All Things Stem Cell

On August 5, 2013, a “lab-grown,” 5-ounce burger patty was taste tested in London, U.K. The patty had been grown from muscle stem cells that were isolated from cows. While this piece of “meat,” which was said to have tasted “close to meat,” represents significant progress in the field of making lab-grown food, the current approach needs to be improved before widespread use is feasible; the patty cost over $330,000 to make (not to mention probably significant culturing time in the lab to generate the 20,000 muscle strands used to make the patty). Luckily, there are many avenues that can be explored to optimize this technology. To understand them, it’s important to first understand the muscle stem cells themselves and how they’re cultured.

Origins of Muscle Stem Cells:
During development, the embryo has three different tissue types that, together with the germ cells, will make up the animal’s entire body. These are called the three germ layers. One of these tissue types, specifically the mesoderm, develops into skeletal muscle cells (along with other cell types, including cardiac muscle, kidney cells, red blood cells, and smooth muscle). Some stem cells that have been isolated from muscle appear to be mesenchymal stem cells. Mesenchymal stem cells (MSCs) got their name because they’re thought to primarily contain progenitors in the mesenchyme, which is a collection of cells mostly derived from mesoderm. (The majority of these cells later make up supportive structures throughout the body, such as bone, cartilage, connective tissue, muscle, adipose tissue, and the lymphatic and hematopoietic systems.) MSCs are typically multipotent, which means they can differentiate, or turn into, multiple different cell types. Specifically, MSCs are usually confirmed to be MSCs by showing that they can differentiate into three different, standard mesenchymal cell types: osteocytes (bone), chondrocytes (cartilage), and adipocytes (fat).

In muscle, there are two main groups of stem cells: satellite cells and muscle-derived stem cells (MDSCs) (Jankowski et al., 2002). Satellite cells were discovered decades ago (Mauro, 1961) and are commonly simply (and perhaps confusingly) referred to as muscle stem cells. It’s thought that these cells can regenerate damaged skeletal muscle and self-renew, but their ability to differentiate is rather limited; they can only make other types of muscle cells. (They’re basically unipotent.) MDSCs, on the other hand, are thought to be a type of multipotent mesenchymal stem cell and possibly a precursor of the satellite cells. But not only can the MDSCs differentiate into mesenchymal cell types, they have been found capable of becoming non-mesenchymal cell types as well. However, when picking the right stem cells to use for making lab-grown meat, the ability to differentiate into many different cell types is, for once, not an appealing trait.
Read more…

admin Mesenchymal Stem Cells clinical trials, developmental, lab-grown meat, muscle stem cells, news, vegetarians, xeno-free

International Stem Cell Awareness Day is October 3, 2012, so on this day please help spread the word about the importance of stem cell research! Stem cell researchers across the world are investigating how stem cells can be used to improve our lives, from repairing and regenerating damaged or lost tissues, to developing cures for numerous devastating diseases and conditions, such as cancer, Alzheimer’s, macular degeneration, Parkinson’s, and paralyzing spinal cord injuries, and various other useful applications in between: They’re being used to help us learn more about the entire developmental process (giving us a better understanding of how to fix problems that can arise during development), the efficacies of different drugs are studied and characterized using stem cells, and their unique biological roles make them ideal for use in better understanding aging.

So please be sure to get out the word on stem cells this October 3! For more information on International Stem Cell Awareness Day (and free wallpapers and downloadable stem cell images!), visit StemCellsOfferHope.com, which is affiliated with the Sue & Bill Gross Stem Cell Research Center at the University of California, Irvine. Read on for a summary of stem cell history and recent research breakthroughs and highlights.

With all of the breaking news stories that come out on cutting-edge stem cell findings all the time, it can be easy to lose sight of the bigger picture. Yes, the stem cell family, which includes all of the varieties of stem cells that have been discovered so far, is very large, and growing larger with new children, cousins, uncles, and aunts being discovered or created all the time. But a key feature they all share is their potential to improve our lives.

Our understanding of these cells and their incredible potential for treating diseases, fight cancers, heal wounds, and, in essence, saving lives, has grown hugely since we first unknowingly used them in World War II. However, the more we learn about them the more we realize we have yet to understand. This blog has strived to explore the different stem cell types in detail, including their biology, history, potential, clinical applications, and numerous remaining questions. However, the ways in which the different types of stem cells came to be accepted into the stem cell family is itself an interesting story, and one that can help paint a useful bigger picture, and that is why this story will be the focus for this blog post to celebrate International Stem Cell Awareness Day.

Read more…

admin Review bigger picture, Biology Bytes, cancer, clinical trials, developmental, embryonic, gene therapy, hematopoietic, history, mesenchymal, news, regenerative medicine, review

“STEM CELL REVOLUTIONS” is an informative and engaging documentary recently distributed by the Scottish Documentary Institute. It’s a very useful film to see if you want to learn more about the history of stem cells, and where the clinical, cutting-edge technology is at currently. The documentary gives an overview of international stem cell history, starting with the discovery of stem cells and ending with the newest members of the ever-growing stem cell family. To summarize such a wealth of research, research that has been going on for over half a century, the film tells the story of a few key stem cell discoveries and applications. Each story is described through interviews with stem cell researchers who were directly involved or appeared on the scene later but can knowledgably discuss the event’s impact. The first group of stories is related to adult stem cells (although this is not explicitly stated or explained): the discovery of stem cells during WWII, the amazing rescue of two boys in the early 1980s using stem cell-based skin grafts, and the present-day treatment of blind patients in a stem cell clinic in India. The final group of stories is related to pluripotent stem cells: the discovery of embryonic stem cells (ESCs) in mice in 1981 by Martin Evans (it was a treat to see Evans, who won the Nobel Prize in 2007 for the research he discusses in the film!) and of human ESCs (hESCs) in 1998 by Jamie Thomson, present-day use of hESCs to treat patients with retinal disorders in London (although I shuddered a little when Pete Coffee handled a flask of cells without gloves on!), and the creation of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006.

The science presented in the film is well-explained and even though the focus of the film is on medical breakthroughs accomplished using stem cells, the scientists interviewed do not try to over-hype current stem cell applications. Most helpful in making the technical information accessible are several short, accurate, and intriguing animations (made by Cameron Duguid). During a segment on Yamanaka’s research, one of these animations is particularly useful in explaining how chromatin regulation of gene expression is different in different types of tissues. However, it is repeatedly jarring when the interviews with down-to-earth stem cell scientists, who mostly do not over-hype their research, are bookended by interviews with Margaret Atwood (a writer who is confusingly repeatedly interviewed in a laboratory setting). She makes repeated references to The Fountain of Youth – at odds with the scientists’ messages. Similarly, repeatedly interspersed videos of a topless man doing what looked to be the Brazilian martial art of Capoeira seemed out of place.

Perhaps the only shortcoming of the film, if a bit minor, is that it shies away from getting into some of the nitty-gritty of why iPSCs may be better than hESCs or vice versa, but instead falls back upon the standard argument that hESCs are surrounded by ethical concerns. For a 71-minute-long film, it only makes sense that some issues be simplified, but additional details may have helped viewers better understand this important and hotly-debated topic. Specifically, a lot of the ethical arguments against hESCs are outdated or ill-founded. Probably most importantly, in 2006, Irina Klimanskaya and colleagues found how to isolate hESCs while leaving the donor embryo intact and potentially able to develop normally, weakening the argument against the generation of hESC lines on the grounds that they require the destruction of a potential embryo. Additionally, many researchers use blastocysts that would have been discarded by the in vitro fertilization clinic because the embryos were damaged in some way and would never develop properly. However, a significant strike against using hESCs in treatments, which the film does not touch upon, is the potential for immune rejection. Human iPSCs, on the other hand, are very appealing because they potentially may not have immune rejection problems in treatments, as mentioned in the film. However, human iPSCs are much newer to the stem cell scene and have similarities with cancer cells that researchers should probably better understand before iPSCs are widely used clinically. It is also a little surprising that Jamie Thomson is not mentioned in the human iPSC segment, as his group independently created human iPSCs at the same time as Yamanaka’s group.

The researchers interviewed in the film emphasize the importance of striking a balance between regulation and progress, but then the film seems to not take its own advice and gets bogged down in the regulation of stem cells in the very last segment of the film, when it may have been more useful to focus on the near-future applications of these cells. There’s a surprising focus on the hypothetical ethical arguments that would arise should human iPSCs be made into function eggs and sperm (which has not been done yet, and may not even be possible). However, it may be more useful to first focus on whether human iPSCs can even be successfully used in the clinic before diverting attention to this hypothetical ethical argument, which is much further down the road. It would also have been nice to see a mention of direct reprogramming, the latest stem cell technology that may one day make even iPSCs obsolete.

While there are amazing advances being made with stem cell technology, the film rightly cautions viewers about the dangers of going to a stem cell clinic abroad. A great resource for those considering stem cell treatments abroad is A Closer Look at Stem Cell Treatments, a website made by the reputable International Society for Stem Cell Research.

Overall, “STEM CELL REVOLUTIONS” is a great film for anyone wanting to learn more about the history of stem cells, hear legendary researchers talk about their ground-breaking work and patients talk about how stem cell therapies have changed their lives, and still get a down-to-earth idea of what is realistically being accomplished with these cells.

admin Bioengineering, Embryonic Stem Cells, Hematopoietic Stem Cells, Reprogramming, Review adult, clinical trials, embryonic, history, regenerative medicine, review

While there is great potential for using stem cells in regenerative therapies, there is still a ways to go before it can be considered a proven practice, although recent breakthroughs, and one specific trial in particular, makes it seem much closer. Recently, the first human tissue-engineered organ using stem cells was created and transplanted successfully into a patient. Other tissue regeneration efforts with stem cells have also recently made many breakthroughs, emphasizing the potential of using stem cells in future tissue transplants.

In the first reported instance of using stem cells to bioengineer a functional human organ, Paolo Macchiarini and his research group used a patient’s own stem cells to generate an airway, specifically a bronchus, and successfully grafted it into the patient to replace her damaged bronchus (See Figure 1). Macchiarini’s group bypassed the problem of immune rejection by using the patient’s own stem cells. Additionally, by combining a variety of bioengineering efforts, no synthetic parts were involved in the creation of the organ; it was made entirely of cadaveric and patient-derived tissues (Macchiarini et al., 2008; Hollander et al., 2009).

Figure 1. In order to create a patient-compatible replacement bronchus, Macchiarini’s group removed and decellularized a trachea from a cadaveric donor, grew cells removed from the patient on the trachea in a bioreactor, and then transplanted the bioengineered airway into the patient, successfully replacing their defective bronchus (Macchiarini et al., 2008).

Read more…

admin Bioengineering, Mesenchymal Stem Cells adult, clinical trials, mesenchymal, regenerative medicine

Human embryonic stem cells (hESCs) recently celebrated the 10th anniversary of their discovery, and in the decade since their isolation they have possibly received more press coverage, both over their many potential applications as well as ethical concerns, than any other type of stem cell. In the last decade, much progress has been made in better understanding these cells and their capabilities. hESCs hold much promise not only for being cellular models of human development and function, but also for use in the field of regenerative medicine. However, due to ethical and application concerns, only recently have these cells made it to clinical trials.

Figure 1: The Blastocyst. Human embryonic stem cells are isolated from early-stage embryos in the late blastocyst stage, about four or five days after fertilization. The blastocyst is a hollow sphere made of approximately 150 cells and contains three distinct areas: the trophoblast, which is the surrounding outer layer that later becomes the placenta, the blastocoel, which is a fluid-filled cavity within the blastocyst, and the inner cell mass, also known as the embryoblast, which can become the embryo proper, or fetus, and is where hESCs are isolated from.

Though human embryonic stem cells were isolated just over a decade ago, embryonic stem cells were successfully isolated from other animals before this. Nearly 30 years ago, two groups independently reported the isolation of mouse embryonic stem cells (mESCs) (Martin, 1981; Evans and Kaufman, 1981). The mESCs were isolated from early-stage mouse embryos, approximately four to six days post-fertilization (out of 21 days total for mouse gestation). At this point in development, the embryo is in the late blastocyst stage (see figure 1). It was not until the mid-1990s that this feat was accomplished with non-human primates by Dr. James Thomson’s group (Thomson et al., 1995). Only a few years later, embryonic stem cells isolated from humans, once again by Thomson’s group, in 1998 (Thomson et al., 1998).

It is important to understand where hESCs come from in order to understand the ethical arguments that surround them, as well as their enormous, innate biological potential. Like mESCs, hESCs are isolated from early-stage embryos that are, specifically, in the late blastocyst stage, about four or five days after fertilization. After the fertilized egg cell starts cell division, what is referred to as the “blastocyst” occurs once the cell has divided into a hollow sphere made up of approximately 150 cells (see figure 1). At this point, the embryo has not even yet been implanted in the uterus. The blastocyst contains three distinct areas: the trophoblast, which is the surrounding outer layer that later becomes the placenta, the blastocoel, which is a fluid-filled cavity within the blastocyst, and the inner cell mass, also known as the embryoblast, which can become the embryo proper, or fetus. Embryonic stem cells can be created from cells taken from the inner cell mass (Stem Cell Basics: What are embryonic stem cells?, 2009). Because these cells are taken from such an early stage in development, they have the ability to become cells of any tissue type (except for the whole embryo itself), making them pluripotent. The pluripotency of hESCs is probably the trait that contributes most to their enormous potential, both as models of cell function and human development and, potentially, for uses in regenerative medicine. Being pluripotent and seemingly unlimited in supply separates hESCs from adult stem cells, which are multipotent or unipotent, able to become a more select group of cell types, and more limited in their cellular lifespan.

Read more…

admin Embryonic Stem Cells clinical trials, embryonic, history, news, regenerative medicine