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Human embryonic stem cells, shown growing in a "colony" in the middle of the picture above, have been an essential addition to the ever-growing stem cell family.

Human embryonic stem cells, shown growing in a "colony" in the middle of the picture above, have been an essential addition to the ever-growing stem cell family.


The Stem Cell Family

A Bigger-Picture View


Friday, June 11, 2010

With all the breaking news stories on cutting-edge stem cell findings, 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 we’ve 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, fighting cancers, healing wounds, and, in essence, saving lives, has grown hugely since we first unknowingly used stem cells in World War II.

However, the more we learn about them the more we realize we have yet to understand. This column, Biology Bytes, 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.

Hematopoietic Stem Cells: 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).

Because hematopoietic stem cells 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 hematopoietic stem cells are one of the few types of adult stem cells that are widely used clinically.

Embryonic Stem Cells: 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) are isolated from early stage embryos. Technically called blastocysts, these are the embryos that are 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.

Mesenchymal Stem Cells: 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, 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 hematopoietic stem cells 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 the presence of dental pulp stem cells in teeth.

Newest Family Additions: During the last decade, a number of new stem cell types have joined the ever-growing family, through discovery or creation. In 2007, stem cells were found to reside in menstrual blood. It’s unclear exactly what branch these “endometrial regenerative cells” belong to in the stem cell family; they have similarities with both embryonic stem cells and mesenchymal stem cells. 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), are created by forcing adult cells to produce proteins specific to embryonic stem cell 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. It was found that a variety of cells could have their “established” identities altered, 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. Just this year, another group found that fibroblast cells (cells active in connective tissue) taken from mouse tails could be made into nerve cells, or neurons.

So What have Stem Cells Done for You Lately?

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

Engineering Organs: In 2008, Claudia Castillo had her near-collapsed bronchus replaced by a trachea from a cadaver. The trachea had her own cells grown on it. These cells included chondrocytes (cartilage cells) that were made from mesenchymal stem cells 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.

Treating HIV: Although hematopoietic stem cells have been used since World War II to treat victims of radiation, a potential, significant new application was reported just last year: Hematopoietic stem cells were used to successfully treat a patient with HIV, although the procedure is currently risky and much additional research is necessary for it to be widely accepted and used.

Treating Spinal Cord Injuries: 2009 also saw the first FDA-approval of the use of human embryonic stem cells in a clinical trial. Hans Keirstead, who will be talking in Santa Barbara on Monday, June 14, developed the therapy to be used in the trial; Keirstead and colleagues made hESCs become oligodendrocytes, and then showed that these cells could help cure spinal cord injuries in animals. This trial holds 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.

Fighting Cancer: Stem cells have also helped us better understand cancer, through investigation of the emerging idea of the cancer stem cell and the many similarities cancer shares with different members of the stem cell family. Such studies may even help researchers develop better cancer vaccines.

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.

For more on the different stem cell types, see a variety of previous Biology Bytes articles, including ones on hematopoietic stem cells, human embryonic stem cells, mesenchymal stem cells, endometrial regenerative cells, induced pluripotent stem cells, direct reprogramming, bioengineering organs, treating HIV with stem cells, Hans Keirstead, cancer stem cells, and cancer vaccines.

Biology Bytes author Teisha Rowland is a science writer, blogger at All Things Stem Cell, and graduate student in molecular, cellular, and developmental biology at UCSB, where she studies stem cells. Send any ideas for future columns to her at science@independent.com.

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