Testing a drug is safe before you give it to a pregnant woman

Pregnant woman holding medicine.

When a doctor gives you a medication you like to think that it’s safe, that it has been tested to make sure it will do you some good or, at the very least, won’t do you any harm. That’s particularly true when the patient is a pregnant woman. You hope the medication won’t harm her or her unborn child. Now scientists in Switzerland have found a new way to do that that is faster and easier than previous methods, and it uses cell cultures instead of animals.

Right now, drugs that are intended for use in pregnant women have to undergo some pretty rigorous testing before they are approved. This involves lots of tests in the lab, and then in animals such as rats and rabbits. It’s time consuming, costly, and not always accurate because animals never quite mimic what happens in people.

In the past researchers tested new medications in the lab on so-called “embryoid bodies”. These are three-dimensional clumps of cells developed from embryonic stem cells from mice. The problem is that even when tested in this way the cells don’t always reflect what happens to a medication as it passes through the body. For example, some medications can seem fine on the surface but after they pass through the liver can take on toxic qualities. 

So, scientists at ETH Zurich in Basel, Switzerland, developed a better way to test for toxicity.

They took a cell-culture chip and created several compartments on it, in some they placed the embryoid bodies and in others they put microtissue samples from human livers.  The different compartments were connected so that fluid flowed freely from the embryoid bodies to the liver and vice versa.

In a news release, Julia Boos, a lead author of the study, says this better reflects what happens to a medication exposed to a human metabolism.

“We’re the first to directly combine liver and embryonic cells in a body-on-a-chip approach. Metabolites created by the liver cells – including metabolites that are stable for just a few minutes – can thus act directly on the embryonic cells. In contrast to tests on mice, in our test, the substances are metabolised by human liver cells – in other words, just as they would be in the human body when the medication is administered.”

To see if this worked in practice the researchers tested their approach on the chemotherapy drug cyclophosphamide, which is turned into a toxic substance after passing through the liver.

They compared results from testing cyclophosphamide with the new liver/embryoid body method to the older method. They found the new approach was far more sensitive and determined that a 400 percent lower concentration of cyclophosphamide was enough to pose a toxic threat.

The team now hope to refine the test even further so it can one day, hopefully, be applied to drug development on a large scale.

Their findings are published in the journal Advanced Science

Stem cell roundup: summer scientists, fat-blocking cells & recent human evolution

Stem cell photo of the week: high schooler becoming a stem cell pro this summer

InstagramAnnaJSPARK

High school student Anna Guzman learning important lab skills at UC Davis

This summer’s CIRM SPARK Programs, stem cell research internships for high school students, are in full swing. Along with research assignments in top-notch stem cell labs, we’ve asked the students to chronicle their internship experiences through Instagram. And today’s stem cell photo of the week is one of those student-submitted posts. The smiling intern in this photo set is Anna Guzman, a rising junior from Sheldon High School who is in the UC Davis SPARK Program. In her post, she describes the lab procedure she is doing:

“The last step in our process to harvest stem cells from a sample of umbilical cord blood! We used a magnet to isolate the CD34 marked stem cells [blood stem cells] from the rest of the solution.”

Only a few days in and Anna already looks like a pro! It’s important lab skills like this one that could land Anna a future job in the stem cell field. Check out #cirmsparklab on Instagram to view the ever-growing number of posts.

Swiss team identifies a cell type that block formation of fat cells

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(Left) Mature human fat cells grown in a Petri dish (green, lipid droplets). (Right) A section of mouse fat tissue showing, in the middle, a blood vessel (red circle) surrounded by fat cell blocking cells called Aregs (arrows). [Bart Deplancke/EPFL]

Liposuction surgery helps slim and reshape areas of a person’s body through the removal of excess fat tissue. While the patient is certainly happy to get rid of those extra pounds, that waste product is sought after by researchers because it’s a rich source of regenerative cells including fat stem cells.

The exact populations of cells in this liposuction tissue has been unclear, so a collaboration of Swiss researchers – at Ecole Polytechnique Fédérale de Lausanne (EPFL) and Eidgenössische Technische Hochschule Zürich (ETHZ) – used a cutting-edge technique allowing them to examine the gene activity within single cells.

The analysis was successful in identifying several newly defined subpopulations of cells in the fat tissue. To their surprise, one of those cell types did not specialize into fat cells but instead did the opposite: they inhibited other fat stem cells from giving rise to fat cells. The initial experiments were carried out in mice, but the team went on to show similar fat-blocking cells in human tissue. Further experiments will explore the tantalizing prospect of applying these cells to control obesity and the many diseases, like diabetes, that result from it.

The study was published June 20st in Nature.

Connection identified between recent human evolution & risk for premature birth
Evidence of recent evolution in a human gene that’s critical for maintaining pregnancy may help explain why some populations have a higher risk for giving birth prematurely than others. That’s according to a recent report by researchers at the University of Stanford School of Medicine.

The study, funded in part by CIRM’s Genomics Initiative, compared DNA from people with East Asian, European and African ancestry. They specifically examined the gene encoding the progesterone hormone receptor which helps keep a pregnant woman from going into labor too soon. The gene is also associated with preterm births, the leading cause of infant death in the U.S.

The team was very surprise to find that people with East Asian ancestry had an evolutionarily new version of the gene while the European and African populations had mixtures of new and ancient versions. These differences may explain why the risk for premature birth among East Asian populations is lower than among pregnant women of European and African descent, though environment clearly plays a role as well.

Pediatrics professor Gary Shaw, PhD, one of the team leaders, put the results in perspective:

“Preterm birth has probably been with us since the origin of the human species,” said Shaw in a press release, “and being able to track its evolutionary history in a way that sheds new light on current discoveries about prematurity is really exciting.”

The study was published June 21st in The American Journal of Human Genetics.

Stem cell stories that caught our eye: menstrual cycle on a chip, iPS cells from urine, Alpha Stem Cell Clinic Symposium videos

Say hello to EVATAR, a mini female reproductive system on a 3D chip. (Karen Ring)
I was listening to the radio this week in my car and caught snippets of a conversation that mentioned the word “Evatar”. Having tuned in halfway through the story, naturally I thought that the reporters were talking about James Cameron’s sequel to Avatar, and was slightly puzzled about the early press since the sequel isn’t expected to come out until 2020.

I was wrong in my assumption, but not that far off. It turns out that they were actually talking about a cutting edge new technology that generates artificial organs on 3D microfluidic chips. In the case of EVATAR, scientists have developed a functioning mini female reproductive system with all the essential components to recreate the female menstrual cycle. This sounds like science fiction, but it’s real. If you don’t believe me, you can read the publication in the journal Nature Communications.

EVATAR is a 3D organ-on-a-chip representing the female reproductive system. (Photo credit: Woodruff Lab, Northwestern University.)

 The chip consists of small boxes that each house an essential component of the reproductive system including the uterus, fallopian tubes, ovaries, cervix, and vagina. These tissues are generated from human stem cells except for the ovaries which were derived from mouse stem cells. The mini organs are connected to each other by tiny tubes and pumps that simulate blood flow and create a complete reproductive system. By adding specific hormones to this chip, the scientists stimulated the ovaries to produce the hormones estrogen and progesterone and even release an egg.

With EVATAR up and running, scientists are planning to use these personalized devices for various medical purposes including understanding reproductive diseases like endometriosis and testing how drugs affect specific people. The team is also developing a male version of this 3D reproductive chip called ADATAR and plans to study the two models side by side to understand differences in drug metabolism between men and women.

EVATAR is part of a larger project spearheaded by the National Institutes of Health to develop a “body-on-a-chip”. The lead author on the study, Teresa Woodruff from Northwestern University, explained in a news release how scaling down a human body to the size of a small chip that fits in your hand scales up the impact that the technology can have on developing personalized medicine for patients with various diseases.

“If I had your stem cells and created a heart, liver, lung and an ovary, I could test 10 different drugs at 10 different doses on you and say, ‘Here’s the drug that will help your Alzheimer’s or Parkinson’s or diabetes. It’s the ultimate personalized medicine, a model of your body for testing drugs.”

EVATAR has been popular in the press and was picked up by news outlets like NPR, STAT news and Tech Times. You can learn more about this technology by watching the video below provided by Northwestern Medicine.

Abracadabra: Researchers make stem cells from urine (Todd Dubnicoff)
I think one of the reasons the induced pluripotent stem cell (iPSC) technique became a Nobel Prize winning breakthrough, is due to its simplicity. All it takes is a slightly invasive skin biopsy and the addition of a few key factors to reprogram the skin cells into an embryonic stem cell-like state. The method is a game-changer for studying brain development disorders like Down Syndrome. Brain cells from affected individuals are not accessible so deriving these cells from iPSCs is critical in examining the differences between a healthy and Down Syndrome brain.

But skin biopsies are not “slightly invasive” when working with adults or children with an intellectual disability like Down Syndrome. The oversight committees that evaluate the ethics of a proposed human research study often denied such procedures. And even when they are approved, patients or caregivers have often dropped out of studies due to the biopsy method. This sensitive situation has hampered the progress of iPSC-based studies of Down Syndrome.

This week, a research team at Case Western Reserve University School of Medicine reported in STEM CELLS Translational Medicine that they’ve overcome this obstacle with a truly non-invasive procedure: collect cells via urine samples. But wait there’s more. It turns out that iPSCs derived from urine are more stable than their skin biopsy counterparts. The team believes it’s because skin cells, unlike cells found in urine, are exposed to the sunlight’s DNA-damaging UV radiation.

So far the team has banked iPSC lines from ten individuals with Down Syndrome which they will share with other researchers. Team lead Alberto Costa described the importance of these cell lines in a press release:

“Our methods represent a significant improvement in iPSC technology, and should be an important step toward the development of human cell-based platforms that can be used to test new medications designed to improve the quality of life of people with Down syndrome.”

ICYMI the CIRM Alpha Stem Cell Clinic Symposium Talks are Now on YouTube!
Last week, City of Hope hosted a fantastic meeting featuring the efforts of our CIRM Alpha Stem Cell Clinics. It was the second annual symposium and it featured talks from scientists, doctors, patients and advocates about the advancements in stem cell-based clinical trials and the impacts those trials have had on the lives of patients.

We wrote about the symposium earlier this week, but we couldn’t capture all the amazing talks and stories that were shared throughout the day. Luckily, the City of Hope filmed all the talks and they are now available on YouTube. Below are a few that we selected, but be sure to check out the rest on the City of Hope YouTube page.


CIRM President and CEO Randy Mills highlights the goals of the CIRM Alpha Clinics Network and what’s been achieved since its inception in 2014. 


CIRM’s Geoffrey Lomax talks about how the vision of the Alpha Clinics has turned into a reality for patients.

CIRM-funded UC Irvine Scientist, Henry Klassen, talks about his promising stem cell clinical trial for patients with a blinding disease called Retinitis Pigmentosa.

Embryos with abnormal chromosomes can repair themselves

CVS

In a chorionic villus sampling (CVS) test, cells from the fetal side of the placenta are collected and tests for genetic defects.
Image credit: ADAM Health Solutions

Like an increasing number of women, Magdalena Zernicka-Goetz waited later in life to have kids and was pregnant at 44 with her second child. Because older moms have an increased risk of giving birth to children with genetic disorders, Zernicka-Goetz opted to have an early genetic screening test about 12 weeks into her pregnancy. The test, which looks for irregular amounts of chromosomes in the cells taken from the placenta, showed that a quarter of the cells in the developing fetus had genetic abnormalities.

Expectant mothers and tough choices

If she carried the child to term, would the baby have a birth defect? Zernicka-Goetz learned from geneticists that this question was difficult to answer due to a lack of data about what happens to abnormal cells in the developing fetus. Fortunately, her baby was born happy and healthy. But the experience motivated her to seek out a better understanding for the sake of other women who would be faced with similar difficult decisions based on screening tests.

As a professor of developmental biology at Cambridge University, Zernicka-Geotz had the expertise to follow through on this challenge. And in a Nature Communications journal article published yesterday, she and her team report a fascinating result: the very early embryo has the ability to essentially repair itself by getting rid of abnormal cells.

Aneuploidy: You Have the Wrong Number

aneuploidy

Aneuploidy in the developing fetus can lead to genetic disorders. Image credit: Deluca Lab Colorado State University

To reach this finding, the team first had to recreate chromosomal abnormalities in mouse embryos. If you remember your high school or college biology, you’ll recall that before a cell divides, it duplicates each chromosome and then each resulting “daughter” cell grabs one chromosome copy using a retracting spindle fiber structure. The scientists took advantage of the fact that treating dividing cells with the drug reversine destabilizes the spindle fibers and in turn causes an unequal divvying up of the chromosomes between the daughter cells. In scientific jargon the condition is called aneuploidy.

Rescuing the embryo by cellular suicide

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Generating early mouse embryos with an equal mix of normal cells and cells with abnormal chromosome numbers (induced via reversine treatment). Image credit: Bolton et al. Nat Commun. 2016 Mar 29;7:11165

The researchers created mosaic embryos at the eight cell stage in which half the cells had a normal set of chromosomes while the other half we’re the reversine-treated cells with abnormal numbers of chromosomes. With these genetically mosaic embryos, the team tagged the cells with fluorescent dye and used time-lapsed imaging to track the fate of each cell for 48 hours. They found a decrease specifically in the portion of cells that stemmed from the abnormal cells.

A follow up experiment examined cell death as a way to help explain the reduced number of abnormal cells. The researchers found that compared to the normal set of cells in the embryo, the abnormal cells had a significantly higher evidence of apoptosis, or programmed cell death, a natural process that occurs to eliminate harmful or damaged cells. According to Zernicka-Geota and the team, this is the first study to directly show the elimination of abnormal cells in the growing embryo.

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Time lapse images showing an abnormal cell (green cell indicated by arrow) being eliminated by apoptosis (programmed cell death) and then engulfed by normal (red) cells (engulfment indicated by star).
Image credit: Bolton et al. Nat Commun. 2016 Mar 29;7:11165

To look at their fate beyond the very early stages of development, the mosaic mouse embryos were implanted into foster mothers and allowed to develop to full term. Thirteen of the twenty-six embryos transferred to foster mothers gave rise to live pups which were all healthy after four months of age.

As Zermicka-Geota stated in a university press release picked up by Medical Express, if these findings reflect what goes on in human development, then decisions based on genetic screening results may not be clear cut:

“We found that even when half of the cells in the early stage embryo are abnormal, the embryo can fully repair itself. It will mean that even when early indications suggest a child might have a birth defect because there are some, but importantly not all abnormal cells in its embryonic body, this isn’t necessarily the case.”

Implications for genetic testing on days-old IVF embryos

These new results don’t suggest that current genetic testing is obsolete. For instance, the amniocentesis test, which collects fetal tissue from the mother’s amniotic fluid between 14 and 20 weeks of pregnancy, can detect genetic disorders with 98-99% accuracy. But this study may have important implications for testing done much earlier. When couples conceive via in vitro fertilization, a so-called pre-implantation genetic diagnosis (PGD) test can be performed on embryos that are only a few days old. In the test, a single cell is removed – without damaging the embryo – and the cell is tested for chromosomal defects. Based on this study, a positive PGD test may be misleading if that abnormal cell was destined to be eliminated from the embryo.

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.

Stem cell stories that caught our eye: a new type of stem cell, stomach cancer and babies—stem cell assisted and gene altered

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.

New type of stem cell easier to grow, more versatile. Both the professional scientific media and the lay science media devoted considerable ink and electrons this week to the announcement of a new type of stem cell—and not just any stem cell, a pluripotent one, so it is capable of making all our tissues. On first blush it appears to be easier to grow in the lab, possibly safer to use clinically, and potentially able to generate whole replacement organs.

The newly found stem cells (shown in green) integrating into a mouse embryo.

The newly found stem cells (shown in green) integrating into a mouse embryo.

How a team at the Salk Institute made the discovery was perhaps best described in the institute’s press release picked up by HealthCanal. They sought to isolate stem cells from a developing embryo after the embryo had started to organize itself spatially into compartments that would later become different parts of the body. By doing this they found a type of stem cell that was on the cusp of maturing into specific tissue, but was still pluripotent. Using various genetic markers they verified that these new cells are indeed different from embryonic stem cells isolated at a particular time in development.

The Scientist did the best job of explaining why these cells might be better for research and why they might be safer clinically. They used outside experts, including Harvard stem cell guru George Daly and CIRM-grantee from the University of California, Davis, Paul Knoepfler, to explain why. Paul described the cells this way:

“[They] fit nicely into a broader concept that there are going to be ‘intermediate state’ stem cells that don’t fit so easily into binary, black-and-white ways of classifying [pluripotent cells].”

The Verge did the best job of describing the most far-reaching potential of the new cells. Unlike earlier types of human pluripotent cells, these human stem cells, when transplanted into a mouse embryo could differentiate into all three layers of tissue that give rise to the developing embryo. This ability to perform the full pluripotent repertoire in another species—creating so called chimeras—raises the possibility of growing full human replacement organs in animals, such as pigs. The publication quotes CIRM science officer Uta Grieshammer explaining the history of the work in the field that lead up to this latest finding.

Stem cells boost success in in vitro fertilization.  Veteran stem cell reporter and book author Alice Park wrote about a breakthrough in Time this week that could make it much easier for older women to become pregnant using in vitro fertilization. The new technique uses the premise that one reason older women’s eggs seem less likely to produce a viable embryo is they are tired—the mitochondria, the tiny organs that provide power to cells, just don’t have it in them to get the job done.

The first baby was born with the assistance of the new procedure in Canada last month. The process takes a small sample of the mother-to-be’s ovarian tissue, isolates egg stem cells from it, extracts the mitochondria from those immature cells and then injects them into the woman’s mature, but tired eggs. Park reports that eight women are currently pregnant using the technique. She quotes the president of the American Society of Reproductive Medicine on the potential of the procedure:

“We could be on the cusp of something incredibly important. Something that is really going to pan out to be revolutionary.”

But being the good reporter that she is, Park also quotes experts that note no one has done comparison studies to see if the process really is more successful than other techniques.

Why bug linked to ulcers may cause cancer. The discovery of the link between the bacteria H. pylori and stomach ulcers is one of my favorite tales of the scientific process. When Australian scientists Barry Marshall and Robin Warren first proposed the link in the early 1980s no one believed them. It took Marshall intentionally swallowing a batch of the bacteria, getting ulcers, treating the infection, and the ulcers resolving, before the skeptics let up. They went on to win the Nobel Prize in 1995 and an entire subsequent generation of surgeons no longer learned a standard procedure used for decades to repair stomach ulcers.

In the decades since, research has produced hints that undiagnosed H. pylori infection may also be linked to stomach cancer, but no one knew why. Now, a team at Stanford has fingered a likely path from bacteria to cancer. It turns out the bacteria interacts directly with stomach stem cells, causing them to divide more rapidly than normal.

They found this latest link through another interesting turn of scientific process. They did not feel like they could ethically take samples from healthy individuals’ stomachs, so they used tissue discarded after gastric bypass surgeries performed to treat obesity. In those samples they found that H. pylori clustered at the bottom of tiny glands where stomach stem cells reside. In samples positive for the bacteria, the stem cells were activated and dividing abnormally. HealthCanal picked up the university’s press release on the work.

Rational balanced discussion on gene-edited babies.   Wired produced the most thoughtful piece I have read on the controversy over creating gene-edited babies since the ruckus erupted April 18 when a group of Chinese scientists published a report that they had edited the genes of human eggs. Nick Stockton wrote about the diversity of opinion in the scientific community, but most importantly, about the fact this is not imminent. A lot of lab work lies between now and the ability to create designer babies. Here is one particular well-written caveat:

“Figuring out the efficacy and safety of embryonic gene editing means years and years of research. Boring research. Lab-coated shoulders hunched over petri dishes full of zebrafish DNA. Graduate students staring at chromatographs until their eyes ache.”

He discusses the fears of genetic errors and the opportunity to layer today’s existing inequality with a topping of genetic elitism. But he also discusses the potential to cure horrible genetic diseases and the possibility that all those strained graduate student eyes might bring down the cost to where the genetic fixes might be available to everyone, not just the well heeled.

The piece is worth the read. As he says in his closing paragraph, “be afraid, be hopeful, and above all be educated.”

What everybody needs to know about CIRM: where has the money gone

It’s been almost ten years since the voters of California created the Stem Cell Agency when they overwhelmingly approved Proposition 71, providing us $3 billion to help fund stem cell research.

In the last ten years we have made great progress – we will have ten projects that we are funding in or approved to begin clinical trials by the end of this year, a really quite remarkable achievement – but clearly we still have a long way to go. However, it’s appropriate as we approach our tenth anniversary to take a look at how we have spent the money, and how much we have left.

Of the $3 billion Prop 71 generates around $2.75 billion was set aside to be awarded to research, build laboratories etc. The rest was earmarked for things such as staff and administration to help oversee the funding and awards.

Of the research pool here’s how the numbers break down so far:

  • $1.9B awarded
  • $1.4B spent
  • $873M not awarded

So what’s the difference between awarded and spent? Well, unlike some funding agencies when we make an award we don’t hand the researcher all the cash at once and say “let us know what you find.” Instead we set a series of targets or milestones that they have to reach and they only get the next installment of the award as they meet each milestone. The idea is to fund research that is on track to meet its goals. If it stops meetings its goals, we stop funding it.

Right now our Board has awarded $1.9B to different institutions, companies and researchers but only $1.4B of that has gone out. And of the remainder we estimate that we will get around $100M back either from cost savings as the projects progress or from programs that are cancelled because they failed to meet their goals.

So we have approximately $1B for our Board to award to new research, which means at our current rate of spending we’ll have enough money to be able to continue funding new projects until around 2020. Because these are multi-year projects we will continue funding them till around 2023 when those projects end and, theoretically at least, we run out of money.

But we are already working hard to try and ensure that the well doesn’t run dry, and that we are able to develop other sources of funding so we can continue to support this work. Without us many of these projects are at risk of dying. Having worked so hard to get these projects to the point where they are ready to move out of the laboratory and into clinical trials in people we don’t want to see them fall by the wayside for lack of support.

Of the $1.9B we have awarded, that has gone to 668 awards spread out over five different categories:

CIRM spending Oct 2014

Increasingly our focus is on moving projects out of the lab and into people, and in those categories – called ‘translational’ and ‘clinical’ – we have awarded almost $630M in funding for more than 80 active programs.

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Under our new CIRM 2.0 plan we hope to speed up the number of projects moving into clinical trials. You can read more about how we plan on doing there in this blog.

It took Jonas Salk almost 15 years to develop a vaccine for polio but those years of hard work ended up saving millions of lives. We are working hard to try and achieve similar results on dozens of different fronts, with dozens of different diseases. That’s why, in the words of our President & CEO Randy Mills, we come to work every day as if lives depend on us, because lives depend on us.

New Videos: Downton Abbey, preeclampsia, and the search for a cure using stem cells

(Downton Abbey Spoiler Alert: skip ahead to the video if you haven’t seen Season 3!)

If you’re one of the estimated 10 million devoted Downton Abbey TV viewers, then you most probably have heard of the word “preeclampsia.” In a heart-wrenching episode from season 3 of the early 20th century British drama, one of the characters dies while giving birth due to the complications of preeclampsia.

A fan myself, I too watched in shock as the plot unfolded. But I was at least comforted by the thought that surely this disease no longer has tragic outcomes today in the early 21st century. Boy was I wrong. As CIRM-grantee Mana Parast pointed out during her Spotlight on Disease presentation to the CIRM Governing Board two weeks ago (now viewable on our website), preeclampsia and related disorders are still a widespread problem for expecting mothers:

“They complicate 5-8% of all pregnancies worldwide, and they cause multiple maternal and neonatal complications. So in fact preeclampsia is the leading cause of maternal mortality in the developed world. It’s also the leading cause of fetal growth restriction and there’s no cure … except to deliver the baby. In fact preeclampsia is the number one cause of induced preterm delivery in the U.S.”

Preeclampsia is often called “the Silent Killer” because the symptoms often arise suddenly in the second half of pregnancy. The main noticeable symptoms for the expectant mother are high blood pressure and high protein levels in the urine, or proteinuria. Silvia Michelazzi, a preeclampsia survivor, shared with the Board her daughter’s birth story:

“My pregnancy, I was thinking, was going well. I knew Mia was a little bit smaller than average but that was pretty much it. But at a doctor’s appointment, it was found out that I had high blood pressure and proteinuria and I was rushed to the hospital and the baby was delivered 48 hours later [at 29 weeks] because there’s really nothing else to do but delivery the baby. I can’t tell you how hard it was to see the baby so small. It turned out she weighed 2 pounds 8 ounces.”

Mia, now three, spent two months in the neonatal intensive care unit but is now doing remarkably well. But some babies aren’t so lucky. They can have intestinal problems, bleeding in their brain, retinopathy of prematurity (a condition that can lead to blindness), and the list goes on. Even when they survive the neonatal stage they still have an increased risk of heart disease and diabetes over the course of their lives. And all of these scary, sometimes fatal complications are basically due to, as Dr. Parast puts it, “just having a bad placenta.”

The placenta is a transient organ that only appears during pregnancy and is critical for exchange of food, blood and oxygen between the mother and fetus. Dr. Parast, a perinatal pathologist at UC San Diego, studies the development of the placenta with the ultimate hope of finding treatments for preeclampsia. If you imagine the early embryo as a tiny hollow ball of cells, it’s the outer cells called trophoblasts that ultimately form the placenta while a clump of cells inside the hollow “ball” go on to form the fetus.

Examination of a preeclamptic placenta after delivery shows that preeclampsia is a disease marked by a malfunction in trophoblast maturation leading to abnormal placenta development. The aim of Dr. Parast’s team is to mimic preeclampsia in the lab but it’s been a tricky disease to model because preeclampsia is unique to primates so experiments in mice is not an option. Instead, with the help of CIRM-funding, Parast’s lab is embarking on a project to bank tissue from preeclamptic placentas and derive trophoblasts using the induced pluripotent stem cell (iPS) technique. With these iPS-derived trophoblasts in hand, the team can screen for drugs that restore proper trophoblast maturation and placental development.

And in a strange twist that you usually only see on a TV show – it turns out that Dr. Matteo Moretto-Zito, a researcher in Parast’s lab, is the father of little Mia. Moretto-Zito had joined the lab shortly before his wife Silvia was diagnosed with preclampsia. He also spoke to the Board and had this to say about his unique perspective:

“I consider myself extremely lucky for two reasons: number one, Mia’s story ended up really well so that is great and reason number two, because I am part of a team that can make a difference.”

Here’s to hoping that Matteo and the entire Parast team make a difference and find a treatment to end preeclampsia complications for future moms and babies.