All Things Stem Cell

Induced pluripotent stem cells (iPSCs) have enormous potential for being used in tissue transplants and therapies. Why is this? It’s because iPSCs can be made using virtually any cells from a person’s body — such as skin or fat samples that wouldn’t be missed. (And since they’re the patient’s own cells, the immune system should not reject them in a transplant.) iPSCs are also pluripotent, which means they can be turned into nearly any cell type. This means that if a patient needs a certain type of retinal cell to treat an eye disease, a skin sample could be taken, turned into the desired retinal cells, and then transplanted into the patient’s eye. And this is exactly what happened for the first time last week.

Even though human iPSCs were first created in late 2007, it wasn’t until last week that they were used in a tissue transplant in a human for the first time. The person was a Japanese woman in her 70s, and the iPSC-derived cells were used to treat her age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Safety studies in mice and monkeys had been previously done to ensure the iPSCs would not cause tumors or be rejected by the immune system.
Read more…

admin Induced Pluripotent Stem Cells

Recently, many papers have come out that highlight connections between cancer and induced pluripotent stem cells (iPSCs), the latter of which was discussed previously. These papers hold many implications for not only iPSCs, but for our understanding of cancer as well. Additionally, these papers should not at all be thought of as invalidating the importance of iPSCs for studying and treating future therapies, but they should help us better understand what iPSCs are and how to use them appropriately.

The most recent and most publicized link between iPSCs and cancer is p53. p53, also known as protein 53 (53 referring to its molecular mass), is a well-studied protein whose normal function is important in preventing cancer. Though p53 has many different roles, they are quite related. In essence, the job of p53 is to make sure the cell does not accumulate DNA damage, or DNA mutations, which could eventually make the cell cancerous. When a cell has its DNA damaged, often from external stresses, p53 stops the normal cell cycle to fix the DNA damage. If the damage is too great to repair, p53 can prevent the cell from dividing, which would create more damaged cells; p53 initiates programmed cell death, or apoptosis. The potential tumor cell dies. Overall, p53 functions as a “tumor suppressor” to prevent abnormal cells from occurring and multiplying into a cancer (Vazquez et al., 2008). Consequently, it has been found that p53 is mutated in approximately 50% of all human tumors, and other tumors may have mutations in the pathway regulating p53 activity (Vazquez et al., 2008). p53 is therefore well-studied as an oncogene, or a gene that when not functioning normally can contribute to a normal cell becoming cancerous.

So what does p53 have to do with iPSCs? One recently discovered connection is with the generation of iPSCs. Recently, many research groups discovered that when p53 is deleted from, or damaged in, their cells, they could more easily become iPSCs (Hong et al., 2009; Kawamura et al., 2009; Utikal et al., 2009; Li et al., 2009; Zhao et al., 2008). As posted earlier, iPSCs are cells that were originally from adult tissues, but have been “reprogrammed” to be pluripotent stem cells, or stem cells able to become all the adult cells of the body, looking and functioning nearly identical to human embryonic stem cells (hESCs) (Takahashi et al., 2007; Yu et al., 2007).

Read more…

admin Cancer Stem Cells, Embryonic Stem Cells, Induced Pluripotent Stem Cells adult, cancer, embryonic, news, regenerative medicine

Virtually identical to human embryonic stem cells (hESCs) except for their origin of isolation, the recently created induced pluripotent stem cells (iPSCs) (Yu et al., 2007; Takahashi et al., 2007) hold much potential for use in regenerative therapies. iPSCs are cells that were originally from adult tissues, but have been forced to produce proteins that are thought to be essential for the pluripotency of human embryonic stem cells. By making cells express these embryonic stem cell proteins, adult cells can be created that look and act nearly identical to hESCs.

Applying Somatic Cell Nuclear Transfer in the Creation of Dolly the Cloned Sheep. Dolly the sheep was cloned through somatic cell nuclear transfer (SCNT). An adult cell from the mammary gland of a Finn-Dorset ewe acted as the nuclear donor; it was fused with an enucleated egg from a Scottish Blackface ewe, which acted as the cytoplasmic (or egg) donor. An electrical pulse acted to fuse the cells and activate the oocyte after injection into the surrogate mother ewe. A successfully implanted oocyte developed into the lamb Dolly, a clone of the nuclear donor, the Finn-Dorset ewe.

The idea of reprogramming a cell from adult tissue into an embryonic-like, pluripotent cell existed long before the creation of iPSCs. In 1938, Hans Spemann showed that a nucleus from a fertilized salamander egg that had already undergone cell division several times could be implanted into a cell from a newly fertilized salamander egg that is enucleated (has had its nucleus removed) and create an entire adult salamander (Spemann, 1938). Consequently, Spemann’s work suggests that an embryonic nucleus remains totipotent, or is able to develop into any cell type of the adult body, even after several cell divisions. Due to technical difficulties, it was several years before researchers could repeat these experiments using older nuclei to see how long the nucleus retains its pluripotency. In the early 1950s, Robert Briggs and Thomas King repeated Spemann’s experiments using a species of leopard frog, Rana pipiens, first with a nucleus from young embryos (Briggs and King, 1952) then from older embryos (King and Briggs, 1954); both the younger and older implanted nuclei could still be reprogrammed by the enucleated host cell. However, they also observed that the older the donor nucleus was, the more difficult it was to reprogram it to a totipotent state. For years it was unclear whether the nucleus from a fully differentiated, adult cell could be completely reprogrammed, as conflicting results were published by different groups (Briggs and King, 1957; Fishberg et al., 1958; Gurdon and Byrne, 2003).

Although the studies done by Spemann, Briggs, and King used nuclei from embryos, their results are the basis for somatic cell nuclear transfer (SCNT). SCNT is a technique wherein the nucleus from a somatic cell (an adult cell that is not a sperm or egg, i.e. not the gametes) is implanted into an enucleated egg cell which can then be implanted into, and develop in, a surrogate mother, and potentially become an adult organism. The resultant organism is a clone of the animal that donated the nucleus. The first widely-accepted successful use of SCNT came with the creation of the sheep Dolly in 1997, the first cloned animal from an adult cell and the first cloned mammal (Wilmut et al., 1997). Since then, several other animals have been successfully cloned, though many problems still remain and there are low success rates (Wilmut et al., 1997; Wakayama et al., 1998; Solter, 1998; McKinnell and Di Bernardino, 1999; Gurdon and Byrne, 2003).

Read more…

admin Embryonic Stem Cells, Induced Pluripotent Stem Cells adult, embryonic, history, news

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