It is the promise of a revolution in therapeutic medicine that has caused the world-wide interest  in stem cells. The implications of having stem cells capable of differentiation to replace dysfunctional tissues or organs is remarkable indeed. Although there are significant challenges to be overcome, the medical therapies which could well result may one day change the face of therapeutic medicine.

The use of stem cells in therapeutics is hardly new: the bone marrow transplant (used to combat leukemia and other serious disorders) was first conducted in 1956 in New York. These therapies involve the use of irradiation to eliminate carcinogenic cells in the patient followed by introduction of replacement cells from the donor's bone marrow.  Although the therapeutic regime is harsh it has had success in a number of cases.

Modern applications of stem cell technologies are diverse, but include many areas of tissue replacement, organ repair, pharmaceutical and genetic testing and countless other opportunities.

Requirements for Stem Cell Therapies

The fundamental challenge with any tissue replacement therapy is the very real risk of rejection.  Current medical science counteracts this by employing donors with the greatest tissue biocompatibility possible, through the use of anti-rejection drugs and various forms of immuno-suppression in the recipient. Stem cell therapies  avoid many of these challenges, but there are still four fundamental requirements which must be met:

1. Proliferation - stem cells must replicate in quantities that make them therapeutically useful for the condition they are treating.
2. Differentiation - stem cells must possess the appropriate level of differentiation in order to produce the required biocompatible cells and tissues.
3. Biocompatibility - stem cells must not illicit an antigenic response from the patient's immune system.
4. Longevity - therapeutic stem cells must survive as long as the cells they are intended to replace.

More detailed examinations of potential stem cell therapeutics are described below.

Tissue Replacement

There is active research examining the potential for using stem cells to repair or replace damaged cardiac (and other) tissues.  Current demand for replacement organs and tissues is far greater than the available supply, creating tremendous interest in the availability of stem cell derived alternatives. Tissue replacement / cell based therapies could offer viable treatments for many conditions: diabetes, Alzheimer's / Parkinson's diseases, spinal cord injury, rheumatoid arthritis stroke, burns, heart disease and many other disorders.

The following conceptual diagram (NIH 2006) outlines the concept of generating replacement cardiac tissue in vitro and then transferring the healthy tissue into the patient.

http://stemcells.nih.gov/StaticResources/images/figure4_sm.jpg

Diabetes

Type I diabetes is an inability of the pancreatic cells to regulate blood sugar levels through insulin. A medical therapy based on replacing a patient's cells with stem cell derived from tissue culture would have immediate demand world-wide, perhaps one day eliminating the need for daily insulin injections

http://stemcells.nih.gov/StaticResources/info/scireport/images/figure72.jpg

Parkinson's Disease

Parkinson's disease is a degenerative disorder in which the individual loses nerve cells in the brain. Stem cell therapeutic experiments have shown potential for reversing this otherwise untreatable disorder. One individual (male, in his 50's) who suffered from progressive Parkinson's and had not responded to other therapies was the subject of stem cell therapy commencing in 1999. 

Stem cells were sampled via biopsy from the patients brain and grown in vitro. This yielded approximately 20% viable, dopamine-producing neural cells which were re-injected into the patient's brain.

Tremors in his hands diminished and a year later he had improved by 83 % (UPD Rating Scale) despite taking no other medications.  For those suffering from this disease, this new hope is promising indeed.

Multiple Sclerosis

Dr. Harry Atkins, at Ottawa's Centre for Stem Cell Research has been applying stem cell technology to combat MS in Canadian patients. His technique involves treating the patients blood (to remove stem cells) and then involves an intense round of chemotherapy (10 days) to deactivate the patient's immune functions. After this the blood stem cells are re-transplanted to repair the immune system (20 days).

Atkins et al have treated and Freedman have treated 13 patients with this with this method. The outcome: one fatality due to the chemotherapy and 12 patients with no symptoms of MS once again living normal lives.

SCNT (Stem Cell Nuclear Transfer)

SCNT (stem cell nuclear transfer) is a technique for creating pluripotent stem cells. The patient provides a somatic (adult) stem cell which is used to fertilize a donor egg to create a biocompatible line of stem cells from the blastocyst with an inner cell that has unlimited replication and differentiation capabilities. Effectively the egg is now genetically directed by the implanted nucleus from the adult somatic cell. SCNT-derived tissues will not suffer from immune system rejection and have many realistic medical applications undergoing development. Furthermore, SCNT may counter many of the arguments put forth by the anti-stem cell lobbyists since it requires no fetal tissues.

http://www.molbio.princeton.edu/courses/mb427/2001/projects/09/transfertutorial.htm

SCNT is currently legal for research purposes in the Britain (Human Fertilization and Embryology Act) but is significantly controversial in the United States where there is variable state legislation.

Groups currently working on SCNT technology include:

	Human Fertilization and Embryology Authority (UK)
	Newcastle Centre for Life (UK)
	Harvard University (US)
	University of California San Francisco (US)

SCNT will continue to be studied and developed as it holds exceptional potential for medical therapeutics.

Transplantation Breakthrough - Dead Heart Revived

Researchers at the University of Minnesota (January 2008) have reported reviving a "dead" heart by re-populating it using stem cells. This stunning research involved removing internal cells from a dead rat heart and leaving a hollow shell of the heart. Following the introduction of heart / stem cells from a healthy rat into the dead heart tissues the researchers waited several days. During this period the newly-introduced cells fleshed out the tissue to original proportions. The researchers were absolutely stunned when the heart began beating again.

"We've taken organs from cadavers, removed all the cells, put cells back in and been able to reanimate what was previously a dead organ," said molecular biologist Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota.

"What that means, we hope, is that one day if you need a new organ we'll be able to take your cells, transplant them into this framework or scaffold and build you an organ that works for you," she said from Minneapolis-St. Paul.

The great hope is that this opens the door to the future creation of bio-artificial organs that are a perfect match for the recipient. The concept is significant indeed: organs and tissues built to replace diseased components on demand. Interesting indeed.

Tissue Type Alteration (2008)

There has been success reported out of Pennsylvania University where scientists (John Gearhart et al) have induced cell type alterations via a "genetic switch" (Nature 2008). This work is of particular significance since it was conducted on living mice, rather than in vitro.  The technique employs a viral vector which incorporates the DNA essential for the cellular alteration. In their research the group injected three genes to promote insulin production into the pancreatic  cells of living mice.  The viral particles delivered the genes and three days later some of the affected cells began secreting insulin. This viral vector system may in fact actually replace the use of embryonic stem cells since induction of  selected cellular characteristics may soon be possible for a growing range of cell types.

Embryonic stem cell differentiation.

First Manitoban Adult Receives Stem Cells (2009)

A few mL of "Cord Blood" (umbilical cord blood) are being used to treat a potentially deadly blood condition in an adult Manitoba patient. This is expectedly to provide a 50% chance of recovery  for a patient who is gravely ill.  Prior stem cell treatments in Manitoba have occurred with children, to combat childhood leukemia - this is the first application for an adult in the province.  The use of stem cells allows treatment of immuno-disorders, leukemia and  biochemical diseases.

The treatment involves deactivating the patient's own immune system via radiation and chemotherapy before using the stem cells to minimize the risk of rejection.

Although Canada does have a national Core Blood Bank, Manitoba currently does not and must import stem cells for therapeutics.

U.S. Clinical Trials Commence (2009)

The U.S. Food and Drug Administration has permitted a company based in California to begin clinical trials (human testing) using embryonic stem cells. The company (Geron) is slated to begin clinical testing on spinal cord patients to mimic successful results in lab tests. The potential benefits could be highly significant.

http://www.geron.com/products/