Semantron 22 Summer 2022

Stem cell therapies and Alzheimer’s disease

throughout development, from embryonic stages through to adulthood, although their proliferative potential decreases with age. 42 Furthermore, in an AD patient, due to accumulated neuron damage, the proliferative potential declines even more, which makes them not as readily available.

The potential methods we will discuss involve the last two types of stem cells mentioned, iPS and NSCs, as they have the highest likelihood of working as a stem cell treatment.

3.2: Potential stem cell therapies

Exogenous stem cell therapies rely on extraction, in vitro cultivation, and subsequent transplantation of stem cells into regions of the brain affected by AD. These use a patient’s own stem cells and are therefore genetically identical so will not be rejected by the patient’s immune system. With a steril ized syringe, a mixture of healthy neural stem cells can be extracted from the patient. This would most easily be done in the spinal cord. These stem cells are put into a petri dish and can multiply and grow in a culture medium. In approximately seven days, the cell clusters are composed of 10,000 – 100,000 cells. 43 These NSCs can now be delivered to parts of the brain with significant amounts of neuronal loss. After the neural stem cells are implanted and are left to mature, they are still not directly connected to all local circuitries in the brain. Nonetheless, they are responsive to local neurotransmitters. It takes about 2 months for new-born neurons to reach morphological maturity (the point where they can integrate themselves into the existing neural network in the brain). In rat models, growth factors, such as brain- derived neurotrophic factor are administered, and these enhance neurogenesis (the process whereby neurons and NSCs are made) and promote cell proliferation (ability to divide into genetically identical cells). In many mouse trials, there has been successful implantation of neural stem cells and differentiation into neurons and glial cells. 44 After the transplant, the patient will have to be closely monitored in case of any adverse effects. Since these therapies discussed use stem cells taken from the patient themselves, there is no need for immunosuppressants (drugs that suppress the immune system) to reduce the risk of the transplanted cells attacking other cells in the body. For induced pluripotent stem (iPS) cells, the method for culturing the stem cells is a little different. Culturing iPS cells has been tested most frequently with human skin cells, known as fibroblasts. These adult stem cells are grown in cell culture, free from contamination, and under precise conditions of nutrition, temperature, and humidity for 6 weeks. This is left in nutrient broth, a liquid containing nutrients and amino acids. Specific combinations of regulatory genes are inserted into retroviruses which are then introduced to the culture medium. These retroviruses transport the RNA of the regulatory genes into the nuclei of the adult cells, and the genes are incorporated into the DNA of the cells. Individual fibroblasts begin to form colonies of stem cells, and after a 100-day long period of corticogenesis (the process whereby neurons make synapses, fire electrical impulses and release

42 Alzheimer’s disease: how could stem cells help? n.d. 43 Seung et al. 2013. 44 Ibid.

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