Embryonic Stem Cells
Main concern with embryonic stem cells is related to uncontrolled growth. Embryonic stem cells are cells which tend to grow fast. However, the rapidly growth must be carefully guided by researchers. These stem cells need to be cultivated and directed into specialised cells with great care because the potential for remaining stem cells to grow uncontrolled could be terrible. These uncontrolled stem cells could eventually form tumours. Embryonic stem cells division are subject to errors during cell division that can result in abnormal chromosome forms. Cytogenetics, the study of abnormal chromosomes, has shown that stem cells tend to show the chromosome aberrations. The most frequent change in human embryonic stem cells involves gain of chromosomes 12 or 17, which both are associated with cancer. There is no way to differentiate embryonic stem cells with abnormal chromosomes form and normal stem cells without genetic testing, because both express the same proteins and specifically stem cell markers. Additionally, the presence of chromosome changes does not affect the ability of these cells to different into appropriate cell types. However, most of these divisions lead to cell death, as a result accidents in division, which lead to extra or missing chromosomes.
Some researchers claim normal chromosomes in human embryonic cells after prolonged time in culture, even after 100 passages. Others have reported recurrent aberrations involving chromosomes 12 and 17 occurring between passages 25 and 45. Despite optimal culture techniques, the genetic integrity of embryonic stem cells is difficult to keep, because of the stresses of tissue culture and the other pressures exerted on the cells after cultures have been frozen and thawed. Cryopreserved embryonic stem cells tend to grow poorly after thawing. Some cells with a growth rate resulting from an extra chromosome 12 or 17 can increase in number and eventually overgrow the normal cells.
Adult Stem Cells
Unlike embryonic stem cells, which can give rise to any lineage, adult stem cells can only generate cells of a specific lineage. Adult stem cells are present in specialized tissues throughout the body, such as bone marrow or skin, and are capable of unlimited production of differentiated cells. For adult stem cells to be able to divide continuously, they must have an active telomerase gene, which is characteristic of all embryonic stem cells. The presence of the telomerase gene enables stem cells to maintain the integrity of the chromosomes throughout many cell divisions, whereas differentiated cells of the body do not have this gene and therefore can undergo only a limited number of divisions. There is a general belief that cancer cells derive from mutated adult stem cells because differentiated cells have a limited life-span and therefore cannot accumulate the necessary mutations for malignant transformation.
Most mutations in adult stem cells that give rise to cancer or leukemia tend to be lineage specific because certain changes will promote growth in one tissue, but not another. Chronic myeloid leukemia is example. Chronic myeloid leukemia is caused by specific chromosome mutations in a bone marrow stem cell. The normal stem cells in the bone marrow divide only when more blood cells are needed, and they become quiet as a result of continuous blood cell production by the mutated stem cells. This enables the abnormal stem cells populating the bone marrow to divide continuously. The mutation in chronic myeloid leukemia includes specific mutations between chromosomes 9 and 22, but this chromosome aberration has no effect in any other tissue because chromosome changes associated with cancer are lineage specific.
The fact that cultured adult stem cells can undergo tissue-specific chromosome changes associated with malignant diseases emphasizes the need to ensure that any adult stem cells used therapeutically, including reprogrammed cells, be monitored for genetic changes.
Scientists have tried embryonic stem cell transplantation in animal experimental models for stroke. Undifferentiated embryonic stem cells that were transplanted into the rat brain, migrated to the damaged area and differentiated into neurons along the border of the lesion. When the same cell line was transplanted into the mouse brain, the embryonic cells did not migrate but remained in one area to produce malignant carcinomas. Embryonic stem cells were undifferentiated or pre-differentiated in vitro to neural progenitor cells.
Mouse embryonic stem cells can differentiate into liver cells in culture. When mice were injected in the spleen with 9 day old cultures, the cells migrated to the liver and generated liver cells. However, when 9 day old and 15 day old cell cultures were injected directly into the mouse liver, there was a high incidence of tumor formation. The authors conclude that even in 15 day old cultures, undifferentiated embryonic stem cells can persist that are capable of forming tumors when transplanted.
Scientists still do not know so much about how stem cell differentiation is controlled. Further research will explain how cell signals operate to trigger cell differentiation. Current stem cell treatments may eventually become routine and regular therapies for serious disease. However, it's important that the safety of these therapies is evaluated and that caution is displayed before a therapy becomes accepted for use. This will allow full benefits of stem cell therapies for everyone.