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The Power of Stem Cells

Ashraf Amlani - Saturday, April 30, 2011

In 1968, two siblings with severe combined immunodeficiency were successfully treated with bone marrow transplant, which is known to contain stem cells. Ten years later, haematopoietic stem cells were first discovered in human cord blood. Previously, embryonic stem cells have been shown to improve the movements of paralysed rats due to spinal cord injuries. However, it was not until October 2010 that the US Food and Drug Administration approved the first clinical trial using human embryonic stem cells to investigate the use of stem cells for spinal cord injury and ensure that stem cells pose no harm to patients. In the FDA approved study, the stem cells were coaxed to become nerve cells then injected into the spinal cord of injured patients. The results of this novel study will determine whether the beneficial effects of embryonic stem cells can be further investigated in humans.

Sources of stem cellsBreak throughs and clinical applications in umbilical cord blood and human embryonic stem cells are the subject of much media attention. Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. They possess two unique properties that somatic cells do not have: self-renewal and potency. Its self-renewal characteristic enables stem cells to divide indefinitely while maintaining its undifferentiated state and having the potential to differentiate into specialized cell types depending on the environment. The two main sources of stem cells can be derived from are adult tissue such as bone marrow or liver, and embryos.

Stem cells in the undifferentiated states do not serve any one function. However, they can be instructed to specialize into any desired cell types to serve any functions. This renewable source of replacement cells and tissues can treat diseases such as Alzheimer’s diseases, spinal cord injury, burns, stroke, diabetes and arthritis. For instance, in Type I diabetes, the islet cells in the pancreas that normally produce insulin are destroyed by the patient’s own immune system. Studies indicate that it may be possible to differentiate human embryonic stem cells into these insulin producing cells in cell culture, and then transplant the cells into the pancreas of the patients. In addition, human stem cells could also be used to test new drugs. For example, cancer cell lines are often used to screen potential anti-tumour drugs. In order to compare the efficacy of different drugs, scientists still have to find a better way to control stem cell differentiation more precisely.

In 1998, the researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells and were able to keep the stem cells alive in vitro. Since then, embryonic stem cell (ESC) research has been as controversial an issue as abortion, because it requires the destruction of a human blastocyte, i.e. a 5 day old fertilized egg that would otherwise have a chance to develop into a fully grown human being. More recently, in early 2007, scientists were able to isolate a new type of stem cell from amniotic fluid. This finding is particularly critical because these stem cells could be used as an alternative to the controversial embryonic stem cells.

Another more ethical way to generate stem cells was discovered in June 2007 by Dr. Yamanaka whose team reprogrammed normal skin cells to embryonic state in mice. These are called induced pluripotent stem (iPS) cells. Similar to embryonic stem cells, iPS cells could be expanded indefinitely and differentiated to form various kinds of tissues. A few months later, the technique was replicated in adult human skin cells. Besides skin cell lines, it was demonstrated that this technique could be used to generate patient-specific cell lines. The Terry Fox Laboratory at the BC cancer agency has been evaluating the ability of a human hepatocarcinoma cell line (MEDII) to selectively enhance generation of mesodermal derivatives including hematopoietic cells, from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs).

Despite all the benefits that stem cells could bring to us, there are several problems yet to be resolved. Although embryonic stem cells are versatile and able to differentiate into different types of tissues, this also renders it unstable for clinical use. If stem cells are not fully differentiated prior to use in patients, they can migrate throughout the body and form tumours known as teratomas. For example, spontaneous tumour formation has been observed in rats and mice persistently. More importantly, immune rejection of transplanted cells has been a major obstacle. This could be due to the expression of different histocompatibility complex antigen on donor cells or from the expression of foreign antigens as a result of culturing hESCs in animal products. Although, the use of autologous (cells from the patient) adult stem cells eliminates problems such as mutation and tissue incompatibility, pharmaceutical companies cannot patent these individualized therapies. This individualization requires on-site medical professionals and various instrumentations posing huge cost and leaving generating autologous stem cells an expensive process.

Today, stem cell research has progressed dramatically and multipotent hematopoietic stem cells derived from bone marrow have been used to treat leukemia. In British Columbia, various stem cells research carried out at local companies and institutions have started to show signs of maturity. STEMCELL Technologies Inc. are providing feeder independent medium for incubation of human embryonic stem cells and induced pluripotent stem cells to prevent the problem of immune rejection due to species incompatibility. The Providence Heart and Lung Institute at St. Paul’s hospital has been investigating the use of mesenchymal stem cells as a potential therapeutic intervention for airway epithelial regeneration particularly in asthma. Also, researchers from the Department of Surgery at UBC are investigating the therapeutic potentials of bone marrow- derived mesenchymal stem cells on hepatic cirrhosis. These and other local research projects demonstrate that local biotech companies and academic institutions are looking forward to harness the full power of stem cells.

Written by Christine Tseng





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