Monday, November 21, 2011

The History & Future of Stem Cell Research


What are stem cells?

Stem cells occupy the bodies of mammals of all species, ages and sizes. Stem cells provide every cell, organ and tissue in the body with a foundation. The stem cells that remain in the body after it is formed and fully developed have exceptionally long lives in which they self-replicate and self-sustain to contribute to the normal regeneration needed in the body. In development, they are blank until programmed with a specialized function, such as producing a spleen or a heart, or building a skeletal system (“Questions and answers,” 2011). Embryonic stem cells are those found in the tissues of an embryo and all of the organs produced for healthy gestation. There are three types of “adult” stem cells, hematopoietic stem cells, which form blood, endothelial stem cells, which form the vascular system, and mesenchymal stem cells which form muscle, fibroblasts, bone, cartilage and fat (“Questions and answers,” 2011). Additionally there are pluripotent and multi-potent stem cells, the difference between which, being that pluripotent has a specialized function with regenerative qualities and multi-potent cells have the ability to differentiate, or become one of several tissues or organs (“Questions and answers, 2011).

Embryonic Stem Cells:

Embryonic stem cells (ESCs) possess a greater rate of regeneration and replication, they are considered to be more plastic than “adult” stem cells because of their natural effectiveness, considering that these are the cells responsible for composing an entire human body in around nine months. ESCs can be found in the blastocyst that is the product of the first week of conception (“Questions and answers,” 2011). Samples of this type are achieved through left over compositions of in-vitro fertilization (Green, 2001), although ESCs can also be found in amniotic fluid, baby teeth and umbilical cord blood through donors (“Questions and answers, 2011).

Hematopoietic Stem Cells:

Due to the extensive research on hematopoietic stem cells (HSCs), we know much more about them than any other “adult,” human stem cell. HSCs are the regenerative tissue of the circulatory and immune system, making them invaluable to modern medicine. HSCs have the capability to become any type of blood cell, based on research. These wonderfully malleable cells thrive for extended periods in bone marrow, and periodically circulate in the blood stream, dividing into progenitor cells, precursors to specialized cells. When all functions of HSC circulation are complete, the HSC regenerate, some complete the process of apoptosis (programmed cell death) and the rest return to the bone marrow. What separates the cells that preform apoptosis versus those who do not is currently a research unknown (“Hematopoietic Stem Cells,” 2011).

Why study stem cells?

In the scientific community the pursuit to understand the human body is an endless one. Every type of cell serves some purpose. The more the functions of human cells are understood, the more possibilities unfold for preventative and treatment measures for the many things that can go wrong within the body. The short answer is the medical benefits that stem cells can provide those in need.

A brief history of stem cell research:

In 1945 scientists were researching mice that were exposed to lethal doses of radiation. It was suspected that bone marrow possessed that ability to form new blood cells. The proof arose when scientists effectively preserved the poisoned mice by transplanting bone marrow from healthy mice. In 1985, a scientist by the name of Perkins did some research on the embryonic stem cells of mice. It was determined that all progenitor cells could be produced between mouse ESCs and hematopoietic growth factors, which cause hematopoiesis or the formation of all the blood cells within the body (“Hematopoietic stem cells,” 2011).
In the 1960’s, scientists Til and McCullough discovered regenerative qualities and plastic capabilities while analyzing bone marrow. In 1992, when the plasticity of HSCs and ESCs was still an uncertainty, the New York Blood Center began storing umbilical cord blood and placenta that would otherwise be discarded to begin research on human ESCs (“Hematopoietic stem cells,” 2011). In 1998 research teams in Johns Hopkins University and the University of Wisconsin, Madison successfully grew human stem cells in culture. Their efforts included the use of telomerase to prevent death of the cell line, easing the burden of time for further research, the result; “an immortal, pluripotent human stem cell culture (Green, 2011).”
Former President Bill Clinton had aspirations to fund stem cell research during his presidency, however, his term ended and with the arrival of George W. Bush in office, research was severely limited. In 2001 Bush limited funding to research on currently established ESC lines only, and vetoed against expansion of research for two years, consecutively (Townsend, 2008), despite Kerry’s campaign for funding new cell lines in the election of 2004 (Sharockman, 2010). In 2005 Korea allowed for the cloning of embryos with the intent of extracting cells for research. Here, began the pursuit of the scientific community in the U.S. and Japan to catch up (Sabin, 2005), followed by Israel, England and Australia (Lu, 2009). President Barack Obama favored the expansion of stem cell research as a senator and opened funding to research on new ESC lines in 2008 upon being appointed president (Lu, 2009).
Current treatments and practices involving HSC and ESC
HSC is currently being stored for some cancer patients, as a finalized treatment, while they undergo chemotherapy and take other cancer treatment drugs. Upon cleansing the body of cancerous cells, HSCs from the patient are reintroduced to promote healthy regeneration, division and apoptosis of the many cells in the blood (“Hematopoietic stem cells,” 2011).
Similarly, bone marrow is transplanted from match donors to promote hematopoiesis after chemotherapy in those being treated for leukemia and lymphoma. An alternative treatment to bone marrow transplant, Gleevec, was introduced in 2001 as a means to encourage apoptosis in infected white blood cells. Results of clinical trials for Gleevec are currently an unknown (“Hematopoietic stem cells,” 2011).
Bone marrow transplants can have a positive impact in many inherited blood disorders, such as sickle-cell anemia, osteoporosis, and Hunter’s syndrome. Treatments for muscular dystrophy are also currently in clinical trials (“Hematopoietic stem cells,” 2011).

Challenges for stem cell research:
Challenges for the researcher:

There is one hematopoietic stem cell to every ten to fifteen thousand (1/10,000-15,000) bone marrow cells and to every hundred thousand blood cells in circulation of the circulatory system (“Hematopoietic stem cells,” 2011). There is no current efficient method of distinguishing between “adult” hematopoietic stem cells and other blood cells, therefore identifying them can be incredibly difficult. To add an element of challenge, without host, cells do not continue to regenerate and divide for long. Proliferation, or continuing the life of a cell outside of a host, can more easily be achieved, however, if a method of identification became available (“Hematopoietic stem cells,” 2011).
Challenges for the research:
As previously mentioned, funding has not always been readily available in the U.S. for all forms of stem cell research necessary to advance the way the scientific community aspires to in medicine. Embryonic stem cells are best extracted from destroying an embryo, which raises moral and ethical question, particularly among religious groups and those affiliated. That affiliation is likely the reason for Bush’s 2001 bill as well as his multiple vetoes against opening funds for new embryonic stem cell lines.
In matters involving conception, gestation and early development, the public is often divided. While a zygote and embryo are not a person, they are the precursor to a person and to many religious institutions, the destruction of them is wrong. Incidentally, the embryos and other tissues currently being used for ESC research are tissues that would otherwise be discarded in waste; such is the case with in vitro fertilization “left-overs” and umbilical cord blood and placenta (Green, 2011).
Federal funding is no longer a concern under the Obama administration, although, due to economic decline, much funding, outside of what is provided by the federal government is in jeopardy (Lu, 2009). In addition, the fifteen years of debate surrounding the funding of stem cell research may have cost the U.S. an entire generation of scientists who may have dedicated their career to studying stem cells, according to the co-director and co-founder of the Harvard Stem Cell Institute, David Scadden, whose research involves mainly hematopoietic stem cells (Calborn, 2011).

Challenges in “cell-therapy:”

“Cell therapy” is the term for the use of stem cells to replace damaged cells with healthy cells. Identification of HSCs also presents a problem with treatment, as well as the availability of enough HSCs at a time to be effective (“Questions and answers,” 2011). Researchers have been able to extract HSCs from bone marrow in a donor using Granulocyte Colony Stimulating Factors (GCSF). The blood is filtered through a machine that catches CD34+ cells, or cobblestone area-forming cells, and then returns red blood cells. This yields a five to 20% concentration of “true hematopoietic stem cells (“Hematopoietic stem cells,” 2011).”
ESCs also present problems that cannot be ignored within the realm of “cell therapy” treatment. First, as with conception, the conditions of integration must be immaculate for the therapy to be successful (“Hematopoietic stem cells,” 2011). White blood cells fight off foreign cells, for they are designed to determine the difference between self and non-self. This is the cause when the body rejects transplanted tissue (Alters & Alters, 2008). T lymphocytes, a specialized white blood cell that has the capability to differentiate as well, are great for integrating EBCs and fighting off infection, however, they are also the cause for graft-versus-host disease. In order to properly integrate, immune-suppression therapy need take place, which is a dangerous endeavor (“Hematopoietic stem cells,” 2011).

The future of stem cell research:

[Extracting stem cells from a patient]. . . That can become the ultimate, personalized medicine tool kit: a stem cell-based tool kit to study what goes wrong, determine what drug candidates might affect it, and possibly even supply the cells to replenish those lost in the disease.
– David Scadden (Clalborn, 2010)
Stem cell research, as it progresses over the next decade or more, will be exploring the plasticity of stem cells and the possibility of using them to grow whole organs, tissues and cure degenerative diseases such as muscular dystrophy and Parkinson’s disease (“Questions and answers,” 2011).
Stem cells found in the brain are almost completely inactive, they barely respond to injury or disease. The use of ESCs to treat mental illness or brain injuries is a real possibility in the future, due to the current support from the federal government (“Questions and answers,” 2011).

In summary:



Should the next president continue funding of ESC research, an assay for identification and/or solution of proliferation become available to scientist and the economy make a full recovery, there will still be challenges ahead for stem cell researchers. For every question answered is bound to inspire even more questions.
As with any research and development of medical treatment, morals and ethics must play a role in regulation and law. People must be protected, donors must be protected and rights must be protected. Conforming to the proper guidelines, the results of stem cell research are seemingly endless. It is with bated breath that the families of fatally ill and mortally wounded patients wait for an answer to their prayers. Stem cell research could quite possibly be that answer.

References:

Alters & Alters (2008) Biology: Understanding Life. Hoboken, NJ.

Clalborn, K. (2011). Federal funding for stem cell research: 15 years of indecision. The Journal of Clinical Investigation, 121(7), 2531.

Green, R. (2001). The stem-cell debate. Retrieved from http://www.pbs.org/wgbh/nova/miracle/stemcells.html

Hematopoietic stem cells. In Stem cell information [world wide web site]. Bethesda, MD: National
Institutes of Health. U.S. Department of Health and Human Services. (2011) [cited Wednesday, November 16, 2011] Available at http://stemcells.nih.gov/info/scireport/chapter5

Lempien, E. (2011, July 28). AAAS welcomes court ruling to allow continued federal funding of
embryonic stem cell research. Retrieved from http://www.aaas.org/news/releases/2011/0728stem_cell.shtml

Lu, A. (2009, March 04). Budget cuts endanger stem-cell research in NJ. The Philadelphia Inquirer, p. A1.

Questions and answers about stem cells. (2011). Retrieved from
http://www.aaas.org/news/press_room/stemcell/faq.shtml

Sabin, B. (2005). Stem cell research-who benefits? who loses?. J@pan Inc, (64), 3.

Sharockman, A. (2010, June 11). Bill mccollum and barack obama see eye-to-eye on stem cell research, rick scott claims. St. Petersburg Times.

Stem cell information [world wide web site]. Bethesda, MD: National Institutes of Health. U.S.
Department of Health and Human Services. (2011) [cited Wednesday, November 16, 2011] Available at http://stemcells.nih.gov/info/health

Townsend, T. (2008, September 26). Mccain stem cell ad irks conservative christians ad never uses the term 'embryonic,' which is at the heart of dispute about stem cells in missouri. St. Louis Post-Dispatch, p. C1.

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