Stem Cell Clinic

Artificial Early Mouse Embryos Created In The Lab Using Stems Cells Rather Than Sperm Or Eggs – IFLScience

A groundbreaking study has seen scientists create the early stages of artificial mice embryos in a lab using stem cells, rather than sperm or eggs, for the first time.

Its still very early days for the research, and it has some big problems to iron out, but itcould potentially pave the way towards creating viable embryos just from cultured cells. It could also provide scientists with an indefinite source of blastocysts to study the early stages of development, without the need for sperm, eggs, or natural embryos.

These studies will help us to better understand the very beginnings of life; how early on in life a single cell can give rise to millions of cells and how they are assembled in space and time to give rise to a fully developed organism. Importantly, this work avoids the use of natural embryos and is scalable, Juan Carlos Izpisua Belmonte, study author and professor in Salks Gene Expression Laboratory, explained in a statement.

Reporting in the journal Cell, researchers at the Salk Institute and the University of Texas Southwestern Medical Center created structures resembling mouse blastocysts, known as blastoids.

Blastocysts are structures made up of 100+ cells or so, found in the very early stages of development in mammals. After the blastocyst implants itself into the uterus, it can develop into an embryo.Typically, the blastocyst forms around five days after a sperm has fertilized an egg.

However, the researchers managed to create an early form of blastocyst using pluripotent stem cells, master cells that can turn into almost any kind of tissue in the body, obtained from adult mouse cells.The stem cells were placed together and nurtured in a special culture medium. They soon formed connections with each other, eventually forming a ball of cells with an inner and outer layer.

The structure of this, according to the researchers, was remarkably like a natural blastocyst. The artificial blastoids contained the same three primordial cell types found in natural blastocysts, along with being a similar size and similar gene expression.

Other researchers working in the field have described the research as wonderful, significant, and outstanding, although they warn there are still many hurdles to overcome before we see this research being applied.

For example, its noteworthy that the blastocyst-like structures showed signs of malformation and disorganization, meaning they wouldnt be able to develop into a fully viable embryo or mouse.

I would caution against interpreting the current study as showing that embryos can be made from adult tissues this has the potential to raise undue ethical concerns, the structures made are not embryos, and the research is in mice not humans, said Dr Harry Leitch, a stem cell biologist at the MRC London Institute of Medical Sciences and Imperial College London who was not involved in the study.

In reality, this study reports incremental findings in a pre-existing model system, and makes a valuable contribution to ongoing research in the field.

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Artificial Early Mouse Embryos Created In The Lab Using Stems Cells Rather Than Sperm Or Eggs - IFLScience

A stop-motion movie of the whole brain, starring new neurons – Spectrum

Cells on the move: A new technique helps reveal patterns in the migration of neurons (green) to their destination (red).

A new method visualizes nascent neurons in the mouse brain and follows them as they migrate to their final destinations.

The method essentially a time series of 3D images may shed light on processes that unfold during brain development.

We take snapshots at different time points, then match them together to see dynamic processes, says Alexander Lazutkin, senior scientist at the P.K. Anokhin Institute of Normal Physiology in Moscow, Russia. Lazutkin presented the work yesterday at the 2019 Society for Neuroscience annual meeting in Chicago, Illinois.

Researchers can use the method to study the birth of neurons and the complex ways in which they migrate through the brain. Abnormalities in these processes have been implicated in autism.

In the weeks after a mouse is born, neural stem cells in its brain continue to divide and generate neurons. Lazutkins team marked these dividing cells throughout the brain by adapting a fluorescent labeling technique typically used on thin sections of tissue. (The labeling method was published 12 September in MethodsX1.)

In the new work, they labeled cells in the brains of adult mice. They used a fluorescent microscope to take a snapshot of the whole brain of one set of animals, and then a different set of animals one day older the next day, and so on. They built an algorithm to stitch the images together and fill in the gaps to form a time series.

The result is a movie that tracks cells locations as they migrate toward their destination. The cells originate in the subventricular zone, one of two places where cells continue to divide in the adult brain. The movie shows the migrating cells reaching the olfactory bulb in about 10 days.

It also shows cells forming a stripe pattern in the subventricular zone.

We suppose these are distinct migration streams, Lazutkin says. You cant see this pattern on a conventional [2D] slide. But when you have the full picture, you can recognize them.

Lazutkin and his colleagues plan to use the method to look at differences in early brain development between typical mice and mouse models of autism particularly those with mutations that lead to altered brain growth.

For more reports from the 2019 Society for Neuroscience annual meeting, please click here.

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A stop-motion movie of the whole brain, starring new neurons - Spectrum

Humans evolved to think faster by slowing down brain development – New Scientist News

By Clare Wilson

D. ROBERTS/SCIENCE PHOTO LIBRARY

How did humans get to be so much cleverer than other apes? One counter-intuitive idea is that it was made possible by a slowdown of our brain growth during fetal development.

The suggestion comes from a relatively new approach of growing embryonic-like stem cells in a dish and coaxing them to turn into nervous system cells until they form pea-sized three-dimensional clumps known as organoids.

These mini brains seem to replicate real neuron behaviour more closely than when brain cells are grown in a flat layer. They have nothing like the complexity needed for thought or consciousness, but do develop into different kinds of brain tissue and display patterns of electrical activity that have some similarities with real brains.

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Human brains are certainly bigger than those of our nearest primate relatives, but there are surprisingly few differences in structure. So it is unclear what gives rise to the huge differences in our mental abilities.

Gray Camp at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues used stem cells from humans, chimpanzees and macaque monkeys to make mini brains for each species. After four months, a key difference was that nerve cells in the chimp and monkey organoids were more mature.

Identifying such differences may be a step towards explaining why humans are more intelligent although the team doesnt speculate on exactly how their findings might relate to this puzzle.

Until now it wasnt possible to compare human and chimp organ development, says Camp. The organoids, some made from stem cells that can be generated directly from adult cells, offer a way of making that comparison.

Camp and his team also delved into another long-standing puzzle: why there are so few differences between the protein-coding genes of humans and the other apes, considering the huge disparity in our intellects.

A recent technique for analysing which genes are turned on or off in individual cells, known as single cell RNA sequencing, has suggested the answer might lie in differences in which genes are turned on at different times.

In the latest study, Camps team charted which genes are turned on in different brain cells over four months of mini brain development, comparing the results across humans, chimps and macaques, to make a database other researchers can also use.

Organoids are most useful for society in letting us understand disease, says Camp. But its also very interesting to think about where our species came from and how we became uniquely human.

Journal reference: Nature, DOI: 10.1038/s41586-019-1654-9

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Healthcare Terms Are Out of Touch, Says Mom Advocate – Medscape

This transcript has been edited for clarity.

Eric J. Topol, MD: Hello. I'm Eric Topol, editor-in-chief for Medscape. I'm thrilled to speak with Hala Durrah today, who I got to know about through a remarkable essay she wrote for Health Affairs back in March. Hala, welcome to our program.

Hala H. Durrah, MTA: Thank you for having me.

Topol: It's a real pleasure and this an important and critical topic. Your essay was "My Child Is Sick; Don't Call Her a 'Consumer.'"[1] There is so much to learn here for Medscape folks. Can you tell us a little bit about your background and your family?

Durrah: Sure. I am a patient/family engagement consultant by profession, which basically means that I work with healthcare organizations and systems around the concept of patient/family engagement, spanning anywhere from patient-centered measurements to quality improvement, and so on. I came to the work, though, not as part of a plan, but by fate and destiny. My firstborn, whose name is Ayah, was born with a very rare liver disease which we knew would require liver transplantation. She is 16 years old now, but as you can imagine, we've been on quite a journey in the healthcare system. In addition, I have four other children and my husband is an adult medical hospitalist at a major academic center on the East Coast, so healthcare is a big piece of our lives.

I realized a few years into the journey with my daughter that I wanted to become more engaged in improving healthcare and partnering with our care teamthe physicians, nurses, pharmacists, and the larger group of specialists that she was seeing on a regular basis. I had the opportunity to volunteer at a local hospital that was looking for more patient/family involvement in some of their quality improvement work, and I decided that this was definitely something I wanted to pursue further, so I did. But my daughter's healthcare journey continues and I continue to see the good, the not so good, and everything in between.

In addition, I think I have a unique perspective because my husband is a physician and works in the hospital setting. I understand and can empathize with the real challenges facing physicians that are constantly placing pressure on them and demanding their time. I am very cognizant of that, so in my work I really try to balance the voice of the patient or caregiver, and the voice of the physician or nurse, because I can definitely see all of the different perspectives. At the end of the day, I think we all really want these meaningful relationships where we communicate and empathize with one another, and at the same time, we all want the best care for each other. That is my goal and the work I've been doing for the past several years.

Topol: That is terrific. You have a panoramic view of the healthcare landscapethat's for sure.

Topol: You wrote about your daughter; it is a miracle story in so many respects. Her name, Ayah, means "sign of God"is that right?

Durrah: Yes. We named her that before I knew she was going to be born with this illness, and it's pretty remarkable that she fit that name and the meaning of her name since she was born. Her first liver transplant, unfortunately, failed within the first 24 hours. As you all know, a liver does not wait, so we were preparing to say goodbye to her when she was about 5 years old.

Subsequently, by miracle, she got another liver 2 days later. It was from the same hospital where she was at, which was even more amazing because her surgeons were prepared to travel anywhere to get another liver. She was placed number one on the nation live listing after that first transplant failed, and it's remarkable that she got another one.

Topol: After she had these two liver transplants at age 5, she got Burkitt lymphoma.

Durrah: Unfortunately, because of her therapies, and also being Epstein-Barr viruspositive, she developed stage III Burkitt lymphoma 2 years after the liver transplant, which was quite devastating, to say the least.

Topol: It required another type of transplant, a bone marrow transplant.

Durrah: Yes. Unfortunately, she had several months of a pretty intense chemotherapy regimen that ultimately failed, and we had to move to an autologous bone marrow transplant. She was not able to have donor cells because she was already an organ transplant recipient. She sat one day in the hospital with a catheter, and they took her stem cells and then gave them back to her about a month later after some more intense chemotherapy.

In all our experiences, I don't believe that physicians and nurses ever defined my daughter as a consumer.

Obviously, she has been through quite a bit. A lot goes along with being a patient of liver disease or a patient who survived cancer with all of the chemotherapy, so while her health is stable, things are constantly moving in the background that we're watching. I tell people that I sometimes look at it like a radar screen. You kind of see the little red dots bleeping and some of them get brighter and some of them get dimmer. A lot of people are monitoring those lights, but I'm the chief monitor of all of those lights and the coordinator of making sure we stay on top of them.

Topol: You are quite an advocate and it is just an amazing story. I want to get into this message that you have about using the term "consumer," because I have hated that term for years. Why do we use this term when we're talking about patients in the health world? You wrote, "I share our story because I am becoming increasingly troubled by a trend in healthcaretoward thinking of patients as 'consumers' but not actually engaging communities in healthcare improvement and innovation." Tell us a bit about this objection of this term, because I think if anybody has a right to object to the use of that term, it would be you.

Durrah: The term definitely does not resonate with me, and I share your strong feelings against the utilization of this term. Overall, I think it continues to underline and push the business imperative of healthcare versus the humanity imperative in which healthcare was initially built upon. I reject in some ways that this notion of consumerism will improve healthcare because healthcare did not start as a business imperative, nor was the framework built to support such a term.

In all of our experiences, I don't believe that physicians and nurses ever defined my daughter as a consumer. I believe [the term] distances us from one another and does not amplify or support that relationship-based care that we all seek to have and to improve. I also don't think "consumer" empowers us, although I understand why some believe it may, because the framework of healthcare is not set up in such a way where "consumer" denotes choice. A lot of healthcare is dictated to the patient or to the caregivers by their insurance companies or their lack thereof, or the communities in which they live, or by lots of different other parties that are involved in it. I'm not quite sure where the choice comes in, especially because no one chooses to be sick. A consumer has choices, but we don't have that choice.

It does not make sense to use that term. I understand where people come from wanting to empower individuals by changing the terminology [to a less] "passive" role of the patient, but I'm not quite sure that changing the terminology we use makes us equals, gives us any more choices, or improves the care we will receive.

Topol: Words are important. This term is hackneyed, it's pervasive, and I think you made the most eloquent case in the history of the medical literature because your intersection with the healthcare world is extensive.

Durrah: Oh my gosh. I'm humbled by that. I'm not sure if I deserve all that, but I appreciate it.

Topol: You have a master's degree from George Washington and you worked in tourism, and you made some interesting parallels between a consumer of tourism versus a patient. Can you talk to us about that?

Durrah: Sure. My master's is in tourism and administration, with a focus in meeting and event management, and here I am in healthcare advocacy now. But I found that it's been very useful because you do see in healthcare this shift of trying to create a tourism-type experience for healthcare. And generally speaking, tourism is a choice; we all choose to travel or to use a certain hotel or rental car company because we've had experiences. Most of the time, you come back from a vacation with great memories, and when you share those memories with others, they may want to have the same experiences as you.

But I don't believe that we can really equate healthcare to a vacation. I'm not quite sure who would utilize that same experience as a vacation. Things that healthcare has that no other industry has are the trauma, pain, and anguish that go into being either a patient or the caregiver of someone. I think physicians and nurses have a lot of emotions in the healthcare experience that you could never find in tourism. And tourism tries to have a constant feedback loop with their customers or consumers; healthcare does not. Yes, we tout these wonderful surveys that are supposed to increase patient satisfaction, but were any of them co-designed with the communities the health systems serve? The answer is no. Do they allow you to really respond in such a way that will provide meaningful data using stories of your experiences in the system? No. So again, trying to equate the healthcare experience with the lessons learned from tourism is a mismatch.

Topol: Right. Even that term "medical tourism" is about a different concept.

There are many parts of your daughter's story that were really touching and deep, but one of the things that stood out was how her liver doctor would hold your hand, and how that was not about consumerism but, as you say, a choice driven by humanity and compassion. This, I think, speaks to the stark dramatic differences between the terms.

Topol: Another term I'm interested in asking you about is "providers." It's another term I don't care for. Should that term be used?

Durrah: It's interesting, because I believe that in the article I do reference "care providers" at one point. Initially when I started in this work, I always [used the specific terms of] "physicians," "nurses," "pharmacists," and so on. All of a sudden that term "provider" got thrown into the mix, and I adapted it because it seemed that everyone was using it to cover all the members of the care team that might interact or touch a patient. I'm guilty of using that term and I got a lot of response after my article came out, particularly from physicians, about how the term "provider" was not liked. I believe the term came about with this whole business imperative/push in healthcare. Insurance companies use that term and healthcare systems have now adopted that term as well, and it probably is in play because of this whole consumerism push as well.

I did prefer saying "physicians" or "nurses" or "pharmacists" and that we're all part of the "care team." I prefer that terminology, just as I prefer to be called a "partner" in my care versus a "consumer" or a "customer." I think that the term does not fit the role that physicians and nurses play. They are not just a provider. I look at them as part of my team and I'm on their team, so we're all working together. I think "provider" also sounds a little bit like a hierarchy. It does not suggest that notion of that partnership and just reinforces a distance. Consumerism is kind of defined by this transactional relationship, so you would use that term to reinforce that. I see how it has developed and how it's being pushed, and I think it's all related to the business of medicine versus the actual human experience and the humanity of medicine.

We so largely lost the 'care' in 'healthcare.

Topol: These terms got adopted when healthcare was transformed to a business, and now we're relooking at this.

Your work and eloquence and what you continue to do as an advocate in patient care will help us get back on track. It's just one of many things we need to do.

Topol: You also brought up the term "lean principles." It would be interesting for you to just touch on this as well.

Durrah: I've noticed in my work in healthcare thus far that health systems are adopting a lot of frameworks. One of these is becoming "lean" or utilizing "lean principles," which are driven by efficiency and cost savings.

Typically, those who advocate for lean principles within health systems say, "This is going to benefit everyone: physicians, nurses, patients and families, and the communities we serve." But if you really dig down deep, I don't think it has trickled down at all to any cost savings for patients or families. I don't think it's improved quality for communities which the healthcare system serves. And I certainly don't see physicians and nurses not being more burned out or more extended. They get affected by lean principles, where staffing is cut in order for that cost savings to occur. They are being told to do 150 things versus 100 things a day.

When I first learned about "lean" and read about it, I thought it sounded great. But then when I got deeper into this work, I thought, "Wait a minutewho is this benefiting other than the bottom line of healthcare systems?" It's really interesting how healthcare tends to cherry-pick principles or terminology from other industries with the goal of trying to improve healthcare, when it's really not doing that. It's simply putting a Band-Aid on one problem and creating a new one.

Topol: We so largely lost the "care" in "healthcare." You referred to the "care team." You undoubtedly experienced that with your daughter, and we want to bring it back. We should be more precise about language and avoid business terms, and talk about clinicians as doctors, nurses, pharmacists, physical therapists, or whoever. We should be more specific than using this "provider" term which obviously could be a relative or a friend.

Topol: What response did you receive from the essay you wrote in Health Affairs? It clearly resonated, and when I posted it on Twitter, there was quite a bit of response.

Durrah: I got an incredible response from the article, and I appreciate you tweeting and retweeting it because a lot of people saw that and reached out to me and started retweeting as well. A number of people sent me personal emails and messages, and I really was humbled by the response. I was quite nervous to write the article I did because in my work, there is kind of a fine line that you can only push the boundary so far, and then if you push them too far you get a lot of pushback. I sometimes feel like I'm this one little patient advocate voice among all these other voices. The article really resonated with physicians in particular, and they really understood the story which I shared about my daughter's liver doctor.

When we found out that she was diagnosed with cancer, she asked to sit in the meeting with the oncologists. She didn't have to do that, but she wanted to. I said, "Of course you can join us." She sat next to me and held my hand the entire meeting. Every time they said something distressing, she would just squeeze my hand, but she didn't utter a word. I think that encapsulates the relationship that patients and caregivers have with their physician or nurse. It's such a special bond, and the term "consumer" could never define that particular bond; she would never look at this as a transactional relationship. Would "consumer" teach her to do that? No. As you said before, it is the humanity and compassion of medicine, and that is why most everyone who comes into the profession really wants to help humanity and give that empathy and compassion.

We have a lot to learn, and it's going to take many voices to speak up and push back against consumerism because some pretty large organizations and groups are trying to push consumerism and continue this business imperative of healthcare that is motivated by bottom lines. I think we're going to get there. Maybe we're already there. We're at a tipping point. There is so much dissatisfaction, and so many parts of the system are broken. To say that consumerism will give you more choices, shorter wait times, and maybe even price transparency, even though you still have to deal with your insurance provider or lack thereof, makes me giggle because I don't think that is going to be the solution.

The only solution I see is that we have to partner with one another and co-create solutions to improve healthcare as teamsequal voices at the tableand begin this pushback. If we don't, I fear what is ahead because I've already had a glimpse of it. I'm nervous because as my daughter slowly moves into adulthood, and she is almost there, these were the things I hoped we would have conquered before she got to that point. A lot of this is pushing us away from one another and distancing ourselves from one another, and that is not going to change healthcare.

Topol: You said it so well. I've been eager to meet you since I read your work months ago, and I wanted the whole Medscape audience to get to know you and your story. Most of them are not on Twitter and most don't read Health Affairs. Your story is so darn important, and you convey it in a powerful way.

I'm so glad to know that your daughter is okay, having gone through 16 years of rough times, especially in her earlier years. I just want you to carry on. You are an important voice. You may qualify yourself as only one, but it's a powerful one, and very few people have had an experience like yours. You're in a rarified group and can transmit the emotion and the sense of caring. Let's get these words right, and let's zap "consumer" from this story of future healthcare.

Thanks so much for joining us today on Medscape, and we will look forward to following you and learning more from you in the future.

Durrah: Thank you. I look forward to partnering with your audience on improving healthcare.

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Healthcare Terms Are Out of Touch, Says Mom Advocate - Medscape