Umbilical Cord Stem Cells and Your Immune System: How Young Cells Can Help Old Cells

How umbilical cord stem cells support the thymus

Our immune system is a crucial defense mechanism in our bodies, safeguarding us against bacteria, viruses, germs, and toxins. It combats infections, aids in healing, and has the remarkable ability to remember different pathogens (agents that cause illness and disease) for future protection.

There are two main parts of the immune system:¹

1. The innate immune system, which is present from birth. It acts as a rapid-response unit, being the first to respond to invaders. This system includes physical barriers such as the skin, the cornea of the eye, and mucous membranes lining the respiratory and gastrointestinal tracts. The innate immune cells are responsible for attacking and killing invading pathogens to protect us against illness and infection.
2. The acquired immune system is developed through exposure to microbes over time. It works in tandem with the innate system to produce specific proteins, known as antibodies. These antibodies are tailored to defend against particular invaders and remain in the body, ready to recognize and combat the same pathogens if they reappear. This system evolves and strengthens as it encounters various microbes and illnesses.

Central to the immune system are lymphocytes, a special type of white blood cell. Lymphocytes, including B-cells and T-cells, play a vital defensive role in the body. B-cells produce antibodies to neutralize pathogens, while T-cells destroy harmful pathogens and regulate the immune response to prevent overactivation.² T-cells originate from the thymus gland, which is an important component in immune system functionality.

What is the thymus

The thymus, a small two-lobed organ located behind the sternum (breastbone), plays a crucial role in the immune system, particularly in the maturation of T-cells. It is a critical component of the lymphatic system, a part of the immune system that maintains fluid balance in the body. The primary function of the thymus is to develop lymphocytes into specialized T-cells, so your body is ready to combat infections and pathogens. Lymphocytes originate in the bone marrow and then migrate to the thymus, where they undergo specialization into T-cells. ³

In addition to its role in the immune system, the thymus is a part of the endocrine system, responsible for hormone production and release. The hormones produced by the thymus are essential for creating T-cells and supporting overall immune function. The thymus is most active during childhood, generating a lifetime supply of T-cells by the time we reach puberty. This dual role in both the lymphatic and endocrine systems underscores the thymus’s importance in maintaining a healthy immune response.3

What happens when we start to age

As we age, our thymus, an essential organ in the immune system, gradually shrinks. This process is known as thymic involution. While it has a minimal impact on healthy individuals, its effects are more pronounced in older adults. ⁴

Thymic involution impairs the thymus’s ability to perform its normal functions, thereby affecting our immune system’s efficiency. Aging alters the thymic microenvironment — the intricate network involving the thymus and its functions. A significant consequence of these changes is a reduced efficiency in producing thymocytes, precursors to T-cells, essential for immune response. The thymus depends on bone marrow progenitor cells to generate T-cells. Progenitor cells are origin cells. Age-related changes in this process can decrease the number of cells reaching the thymus, leading to a reduced count of specialized and mature T-cells. This decrease weakens our body’s ability to fend off pathogens, increasing the risk of serious illnesses and certain diseases. ⁵

Additionally, aging impacts the environment around the thymus, which is critical in its function. The thymus relies on signals from various organs and systems for the differentiation and proliferation of T-cells. Age-related alterations can contribute to thymic involution and diminish immune system effectiveness. This is a key reason why older individuals are more susceptible to serious infections and illnesses.

If the thymus doesn’t function properly, it can have significant effects on the immune system. Here are some potential consequences:

1. Impaired T Cell Development: The primary function of the thymus is to support the maturation of T cells. If the thymus is not functioning well, T cell development may be compromised. T cells are critical for orchestrating the immune response, recognizing and attacking infected or abnormal cells.
2. Weakened Cell-Mediated Immunity: T cells are a key component of cell-mediated immunity. They play a central role in the direct destruction of infected or compromised cells. If the thymus is not functioning optimally, the production of functional T cells may be reduced, leading to a weakened cell-mediated immune response.
3. Increased Susceptibility to Infections: A compromised thymus can result in a decreased number of mature and effective T cells. This can make individuals more susceptible to various infections, as T cells are essential for coordinating the immune response against pathogens.
4. Immune System Disorders: Thymic dysfunction can contribute to the development of immune system disorders. For example, individuals with thymic abnormalities may be at a higher risk of autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues.
5. Decreased Immune Surveillance: T cells are involved in surveillance activities, constantly patrolling the body to identify and eliminate abnormal cells. If the thymus is not functioning properly, the surveillance capabilities of the immune system may be compromised, allowing abnormal cells to proliferate unchecked.
6. Reduced Tolerance: The thymus also plays a role in establishing immune tolerance, preventing the immune system from attacking the body’s own cells. Dysfunction in the thymus may disrupt this process, leading to an increased risk of autoimmune reactions.

To counteract these natural aging processes, researchers and clinicians are exploring ways to support and rejuvenate the thymus. One promising approach is the use of mesenchymal stem cells (MSCs), especially those derived from umbilical cord tissue, to potentially reverse or slow the decline in thymic function.

How UC-MSCs can help

Mesenchymal stem cells (MSCs) stand out as a powerful tool in regenerative medicine due to their abilities to restore and repair cells. They can transform into different cell types (called multipotency), including bone, cartilage, and fat cells and have self-renewal properties allowing them to maintain and replenish their populations over time. ⁶

MSCs are found in three main sources—bone marrow, umbilical cord blood, and adipose tissue. Of these, umbilical cord MSCs (UC-MSCs) seem to be the most effective. They can multiply faster than other MSCs and are critical in tissue repair with their ability to differentiate into the three primary cell layers.⁷

UC-MSCs are non-invasive to collect, present a lower risk of infection, are multipotent, have minimal tumor formation risk, and have low immunogenicity (the likelihood of triggering an immune response).⁸ These factors make them a desirable option for many clinical applications.

How UC-MSCs support thymus health

Research into the health benefits of Umbilical Cord-derived Mesenchymal Stem Cells (UC-MSCs) is expanding, particularly regarding their potential to protect and rejuvenate the aging thymus in older individuals.

A key discovery in this field is the ability of UC-MSCs to prevent the thymus from shrinking, and potentially even restore its size.⁹ In studies using a mouse model to mimic thymus aging, it was observed that UC-MSC treatment led to an increase in thymus size, making it healthier and larger than before treatment. Remarkably, this treatment also reversed age-related changes in the mice, such as restoring their white hair back to black, akin to younger mice.

Umbilical cord mesenchymal stem cells (UC-MSC) are known for their regenerative and immunomodulatory properties. Especially being able to differentiate into different cell types and send chemical messengers to surrounding cells to improve function and growth. In the context of this study, it seems that UC-MSC have been investigated for their potential to improve the structure and function of the thymus in aged mice.

Here’s some highlights on how these cells might be capable improving thymus function:

1. Downregulation of Aging-Related Genes: The study suggests that UC-MSC may have the ability to downregulate genes associated with aging in the thymus. Aging often leads to changes in gene expression patterns, and downregulating genes related to aging could potentially help in maintaining a more youthful thymic structure and function.
2. Upregulation of Autophagy-Related Genes: Autophagy is a cellular process that involves the degradation and recycling of damaged or dysfunctional cellular components. Upregulating autophagy-related genes suggests that UC-MSC may enhance the thymus’s ability to remove and replace damaged cellular components, promoting cellular health and longevity.
3. Upregulation of Anti-Oxidative Stress-Related Genes: Aging is often associated with increased oxidative stress, which can damage cells and tissues. Upregulating genes related to anti-oxidative stress indicates that UC-MSC may help protect the thymus from the harmful effects of oxidative stress, potentially preserving its function.

This is pretty remarkable as it digs a little deeper into the capabilities of UC-MSCs. UC-MSCs have also been found to counteract aging in thymus epithelial cells, which line various internal and external body surfaces like skin, blood vessels, organs, and glands. When these aging cells were exposed to UC-MSCs, there was a reduction in age-related markers, increased cell multiplication, and go through healthier phases, indicating a rejuvenation effect.¹⁰

Furthermore, UC-MSC treatment has shown promising results in improving thymus function and structure in mice lacking a critical gene for thymus development. These mice exhibited an increase in the number of immune cells and more mature T-cells compared to control groups.¹¹  These findings suggest that UC-MSCs hold significant potential for therapeutic use in cases of thymic dysfunction.

What this all means

The remarkable abilities of UC-MSCs are increasingly appreciated, especially for their potential in rejuvenating the aging thymus. These cells offer regenerative and anti-inflammatory benefits that could counteract age-related thymic decline, critical for maintaining a strong immune system. UC-MSCs’ tissue repair capabilities present a promising approach to address the complex issues of thymic aging. This could be one of the mechanisms to why UC-MSCs are effective in autoimmune conditions, and why they’re held in such high regard for anti-aging/longevity. While we’re still exploring the full range of their clinical uses, current research points towards a hopeful future where UC-MSCs play a key role in revitalizing the aging thymus, enhancing immune function in our later years.

If you’re interested in how UC-MSCs can help your immune system, autoimmune conditions, and/or aging, please contact us to schedule a consultation with one of our physicians at 602.603.3118 or email info@inatehealthcare.org.

References

1. https://www.hopkinsmedicine.org/health/conditions-and-diseases/the-immune-system
2. https://my.clevelandclinic.org/health/body/24630-t-cells
3. https://my.clevelandclinic.org/health/body/23016-thymus
4. Ventevogel, M. S., & Sempowski, G. D. (2013). Thymic rejuvenation and aging. Current opinion in immunology, 25(4), 516–522. https://www.sciencedirect.com/science/article/abs/pii/S0952791513001039
5. Palmer D. B. (2013). The effect of age on thymic function. Frontiers in immunology, 4, 316. https://doi.org/10.3389/fimmu.2013.00316
6. Li, Z., Hu, X., & Zhong, J. F. (2019). Mesenchymal Stem Cells: Characteristics, Function, and Application. Stem cells international, 2019, 8106818. https://doi.org/10.1155/2019/8106818
7. Nishimura, T., Yamaguchi, S., Yoshimura, K., Rubinstein, P., & Takahashi, T. A. (2011). Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. Journal of cellular biochemistry, 112(4), 1206–1218. https://doi.org/10.1002/jcb.23042
8. Nagamura-Inoue, T., & He, H. (2014). Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility. World journal of stem cells, 6(2), 195–202. https://doi.org/10.4252/wjsc.v6.i2.195
9. Pan, X.-H., Lin, Q.-K., Yao, X., Li, Z.-A., Cai, X.-M., Pang, R.-Q., & Ruan, G.-P. (2020). Umbilical cord mesenchymal stem cells protect thymus structure and function in aged C57 mice by downregulating aging-related genes and upregulating autophagy- and anti-oxidative stress-related genes. Aging, 12(17), 16899–16920. https://doi.org/10.18632/aging.103594
10. Yang Zailing, Tian Chuan, Lyu Guanke, Pan Hang, Zhu Xiangqing, Wang Jinxiang, Wang Kai, Ruan Guangping, He Zhixu, Shu Liping, Pan Xinghua. Effect of umbilical cord mesenchymal stem cells on aging thymus epithelial cells. Chinese Journal of Tissue Engineering Research, 2022, 26(24): 3880-3885. https://www.cjter.com/EN/10.12307/2022.570
11. Liu, G., Wang, L., Pang, T., Zhu, D., Xu, Y., Wang, H., Cong, X., & Liu, Y. (2014). Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1(-/-) mice. Cellular & molecular immunology, 11(3), 275–284. https://doi.org/10.1038/cmi.2013.69