From IJMCM
A Diagram Summarizing the Medical Benefits of Stem Cells
Introduction Stem cell therapy is a type of disease treatment involving the injection of regenerative cells into the body that help promote the healing and recovery of tissues. In the case of addiction treatment, this experimental neuroengineering technique can be used to repair neuron damage within the brain. Bone Marrow-Derived Mesenchymal Stem Cells This article will focus on bone marrow-derived mesenchymal stem cells, or BM-MSCs, as they have demonstrated promising therapeutic potential to treat addiction-induced hippocampal damage. To provide context and review content from past units, addiction-induced hippocampal damage is caused by excitotoxic substances. These substances overstimulate glutamate receptors within the hippocampus to such a severe extent that neuronal function is damaged and widespread cell death occurs. This translates to impairments in cognitive function on the outside. The restorative capability of mesenchymal stem cells is attributed to various characteristics. First, mesenchymal stem cells can differentiate into glial and neuron-like cells, making them compatible with other neurons in the brain. Second, mesenchymal stem cells can secrete a multitude of beneficial growth factors, being BDNF, GDNF, and bFGF. BDNF, or brain derived neurotrophic factor is a protein which maintains and helps nerve cells grow and differentiate. GDNF, or glial cell line-derived neurotrophic factor promotes neuronal commitment and enhances axonal growth. Lastly, bFGF or basic fibroblast growth factor promotes the proliferation and differentiation of neuro-progenitor cells in the hippocampus. Mesenchymal stem cells can also secrete micro vesicles and exosomes, which are microscopic sacs that contain mRNAs capable of mediating cell communication with other neurons and astrocytes. Exosomes in partially can foster the growth of neurites –projections from the cell body that eventually develop into dendrites and axons –through the delivery of miRNA, microRNA, to neural cells. There have been numerous applications of mesenchymal stem cells to animal models with many positive results observed. These include reduced substance intake and cravings, improved cognitive function, and an increase in beneficial neurotrophic factors. Limitations The main limitation of mesenchymal stem cells is their sub-optimal homing ability, as less than 10% of mesenchymal cells manage to reach a target tissue. A stem cell’s homing ability is defined as their capability of finding the right migration destination following injection. Currently, mesenchymal stem cells have extremely inefficient homing abilities due to two potential reasons. First, mesenchymal stem cells get trapped within lung capillaries following injection. Second, the expression of molecules that guide mesenchymal stem cells during their migration efforts, such as CXCR4, decrease throughout the homing process which subsequently cause stem cells to travel off course. However, with the assistance of nanotechnology, mesenchymal stems cells could more consistently travel to the granular cell layer within the dentate gyrus, a region within the hippocampus that is prominently damaged from addiction and employ their regenerative effects. Biomedical-Based Solutions Three-dimensional nanotechnology simulation will enable scientists to understand what prevents the stem cells from getting trapped in the blood vessels, and by using biomimicry, scientists will fabricate nanostructures capable of avoiding this fate. These nanostructures will also be used to modify the anatomy of mesenchymal stem cells, enabling them to increase production of the CXCR4 molecule to guide them during their homing process. An investigation to test the effectiveness of nanostructure technology would proceed as follows: researchers aided by AI would come up with certain nanostructures that they believe would have the most optimal assistive effects when combined with mesenchymal stem cells. They would then use a highly advanced computational biology model to test how this nanostructure would interact with the stem cell itself. Data would be produced describing increase or decrease in effectiveness in targeting, possibility for toxicity, ease of mass production and integration with the stem cell, and general complexity.
Key Vocabulary
Excitotoxicity - Toxic behavior of excitatory neurotransmitters like glutamate that lead to loss of neuronal function and eventually cell death; when too much glutamate is released within the brain, nerve cells become overexcited and eventually damaged.
Glutamate - The most common excitatory (promoting activity) chemical neurotransmitter within the brain that plays a role in supporting proper brain function. However, it must be maintained at a healthy concentration; too much or too little glutamate can cause damage to the brain.
Cognitive Function - The ability to use the brain to complete thinking and learning tasks
References
“BDNF Gene.” MedlinePlus Genetics, 1 Mar. 2013, medlineplus.gov/genetics/gene/bdnf.
Cortés, Daniel, et al. “The Non-Survival Effects of Glial Cell Line-Derived Neurotrophic
Factor on Neural Cells.” Frontiers, 22 Aug. 2017,
“Glutamate.” Cleveland Clinic, my.clevelandclinic.org/health/articles/22839-glutamate.
Gould, Thomas J. “Addiction and cognition.” Addiction science & clinical practice vol. 5,2 (2010): 4-14.
Rafaiee, Raheleh, and Naghmeh Ahmadiankia. “Bone Marrow Derived Mesenchymal Stem Cells in Addiction Related Hippocampal Damages.” International journal of molecular and cellular medicine vol. 7,2 (2018): 69-79. doi:10.22088/IJMCM.BUMS.7.2.69
Sun, Dong et al. “Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury.” Experimental neurology vol. 216,1 (2009): 56-65. doi:10.1016/j.expneurol.2008.11.011
Ullah, Mujib et al. “Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement.” iScience vol. 15 (2019): 421-438. doi:10.1016/j.isci.2019.05.004
Disclaimer: This information is intended for educational use only, and should not be construed as professional advice.