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Mini Medical Dictionary

beta islet cells
Beta islet cells

Beta islet cells: (pancreas) Cells found in the pancreas. These cells produce the hormone insulin.  When islet cells fail or are destroyed, diabetes results.

human blastocyst
Human blastocyst

Blastocyst: A hollow structure in early embryonic development that contains a cluster of cells. This cluster is called the inner cell mass and is which the embryo begins.

Differentiated:  (when referring to biology) - Having biological specialization; adapted during development to a specific function or environment

mouse stem cells
Stem cells (mouse)

Stem cell:  A cell from which other types of cells (including other stem cells) can develop.

Adult stem cells come from adults and young adults.

Cord blood stem cells come from the placenta and umbilical cord; they are a source of adult stem cells

Embryonic stem cells come from a blastocyst, a cell structure from which an embryo develops.

Undifferentiated:  
(when referring to biology) -
Term used to describe cells or tissues that do not have specialized ("mature") structures or functions.


Notes

(1) National Institutes of Health, "Stem Cell Basics," July 19, 2004.

(2) Vacanti MP, Roy A, Cortiella J, Bonassar L, Vacanti CA (2001). "Identification and initial characterization of spore-like cells in adult mammals". J Cell Biochem 80 (3): 455-60. PMID 11135375.

(3) National Institutes of Health, Stem Cell FAQ, April 13, 2005.

(4) Graham, Judith and Schodolski, Vincent J., "Son of former President Reagan enters the fray with a speech at the Democratic convention." Chicago Tribune, July 27, 2004

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What are stem cells?
Information for this article, though edited content, is from Wikipedia.com


Mini Site Index
What are stem cells?
Why not use other cells?
Types of Stem Cells
About Cord Blood Stem Cells
About Adult Stem Cells
About Embryonic Stem Cells
About Spore-Like Cells  

  stem cell
     Human stem cell

What are stem cells?

Stem cells are primal undifferentiated cells (cells that do not have a specialized or "mature" function) and retain the ability to differentiate (adapt or change to serve a specific function or environment)  into other cell types. More simply stated, stem cells can become other types of cells to help the body where needed.  This ability allows them to act as a repair system for the body, replenishing other cells as long as the organism is alive.

Medical researchers believe stem cell research has the potential to change the face of human disease by being used to repair specific tissues or to grow organs. Yet as government reports point out, "significant technical hurdles remain that will only be overcome through years of intensive research."(1)

The study of stem cells is attributed as beginning in the 1960s after research by Canadian scientists Ernest A. McCulloch and James E. Till.  


Why not use other cells?

Stem cells are like templates; they are master cells that can grow into many other types of cells. They can serve a “repair” function in the body because in theory, they can divide without limitation to replenish other cells that have been damaged. This is because stem cells have a unique ability:  when they divide they can either remain a stem cell or become another type of cell such blood, muscle, or even brain cells.

No other cell in the body can perform the same function that stem cells do.  Other cell types cannot replicate stem cells, or convert into other cell types.  This makes stem cells a focus for researchers because of the potential for stem cells to someday be stimulated into replacing pancreatic beta islet cells destroyed by diabetes. 

Embryonic stem cells are capable of reproducing for a long time (up to one year) unlike adult stem cells which cannot match the prolific replication life span of embryonic stem cells.  


Types of Stem Cells

Stem cells are categorized by potency which describes the specificity of the cell.

  • Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg cell are also totipotent. These cells can grow into any type of cell without exception.
  • Pluripotent stem cells are the descendants of totipotent cells and can grow into any cell type except for totipotent stem cells.
  • Multipotent stem cells can produce only cells of a closely related family of cells (e.g. blood cells such as red blood cells, white blood cells and platelets).
  • Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells.

Stem cells are also categorized according by their source, as either adult or embryonic:

  • Adult stem cells are undifferentiated cells found among differentiated cells of a specific tissue and are mostly multipotent cells. They are already being used in treatments for over one hundred diseases and conditions. They are more accurately called somatic (Greek, meaning "body") stem cells, because they need not come from adults but can also come from children or umbilical cords. Particularly interesting are adult stem cells termed "spore-like cells". They are present in all tissues (Vacanti, M. P., A. Roy, J. Cortiella, L. Bonassar, and C. A. Vacanti. 2001. "Identification and initial characterization of spore-like cells in adult mammals." J Cell Biochem 80:455–60.) and seem to survive long time periods and harsh conditions.
     
  • Embryonic stem cells are cultured cells obtained from the undifferentiated inner mass cells of a blastocyst, an early stage embryo that is 50 to 150 cells. Embryonic stem cell research is "thought to have much greater developmental potential than adult stem cells," according to the National Institutes of Health.(3) However, embryonic stem cell research is still in the basic research phase, as these stem cells were first isolated in 1998 (at least for humans), whereas adult stem cells have been studied since the 1960s.(4) Research with embryonic stem cells derived from humans is controversial because, in order to start a stem cell 'line' or lineage, it requires the destruction of a blastocyst (human embryo), which many believe is tantamount to the destruction of a human being.  


About Cord Blood Stem Cells

Blood from the placenta and umbilical cord that are left over after birth is one source of adult stem cells. Since 1988 these cord blood stem cells have been used to treat Gunther's disease, Hunter syndrome, Hurler syndrome, Acute lymphocytic leukemia and many more problems occurring mostly in children. Umbilical cord blood use has become so common that there are now umbilical cord blood banks that accept donations from parents. It is collected by removing the umbilical cord, cleansing it and withdrawing blood from the umbilical vein. This blood is then immediately analyzed for infectious agents and the tissue-type is determined. The cord blood is processed and depleted of red blood cells before being stored in liquid nitrogen for later use, at which point it is thawed, washed of the cryoprotectant, and injected through a vein of the patient. This kind of treatment, where the stem cells are collected from another donor, is called allogeneic treatment. When the cells are collected from the same patient on whom they will be used, it is called autologous and when collected from identical individuals, it is referred to as syngeneic. Xenogeneic transfer of cells (between different species) is very underdeveloped and is said to have little research potential.


About Adult Stem Cells

Stem cells can be found in all adults and young adults. Adult stem cells are undifferentiated cells that reproduce daily to provide certain specialized cells—for example 200 billion red blood cells are created each day in the body from hemopoietic stem cells. Until recently it was thought that each of these cells could produce just one particular type of cell—this is called differentiation (see Morphogenesis). However in the past few years, evidence has been gathered of stem cells that can transform into several different forms. Bone marrow stromal stem cells are thought to be able to transform into liver, nerve, muscle, hair follicle and kidney cells. Although there is some evidence that this type of transdifferentiation can occur, many scientists are skeptical of these claims and we are still learning about such transdifferentiated cells.


 Mouse Stem Cells

Adult stem cells may be even more versatile than this. Researchers at the New York University School of Medicine have extracted stem cells from the bone-marrow of mice which they say are pluripotent. Turning one type of stem cell into another is called transdifferentiation.

In fact, useful sources of adult stem cells are being found in organs all over the body. Researchers at McGill University in Montreal have extracted stem cells from skin that are able to differentiate into many types of tissue, including neurons, smooth muscle cells and fat-cells. These were found in the dermis, the inner layer of the skin. These stem cells play a pivotal role in healing small cuts. Blood vessels, the dental pulp, the digestive epithelium, the retina, liver and even the brain are all said to contain stem cells.

The Tulane University Center for Gene Therapy is the first U.S. government-funded center to produce and distribute well-characterized adult stem cells to researchers around the globe. These standardized cells are critical to ensuring comparability and reproducibility of world-wide research.

Adipose derived adult stem (ADAS) cells have also been isolated from fat, e.g. from liposuction. This source of cells seems to be similar in many ways to Mesenchymal stem cells (MSCs) derived from bone marrow, except that it is possible to isolate many more cells from fat. These cells have been shown to differentiate into bone, fat, muscle, cartilage, and neurons. These cells have been recently used to successfully repair a large cranial defect in a human patient.

Olfactory adult stem cells have been successfully grown by Prof. Alan Mackay-Sim, deputy director of Griffith University’s new Institute for Cellular and Molecular Therapies in Brisbane, Queensland, Australia. He was awarded Queenslander of the Year in 2003 for his work. His team successfully grew adult stem cells harvested from the human nose, and was published in the journal Developmental Dynamics. The Courier-Mail cited him as follows (22 March 2005, p. 4):

Adult stem cells isolated from the olfactory mucosa (cells lining the inside of the nose involved in the sense of smell) have the ability to develop into many different cell types if they are given the right chemical environment.
 
These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need to stem cell therapies. ...
 
Adult olfactory stem cells are readily obtained from the nose and relatively easy to grow and multiply in the lab. In a few weeks we can make plenty of cells for transplantation.

An advantage of adult stem cells is that, since they can be harvested from the patient, potential ethical issues and immunogenic rejection are averted. Although many different kinds of multipotent stem cells have been identified, adult stem cells that could give rise to all cell and tissue types have not yet been found. Adult stem cells are often present in only minute quantities and can therefore be difficult to isolate and purify. There is also limited evidence that they may not have the same capacity to multiply as embryonic stem cells do. Finally, adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in making more DNA copies during the course of a lifetime. However, there are a number of clinically proven adult stem cell successes.

Adult stem cells do appear in "minute quantities" however, these minute in-vivo quantities can be multiplied in-vitro to therapeutic numbers. For example, many patients have received treatment for heart disease using adult stem cells originating in bone marrow. In 2005, technology has become available whereby stem cells can be harvested, differentiated and multiplied from about ˝ pint of one’s own blood.”

Several types of heart disease have been treated in clinical trials and therapy is commercially available. Patients such as Jeannine Lewis and legendary Hawaiian crooner Don Ho have traveled to Thailand to receive stem cell therapy for their heart disease. Dr. Amit Patel of the University of Pittsburgh McGowen Institute for Regenerative Medicine has been one of the leaders in stem cell therapy for heart disease.


About Embryonic Stem Cells

Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of a blastocyst, an early stage embryo (approximately 1 week old in humans) consisting of 50-150 cells. Moreover, they are pluripotent, meaning they are able to grow (i.e. differentiate) into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body as long as they are specified to do so. This characteristic property distinguishes embryonic stem cells from adult stem cells or progenitor cells, the latter two of which only have the capacity to form a limited number of different cell types. Because of their unique combined abilities of unlimited expansion and pluripotency, embryonic stem cells potentially are the ultimate source for regenerative medicine and tissue replacement after injury or disease. To date there is no evidence that any medical treatments have been successfully derived from embryonic stem cell research.

Embryonic stem cells were first derived from mouse embryos in 1981 by two independent research groups (Evans & Kaufman and Martin). The breakthrough in embryonic stem cell research came in November 1998 when a group led by James Thomson at the University of Wisconsin-Madison first developed a technique to isolate and grow the cells derived from human blastocysts. Normally, blastocyst-stage embryos that are left over after successful in vitro fertilization would not be used but be destroyed. Scientists are only allowed to use these discarded blastocysts after assessment by specialized committees that thoroughly check the research goals of these scientists. Of course, scientific research using those blastocysts may be conducted when it contributes to a better understanding of how to generate cells and tissues that can cure a patient's disease or be used to treat severe injuries. Embryonic stem cell researchers are currently attempting to grow the cells in the laboratory (i.e. in culture flasks: "in vitro") beyond the first stages of cell development. It is important to make sure the embryonic stem cells are fully differentiated into the desired cell type (i.e. tissue) before they are transplanted into the patient, as undifferentiated embryonic stem cells may develop into a tumor after transplantation. Further more, scientists are trying to develop techniques to prevent rejection of implanted cells by the patient (i.e. host-versus-graft response).

One of the possibilities to prevent rejection is by creating embryonic stem cell clones that are genetically identical to the patient. This can be achieved by fusing an egg cell, the nucleus (containing the genetic material: DNA) of which is removed, with a patient's cell. The fused cell produced (containing only the DNA of the patient) is allowed to grow to the size of a few tens of cells, and stem cells are then extracted. Because they are genetically compatible with the patient, the patient's immune system will not reject differentiated cells derived from these embryonic stem cells. More commonly, they are obtained for research purposes from uncloned blastocysts, such as those discarded from in vitro fertilization clinics. Such cells might be rejected if transplanted into a patient, as they do not contain identical genetic information. A possible solution for this is to derive as many well-characterized embryonic stem cell lines from different genetic and ethnic backgrounds and use the cell line that is most similar to the patient; treatment can then be tailored to the patient, minimizing the risk of rejection.

A major development in research came in May 2003, when researchers announced that they had successfully used embryonic stem cells to produce human egg cells. These egg cells could potentially be used in turn to produce new stem cells. If research and testing proves that artificially created egg cells could be a viable source for embryonic stem cells, they noted, then this would remove the necessity of starting a new embryonic stem cell line with the destruction of a blastocyst. Thus, the controversy over donating human egg cells and blastocysts could potentially be resolved, though a blastocyst would still be required to start each cycle.

The online edition of Nature Medicine published a study on January 23, 2005 which stated that the human embryonic stem cells available for federally funded research are contaminated with nonhuman molecules from the culture medium used to grow the cells, for example, mouse cells and other animal cells. The nonhuman cell-surface sialic acid can compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.

A study was published in the online edition of Lancet Medical Journal on March 8, 2005 that detailed information about a new stem-cell line which was derived from human embryos under completely cell- and serum-free conditions. This event is significant because exposure of existing human embryonic stem-cell lines to live animal cells and serum risks contamination with pathogens that could lead to human health risks. After more than 6 months of undifferentiated proliferation, these cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem-cell lines. (Lancet Medical Journal)

Recently, in California, researchers have injected embryonic stem cells into mice as they developed in the womb. Upon maturing, it was found that some of the human ESCs had survived and two months after injection, the researchers found that the ESCs had undertaken "the characteristics of mouse cells."  


Spore-Like Cells

Spore-like cells were described first by Vacanti et al. in 2001 (Vacanti, M. P., A. Roy, J. Cortiella, L. Bonassar, and C. A. Vacanti. 2001. (2) Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80:455–60.) They are extremely small (i.e. <5 micrometer). They appear to lie dormant and to be dispersed throughout the parenchyma of virtually every tissue in the body. Being dormant, they survive in extremely low oxygen environments and other hostile conditions, known to be detrimental to mammalian cells, including extremes of temperatures. Spore-like cells remain viable in unrepaired tissue, frozen at −86 °C (using no special preservation techniques) and then thawed, or heated to 85 °C for more than 30 min. This has led researchers to try to revitalize spore-like cells from tissue samples of frozen carcasses deposited in permafrost for decades (frozen walrus meat >100 years old)(mammoth and bison, Alaska 50,000 years old). In vitro, these structures have the capacity to enlarge, develop, and differentiate into cell types expressing characteristics appropriate to the tissue environment from which they were initially isolated. Vacanti et al. believed that these unique cells lie dormant until activated by injury or disease, and that they have the potential to regenerate tissues lost to disease or damage. Because the cell-size of less than 5 micrometers seems rather small as to contain the entire human germ-line genome the authors speculate on the "concept of a minimal genome" for these cells.

   

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Page Updated 05/06/2006