All Things Stem Cell

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.

The first time stem cells were successfully used to treat patients was during World War II. However, at the time, people did not know they were using stem cells. During World War II, people exposed to lethal doses of radiation were given bone marrow transplants that, somehow, could cure them. Much later it was discovered that the responsible agents in the bone marrow were hematopoietic stem cells (HSCs) (which have been discussed in several blog posts). Because HSCs are rapidly growing cells, they’re particularly damaged by exposure to radiation. Consequently, a radiation victim may need a transplant of healthy HSCs to replace their own. As this history makes apparent, HSCs reside in bone marrow (as well as other tissues), making bone marrow a good HSC transplantation source.

But what do these HSCs do exactly? They’re quite important. They can turn into all the different types of blood cells in the body. This is why transplants of HSCs (from bone marrow) are also used to treat cancers of the hematopoietic (blood) system, such as leukemia or lymphoma. Today HSCs are one of the few adult stem cells that are widely used clinically.

While bone marrow donor centers were being established in the 1980s, another stem cell family tree branch was developing that would draw much attention: Nearly 30 years ago, embryonic stem cells were isolated from early-stage mouse embryos. It was not until 1998 that the same feat was accomplished with human embryos, by James Thomson, who holds a faculty appointment at the University of Wisconsin and the University of California at Santa Barbara.

These human embryonic stem cells (hESCs), which have been discussed in numerous blog posts, are isolated from early stage embryos. Technically called blastocysts, these are embryos that have not yet implanted in the uterus. They have existed for only five days after fertilization and contain only about 150 cells. One of the most promising qualities of hESCs is their ability to become virtually any cell type; this potential means they are “pluripotent.” As we’ll see later on, this has already contributed to their receiving FDA-approval for use in a clinical trial.

Around the same time that researchers were figuring out how to isolate embryonic stem cells from humans, yet another large group of stem cells was finally admitted into the stem cell family. Although researchers reported the existence of mesenchymal stem cells (MSCs) as early as the 1960s and 1970s, as discussed in a previous blog post, they were excluded from the stem cell family for decades. Why the prejudice? MSCs had somewhat questionable origins; they’re most commonly harvested from adipose tissue (fat) or bone marrow. Researchers already knew bone marrow was home to HSCs and it was difficult to accept that they shared their home with yet another group of stem cells. But by the late 1990s, MSCs were firmly established and allowed into the family.

MSCs hold great potential for the field of regenerative medicine, as they can become many different types of cells (they’re “multipotent”), most typically bone, cartilage, and fat cells. In 2000, a new member was added to the mesenchymal stem cell branch, when researchers discovered that teeth are home to dental pulp stem cells, which were explored in a previous blog post.

During the last decade, a number of new stem cell types have joined the every-growing family, through discovery or creation. In 2007, stem cells were found to reside in menstrual blood, as covered previously. It’s unclear exactly what branch these “endometrial regenerative cells” belong to in the stem cell family; they have similarities with both ESCs and MSCs. Nonetheless, because they can be obtained in a non-invasive manner, and in large quantities, they offer much potential for cellular therapies.

2007 also saw one of the most game-changing developments in the stem cell field; researchers learned how to create cells like embryonic stem cells, but instead of coming from an embryo these cells are created from adult cells, potentially cells from any tissue in the human body. These cells, called induced pluripotent stem cells (iPSCs), which were discussed in several previous blog posts, are created by forcing adult cells to produce proteins that are specific to ESC functions, causing the adult cells to look and act like ESCs. iPSCs have significantly altered the field ethically, as they have the utility of embryonic stem cells but do not require harvesting cells from a blastocyst. They also alter it clinically: It’s now possible, in theory, to grow patient-specific pluripotent cells.

But the idea of changing a mature cell’s identity had already been around for a few decades. Since the late 1980s, researchers had used “direct reprogramming” to, for example, make different types of adult cells turn into muscle cells. They did this by making the adult cells produce proteins essential to the identity of muscle cells, which was discussed in a previous blog post. It was found that other cells could have their “established” identities altered in similar ways, with a group in 2008 reporting that some pancreas cells (exocrine cells) could be turned into other, insulin-producing pancreas cells (beta-cells), which may hold promise for treating diabetes. In 2010, another group found that fibroblast cells (cells active in connective tissue) taken from mouse tails could be made into nerve cells, or neurons.

Although many stem cell therapies are still in their infancy, in the last few years there have been several important publications on the successful use of novel stem cell treatments in patients.

In 2008, Claudia Castillo had her near-collapsed bronchus replaced by a trachea from a cadaver that had her own cells grown on it, which was discussed in detail in another blog post. These cells included chondrocytes (cartilage cells) that were made from MSCs that had been taken from her bone marrow; turning these MSCs into chondrocytes only took researchers three days. Since 2008, this technique has been improved upon and successfully used in other patients.

Although HSCs have been used since World War II to treat victims of radiation, a potential, significant new application was reported in 2009: HSCs were used to successfully treat a patient with HIV, which was discussed previously, although the procedure is currently risky and much additional research is necessary for it to be widely accepted and used.

2009 also saw the first FDA-approval of the use of hESCs in a clinical trial, with the first patients receiving treatment in 2010. Hans Keirstead and colleagues developed the spinal cord therapy used in the clinical trial; they made hESCs become oligodendrocytes and then showed that these cells could help cure spinal cord injuries in animals. StemCells Inc. and collaborators at the Sue & Bill Gross Stem Cell Research Center announced at a meeting in September, 2012, that some patients with spinal cord injuries in a clinical trial regained some capacity to feel heat and touch. These trials hold much promise not only for those with spinal cord injuries, but for other hESC-based therapies that may now have a better chance at receiving FDA-approval for clinical trials.

Stem cells have also helped us better understand cancer, through investigation of the emerging idea of the cancer stem cell, which has been discussed multiple times before, and the many similarities cancer shares with different members of the stem cell family. Such studies may even help researchers develop better cancer vaccines, also as previously discussed.

And that’s not all that stem cells have done. Here are a few more recent stem cell research highlights:

• Studying stem cells may have provided us with a key to understanding male pattern baldness, as discussed in a previous blog post.
• Stem cells are used to help us understand the toxicity of different compounds on different tissues, as outlined in this article, and as recently published using ESCs.
• Just one recent example of the many diseases that stem cells are being used to treat: A patient with tumors caused by the human papillomavirus (HPV), specifically recurrent respiratory papillomatosis with tumor invasion, had normal and tumorous cells removed and reprogrammed to create cell cultures. The researchers found that the HPV genome was normal in the normal cells, but much larger in the tumorous cells, due to the presence of multiple oncogene regions. Findings such as this may help us better treat complications caused by HPV, and other viral, infections.
• Another stem cell member may be tentatively added to the family with the characterization of cells that generate esophageal tissue.

As our understanding of this complex and constantly growing family continues to grow, so too should our understanding of how the medical field can best use the different members to improve our lives. So, again, on this October 3 please be sure to spread the word on the amazing research being done with stem cells! For more information on International Stem Cell Awareness Day and free stem cell images, visit StemCellsOfferHope.com.

References:

California Institute for Regenerative Medicine (CIRM). CIRM grantees show preliminary signs of success in spinal cord injury trial. September 4, 2012. View Article

Chi, K. R. Stemming the Toxic Tide: How to Screen for Toxicity Using Stem Cells. The Scientist. September 2, 2012. View Article

Kushner, J. A. Esophageal Stem Cells, Where Art Thou? Development. August 31, 2012. View Article

Rowland, T. J. A Night with Dr. Hans Keirstead. Santa Barbara Independent: Biology Bytes. June 4, 2010. View Article

Rowland, T. J. The Stem Cell Family. Santa Barbara Independent: Biology Bytes. June 11, 2010. View Article

Seiler, A. E. M., and Spielmann, H. The validated embryonic stem cell test to predict embryotoxicity in vitro. Nature Protocols. June 16, 2011. View Article

StemCellsOfferHope.com. Sue & Bill Gross Stem Cell Research Center, University of California, Irvine.

Yuan, H., Myers, S., Wang, J., et al. Use of Reprogrammed Cells to Identify Therapy for Respiratory Papillomatosis. The New England Journal of Medicine. September 27, 2012. View Article

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