Embryonic Stem Cells
In 1998, the first human embryonic stem cell (hESC) line was created from a fertilized egg. This was a significant milestone in regenerative medicine because hESCs are pluripotent, meaning they can become any cell in the body, and stem cells could conceivably be grown and differentiated into replacement cells for any applicable therapeutic need. However, the seemingly unlimited therapeutic potential associated with hESCs were tempered with safety and ethical issues. Specifically, because of the limited population source from which hESCs are derived, potential patients would be exposed to similar immune rejection risks as those of organ transplant recipients when receiving organs from donors of not identical genetic matches. Moreover, hESC recipients would face increased risks to cancer or other potentially unknown epigenetic diseases of the donor. Accordingly, the ability to generate patient-specific replacement cells with pluripotent capabilities became the next sought after milestone to fully realize the therapeutic potential of regenerative medicine.
NUCLEAR TRANSFER
A schematic of nuclear transfer, a previously explored technique to generate genetically matched stem cells.
Scientists tried to address this hurdle with a technique that replaces an egg cell’s nucleus with the nucleus from a patient’s skin cell (See Figure). Since the nucleus of an adult skin cell has a full set of chromosomes, the egg cell would in a sense be fertilized with an exact copy of the patient’s DNA. The embryonic stem cell line derived from this “fertilized” egg cell would be a genetic match to the patient and likely to not be rejected. However, this technique was highly inefficient and relied on donated egg cells, which are from a limited population source and difficult to obtain.
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