Mesenchymal stem cells (MSCs) are being used in a new form of tissue-regeneration therapy that could save or improve the lives of many patients. This paper specifically focuses on the development of liver regeneration therapy in mice using MSCs, which could then hopefully be deployed in human applications. Liver transplants,the most common treatment for liver failure, do not address the needs of the patients on the ever-growing waiting lists for a correct match.
Mesenchymal Stem Cells: Regenerative Medicine at its best.
Mesenchymal stem cells (MSCs): Regenerating the liver
One of the most promising and life-saving therapies being developed today is the use of mesenchymal stem cells (MSCs) to regenerate human tissue. As in the case of all stem cells, MSCs have a unique therapeutic potential to repair tissue because they are both multi-potent yet are highly capable of self-renewal ("MSCs," R&D Systems, 2013). They are primarily found in bone marrow but have also been isolated from other parts of the body, including the blood of the fetus' umbilical cord blood, liver and lung tissue ("MSCs," R&D Systems, 2013). MSCs can be grown so they regenerate into many different cell types, making them extremely flexible and for use in medical therapies ("MSCs," R&D Systems, 2013).
One example of a therapy deploying the flexibility of MCSs to great effect is a developing treatment for liver failure, currently being tested upon mice. MCSs were used to create liver 'buds.' These transplanted buds, when transplanted in the mice, worked in conjunction with the mice's other organs and secreted human liver-specific proteins. "They also created human metabolites, tiny molecules that are produced when the body metabolizes a substance" ("Researchers create miniature human liver out of stem cells," CBS, 2013). Liver failure has resulted in a transplant waiting list of more than 16,500 on an annual basis but only 6,256 people were able to receive a liver transplant in 2012. The hope is that these buds could be used to repair and restore the function of human livers ("Researchers create miniature human liver out of stem cells," CBS, 2013).
After being transplanted, the liver cells in the experiment grew new blood vessels, evidently regenerating themselves. "We just simply mixed three cell types and found that they unexpectedly self-organize to form a three-dimensional liver bud… After hundreds of trials, the three cells worked together and began to make three-dimensional structures" said the Japanese scientists who conducted the study ("Researchers create miniature human liver out of stem cells," CBS, 2013). The buds were implanted in the mice's brains but this would not be used in the human application of the therapy. The ideal would be to "mass-produce' human liver buds from induced stem cells for a scaled-up transplant attempt on a human patient" (Vergano 2013).
To construct an preliminary experiment determining the efficacy of this therapy would require a comparison of two groups of mice, all of which had induced liver failure (the liver failure in the mice of the original experiment was chemically induced): one of the groups would receive the treatment and the others would not, and the experimental group would be monitored for tissue regeneration (Vergano 2013). If the experimental group showed significant improvement compared with the control group, this would establish that the therapy had some validity. The observable positive result supporting the therapy would be revascularization of the liver in the experimental group vs. A failure of the liver to show improvement in the experimental group when compared with the control group. However, there would also need to be an extended period of longitudinal analysis of the effects of the therapy on the experimental group mice's health to see if the improvement continued and did not produce damaging side effects.
The MSCs in the liver therapy are not derived from human embryos and thus the objections to discarding human embryos are not a factor in the ethical discussion about the therapy. In fact, "the number of MSCs that can be obtained from a donor is significantly lower than the number needed for tissue regeneration. Therefore, MSCs are expanded ex-vivo in media supplemented with growth factors" and created in a lab ("MSC growth factors," R&D Systems, 2013). The main ethical objections to the use of MCSs revolve around the question of scientists' right to create new organs and the possible risks involved. The Japanese research team "relied on a 'cocktail' of so-called induced stem cells grown to resemble the nascent liver bud cells used in the experiment" (Vergano 2013). The mice in the experiment must be closely monitored to see if they develop liver tumors, one of the possible negative side effects of the therapy. "Concerns linger about cancer risks from stem cells implanted into patients. The liver buds also lacked immune cells that filter toxins from the bloodstream and structural cells that send digestive enzymes into the gut from a real liver" (Vergano 2013). Other objections which might arise are the fact that liver transplants are effective, proven therapies while this therapy is not.
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