Stem cell research has risen from humble beginnings to a whirlwind of discovery that has captured both the attention of the media and the imagination of the public. This article will provide an introduction to stem cells, describe some of the vital scientific concepts involved in stem cell research and cover a brief history of the major research milestones. It will then outline the requirements for stem cell therapy and describe both the technical and non-technical challenges of stem cell research. Finally, it will provide updates on how stem cells are being used in applications ranging from aging research to diabetes, and give insight on recent novel approaches used to this new era of stem cell innovation.
There are three categories of cells in the human body: somatic cells, germ cells and stem cells. Somatic cells are differentiated, specialized cells that compose the vast majority of the human body. Germ cells produce the reproductive cells of eggs and sperm that can unite to form a fertilized egg. By definition, stem cells are cells that have the ability to continuously replenish and divide in culture, and can further differentiate into specialized cell types.
When a stem cell divides, the offspring cells have two options: self-renewal or differentiation.
The first option is a pure replication. A stem cell divides into two stem cells that are equivalent to the parent, thus ensuring an adequate supply of available stem cells in that part of the body.
The second option is differentiation, where the daughter cell appears more specialized towards a certain function, in comparison to its stem cell parent. With each subsequent cell division, there is increasing specialization from a stem cell toward a final somatic cell. This stem wise progression is termed a “stem cell lineage”. An example in the body is the bone marrow. There is a bone marrow stem cell that, through a series of stepwise intermediates, can become a red blood cell or one of several types of white blood cells.
The “stem” nomenclature is thus analogous to a stem seen on a flower. Stem cells at the bottom of the plant can either continue down the straight path and continue as a stem cell, or else “branch off” the stem at any of a number of points to become one of several types of differentiated cells.
There are several types and origins of stem cells that are used in stem cell research.
The first case to consider is the fertilized egg, which has the ability to divide and differentiate into all the tissues of the developing human. While the fertilized egg and the initial few divisions thereafter do contain the information to make the entire organism, they do not in practice have the capability to self-renew. Therefore, by our strict definition above, they are not true stem cells. Instead, one needs to dissect the early embryo at the blastocyst stage, and isolate part of it called the “inner cell mass” (ICM). These cells of the inner cell mass, when cultured on a suitable feeder medium in vitro, can self-renew indefinitely and are thus theoretically immortal. These are embryonic stem cells.
The next type of stem cell is the germ cell, which are less important clinically. Primordial germ cells are transient stem cells that exist in the embryo before irreversibly committing to full germ cells upon association with somatic cells in the gonads. A subtype of primordial germ cell is called a human embryonic germ cell. Human embryonic germ cells can be isolated from primordial germ cells from a fetus that is 5-9 weeks old (Shamblott, 2001).
There is a pathological type of stem cell called an embryonic carcinoma cell. These are neoplastic cells that can develop into many types of tissue from within a teratoma or teratocarcinoma. These are further described in the Teratoma and teratocarcinoma section.
Fetal stem cells are found in the developing embryo and give rise to the various organs of the body. These include cells such as pancreatic islet progenitor cells (Beattie, 1997), neural crest stem cells (Villa, 2000) and fetal hematopoietic stem cells. Fetal hematopoietic stem cells can be obtained from umbilical cord blood, placenta, and fetal blood. There has been a rise in commercial capture and storage of umbilical cord blood because of relatively few ethical concerns. Cord blood stem cells are a good choice for pediatric patients. In adults, cord blood is more problematic since the cord blood collection can only be done once, and there is only a small number of hematopoietic progenitors in the cord blood (Chao, 2004).
Finally, there are adult stem cells, which are found in many types of tissue. These stem cells replace cells that are constantly being turned over. For example, sloughed-off skin is replaced by epidermal stem cells, the gut wall is replaced by intestinal crypt cells and some nervous tissue is replaced by neuronal stem cells (Spradling, 2001). The best-studied examples are hematopoietic stem cells and mesenchymal stem cells, both of which exist in bone marrow. Hematopoietic stem cells replace lost blood cells, and mesenchymal stem cells respond to injury to replace bone, cartilage, tendon and other connective tissues (Short, 2003). Adult stem cells have dominated much of human clinical trials due to their ease of culture and bypassing of ethical concerns.
Several animals within the invertebrate phyla, for example the planarian flatworm, are able to reform vast missing sections of their body. Some amphibians are able to regenerate tails or other limbs after traumatic injury
Humans are able to regenerate certain aspects of their physique, such as the various blood cells, skin and others. However, humans and most other higher vertebrates are incapable of regenerating an entire organ or limb, despite the fact that the human DNA contained the relevant instructions for composing those tissues over the course of fetal development. (Bongso, 2004). However, there are some exceptions. For example, the human liver has an unusual ability to regenerate after partial removal.
Due to safety and ethical concerns, a significant portion of stem cell research has been carried out on animal models, usually either mouse or monkey. Some of the research involves cross species transplants, such as implantation of human stem cells into the spinal cords of mice. While many of the findings from animal models are transferable to human therapeutics, one must bear in mind that full human trials are required before any medical strategy can be seen in modern clinics.