cell into a wanted adult cell. While most lab cultures maturing stem cells into adult tissue are flat, the developing fetal heart grows in an environment with many physical cues, both chemical and pressure. The Berkeley team added a chemical layer to the cell culture dish and etched it to provide added physical cues. The result produced both connective tissue and heart muscle that were organized into micro heart chambers that could beat.

“We believe it is the first example illustrating the process of a developing human heart chamber in vitro,” said Kevin Healy, co-senior author of the study at UC Berkeley. “This technology could help us quickly screen for drugs likely to generate cardiac birth defects, and guide decisions about which drugs are dangerous during pregnancy.”

The team took the added step of testing a drug known to cause birth defects, thalidomide. When the stem cells were growing with the drug added to the culture, they did not develop into the same micro chambers.

The Berkeley bioengineers started with stem cells reprogrammed from adult skin tissue in the CIRM-funded lab of Bruce Conklin at the Gladstone, the other co-senior author on the paper. These iPS-type stem cells were essential to the project.

“The fact that we used patient-derived human pluripotent stem cells in our work represents a sea change in the field,” said Healy. “Previous studies of cardiac micro-tissues primarily used harvested rat cardiomyocytes, which is an imperfect model for human disease.”

 

Berkeley issued a press release on the work and Popular Science wrote a piece on it complete with a fun embedded video of the beating tissue. The journal Nature Communication ran the original research publication today.

Stem cell stories that caught our eye: correcting cystic fibrosis gene, improving IVF outcome, growing bone and Dolly

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.

Cystic Fibrosis gene corrected in stem cells. A team at the University of Texas Medical School at Houston corrected the defective gene that causes cystic fibrosis in stem cells made from the skin of cystic fibrosis patients. In the long term the advance could make it possible to grow new lungs for patients with genes that match their own—with one life-saving exception—and therefore avoid immune rejection. But, the short-term outcome will be a model for the disease that provides tools for evaluating potential new drug therapies.

“We’ve created stem cells corrected for the cystic fibrosis mutation that potentially could be utilized therapeutically for patients,” said Brian Davis the study’s senior author in a university press release. “While much work remains, it is possible that these cells could one day be used as a form of cell therapy.”

The researchers made the genetic correction in the stem cells using the molecular scissors known as zing finger nucleases. Essentially they cut out the bad gene and pasted in the correct version.

Stem cell researchers boost IVF. Given all the ethical issues raised in the early years of embryonic stem cell research it is nice to be able to report on work in the field that can boost the chances of creating a new life through in vitro fertilization (IVF). Building on earlier work at Stanford a CIRM-funded team there has developed a way to detect chromosome abnormalities in the embryo within 30 hours of fertilization.

Chromosomal abnormalities account for a high percent of the 60 to 70 percent of implanted embryos that end up in miscarriage. But traditional methods can’t detect those chromosomal errors until day five or six and clinicians have found that embryos implant best three to four days post fertilization. This new technique should allow doctors to implant only the embryos most likely to survive.

“A failed IVF attempt takes an emotional toll on a woman who is anticipating a pregnancy as well as a financial toll on families, with a single IVF treatment costing thousands and thousands of dollars per cycle. Our findings also bring hope to couples who are struggling to start a family and wish to avoid the selection and transfer of embryos with unknown or poor potential for implantation,” explained Shawn Chavez who led the team and has since moved to Oregon Health Sciences University.

The study, which used recent advanced technology in non-invasive imaging, was described in a press release from Oregon.

Fun TED-Ed video shows how to grow bone. Medical Daily published a story this week about a team that had released a TED-Ed video earlier this month on how to grow a replacement bone on the lab. The embedded video provides a great primer on how we normally grow and repair bone in our bodies and how that knowledge can inform efforts to grow bone in the lab.

In particular, the story walks through a scenario of a patient with a bone defect too large for our normal repair mechanisms to patch up. It describes how scientist can take stem cells from fat, use 3D printers to mold a scaffold the exact shape of the defect, and culture the stem cells on the scaffold in the lab to create the needed bone.

The video and story reflect the work of New York-based company EpiBone and its tissue engineer CEO Nina Tandon.

Happy birthday Dolly (the sheep). July 5 marked the 19th anniversary of the first cloned mammal, Dolly the sheep in Scotland. For fans of the history of science, MotherBoard gives a good brief history of the resulting kerfuffle and a reminder that Dolly was not very healthy and the procedure was not and is not ready to produce cloned human.

Dolly's taxidermied remains are in a museum in Scotland. She died after only six years, about half the normal life expectancy.

Dolly’s taxidermied remains are in a museum in Scotland. She died after only six years, about half the normal life expectancy.

Parkinson’s blog explains the science behind turning skin cells into a model for the disease

When my colleagues and I write about new advances in stem cell science we often rely on what I refer to as the Sydney Harris method of explaining the science. One of the cartoonist’s most reproduced drawings shows a researcher writing a series of steps on a chalk board with one in the middle being “then a miracle happens.”

Alex was diagnosed with Parkinson's at age 36. His skin cells became a model for the disease.

Alex was diagnosed with Parkinson’s at age 36. His skin cells became a model for the disease.

Our goal usually centers on helping our readers understand an advance and how it moves the field forward, not describing how the scientist actually knows what he or she is reporting. For anyone who wants to get inside the science, particularly about reprogramming skin cells to be stem cells, which we write about often, I suggest a visit to “Alex’s Skin Cell Blog.” A patient with young-onset Parkinson’s disease, it chronicles turning Alex’s skin cells into a model for the disease.

The research takes place at the Parkinson’s Institute in Sunnyvale and the blog features a conversation between Alex and researchers there. Most of the columns feature a CIRM-funded graduate student Lauren Pijanowski, and more recently, Birgitt Schuele.

They explain in pretty understandable pros and illustrations how scientists know things like: were they successful in getting the skin cells to become stem cells; how they make sure the reprogramming process does not damage the cells; and how they keep Alex’s cells alive in a tissue bank. In the most recent, Birgitt explains the use of fluorescent markers to identify cells that have become true stem cells.

This resource could be extremely valuable to teachers, but can also be fun for the simply science curious. For a wealth of more basics on stem cells for teachers, students or the science curious, also check out our high school curriculum.

Not all reprogrammed stem cells are the same—an eye-catching example

Scientists can take any adult tissue whether skin, blood or nerve and use genetic factors to reprogram them into embryonic-like stem cells. But the Nobel Prize-winning technique does not produce stem cells with equal ability to mature into various tissues needed to repair damage from disease or injury.

A team at St. Jude Children’s Research Hospital recently showed that stem cells made from a type of nerve in the eye produced retinal cells more efficiently than stem cells made from skin. The finding fits well with a few years of evidence that reprogrammed stem cells, called iPSCs (induced pluripotent stem cells), retain some memory of what they were before they were reprogrammed into stem cells.

Retinal cells grown from stem cells.

Retinal cells grown from stem cells.

The research, published in Cell Stem Cell, took the extra step to identify one factor that allowed the eye nerve cells to remember their origin. Adult cells develop changes in the structure around the genes called epigenetic markers. Those markers help regulate whether the genes are turned on or off. The St. Jude’s team found one specific epigenetic switch that contributed to the nerve-derived stem cells’ memory.

They used a new technique they developed called STEM-RET that let them quantify how good various stem cells are at creating retinal cells. Then they looked for epigenetic fingerprints to use as markers for isolating those cells. Michael Dyer, who led the team, explained the value of finding and sorting stem cells with particular traits in a press release picked up by ScienceNewsline:

 

“Such fingerprints would tell researchers which stem cell lines would most likely be effective in making retinal cells, bone marrow cells or other types of mature cells for therapeutic purposes.”

The team also used a 3-D culture technique that seemed more efficient than standard cell cultures. Considering that many current processes for making a desired cell type for transplant are not sufficiently efficient for broad therapeutic use, these types of practical advances could be exactly what the field needs to reach mainstream clinical care.

CIRM funds several projects looking to treat blindness caused by retinal disease.