Overview

Understanding Stem Cells

Stem cells possess an extraordinary ability to self-renew and transform into diverse cell types within the body during early development and growth phases. Scientists explore various stem cell types, primarily categorized as “pluripotent” stem cells (comprising embryonic stem cells and induced pluripotent stem cells) and nonembryonic or somatic stem cells, commonly referred to as “adult” stem cells. Pluripotent stem cells hold the capacity to differentiate into all adult body cells, while adult stem cells, located in specific tissues or organs, can develop into specialized cell types within those respective structures.

stem cells

Pluripotent Stem Cells

During the blastocyst stage in early mammalian embryos, two distinct cell types exist: cells forming the inner cell mass and those forming the trophectoderm, contributing to the development of the placenta. The inner cell mass eventually gives rise to specialized cells, tissues, and organs throughout the organism’s entire body. Stem cell extraction from the inner cell mass of preimplantation human embryos, pioneered in 1998 based on earlier research with mouse embryos, enabled the cultivation of human embryonic stem cells (hESCs) in laboratory settings. Subsequent breakthroughs in 2006 led researchers to identify conditions that could reprogram some mature human adult cells into a state resembling embryonic stem cells, known as induced pluripotent stem cells (iPSCs).

Adult Stem Cells

Throughout an organism’s lifespan, populations of adult stem cells act as an internal repair system, generating replacements for cells lost due to regular wear and tear, injury, or illness. Adult stem cells have been pinpointed in numerous organs and tissues, often linked with specific anatomical regions. These stem cells may remain dormant (non-dividing) for extended periods until prompted by the body’s demand for additional cells to uphold and mend tissues.

What Exactly are Mesenchymal Stem Cells (MSCs)?

Well, stem cells serve as the fundamental building blocks from which specialized cells in the body originate. Mesenchymal stem cells specifically belong to the category of adult stem cells. They possess unique qualities like self-renewal, immunomodulation, anti-inflammatory traits, as well as signaling and differentiation abilities. These MSCs, short for mesenchymal stem cells, are notable for their capacity to renew themselves by dividing and transforming into various specialized cell types within a particular tissue or organ.

MSCs find extensive application in treating diverse diseases because of their abilities to self-renew, differentiate, reduce inflammation, and modulate the immune system. Both laboratory-based (in-vitro) and living organism-based (in-vivo) studies have contributed significantly to understanding how MSC therapy works, its safety, and effectiveness in clinical use. (3)

As per a study conducted by Crigna et al. in 2018.

“MSCs mainly exert their regenerative effects through paracrine and endocrine modes of action, which include immunomodulatory, anti-inflammatory, mitogenic, anti-apoptotic, anti-oxidative stress, anti-fibrotic, and angiogenic influences.” (1)

Mesenchymal stem cells (MSCs) come from various tissues such as fat, bone marrow, umbilical cord tissue, blood, liver, dental pulp, and skin.
At Cell & Co., we specifically concentrate on MSCs obtained from Wharton’s Jelly of umbilical cord (WJ-UC-MSCs).

Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) (MSC) Therapy

“UC-MSCs are the most primitive type of MSCs, shown by their higher expression of Oct4, Nanog, Sox2, and KLF4 markers.” (1) 

Mesenchymal stem cells derived from umbilical cord tissue can transform into various cell types and boast the highest rate of proliferation among the three sources namely adipose, bone marrow and cord tissue. (2)

UC-MSCs release growth factors, cytokines, and chemokines, enhancing diverse cell repair processes. (4). These actions collectively support the anti-inflammatory and immune-modulating traits of MSCs.

 

Non-invasive Cell Product

Harvesting UC-MSCs doesn’t involve extracting them from the patient directly. Instead, these MSCs come from a portion of a human umbilical cord that’s ethically donated.

UC-MSCs possess a higher capacity for proliferation compared to BMSCs and ASCs, meaning they multiply more efficiently in laboratory conditions, resulting in greater yields of cells. (15)

Research indicates that certain genes linked to cell proliferation (like EGF), the PI3K-NFkB signaling pathway (such as TEK), and neurogenesis (genes like RTN1, NPPB, and NRP2) show upregulation (increase in the number of receptors) in UC-MSCs compared to BM-MSCs. (15)

The image below provides a comparison among UC-MSCs, BMSCs and ADSCs: 

Comparison between UC-MSCs, BMSCs and ADSCs h

Source

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510077/

Treatment of spinal cord injury with mesenchymal stem cells

 

How does MSCs work in the body?

Mesenchymal stem cells exert positive effects by using their abilities in self-renewal, immunomodulation, anti-inflammatory responses, signaling, and differentiation. These MSCs have the unique capability to regenerate by dividing and maturing into various specialized cell types found within specific tissues or organs. Being adult stem cells, MSCs don’t raise ethical concerns as they aren’t derived from embryonic sources.

“The characteristics of presenting no major ethical concerns, having low immunogenicity, and possessing immune modulation functions make MSCs promising candidates for stem cell therapies.” – Jiang, et al. (6)

Stratech Table showcasing immune system balance

Immunomodulation (immune system regulating)

Mesenchymal stem cells (MSCs) have the ability to regulate the immune system. They can trigger an inflammatory response when the immune system is inactive and reduce inflammation when it’s overly active. MSCs can be crucial in preventing the immune system from attacking the body itself, as often seen in various autoimmune conditions. In a study by Bernardo et al. from 2013, it was found that when MSCs encounter enough pro-inflammatory signals (cytokines), they respond by promoting a suppressive immune reaction, reducing inflammation, and supporting tissue balance. (7)

As per a study conducted by Jiang et al. in 2019.
“Depending on the signal types or strength, MSCs secrete cytokines to promote or suppress the immune responses for maintaining the immune balance.”

 

Anti-inflammatory responses (reducing harmful inflammation)

Inflammation is the immune system’s response aimed at shielding the body from external threats and aiding in its healing processes. Yet, when inflammation becomes uncontrolled, it can harm the body. Prolonged dysregulation of the immune system can lead to various autoimmune conditions like Multiple Sclerosis, Type 1 Diabetes, Inflammatory Bowel Disease, or Lupus. (8)

MSCs possess valuable anti-inflammatory properties that contribute significantly to their therapeutic potential.

How MSCs reduce inflammation:

“MSCs sourced from different origins mitigate inflammation by reducing the production of tumor necrosis factor-α (TNF-α) and Interferon-γ (IFN-γ), while increasing secretion of Prostaglandin (PGE2) and Interleukin-6 (IL-6).” (9)

As per a study conducted by Gugjoo et al. in 2020.
“In general, the central role of mesenchymal stem cells (MSCs) in maintaining homeostasis (immuno-modulation and anti-inflammatory activities) occurs by interacting with immune cells and is mediated through cytokines, chemokines, cell surface molecules, and metabolic pathways. MSCs suppress T-cell proliferation, cytokine secretion, and cytotoxicity (9)”

 

Signaling by MSC & Exosomes (secretome and extracellular vesicles)

The regenerative impact of mesenchymal stem cells isn’t solely dependent on their ability to turn into different cell types or replace injured tissues. It’s also influenced by their secretome, which operates through paracrine mechanisms. (5)

The MSC secretome constitutes a collection of bioactive elements released into the body, including cytokines, growth factors, extracellular vesicles, neurotrophins, soluble proteins, lipids, and nucleic acids. (5)

These secreted elements play crucial roles in regulating various bodily processes, gaining attention as potential biomarkers and therapeutic targets for diseases. (10)

In a 2016 study by Arutyunyan et al., it was observed that UC-MSCs exhibit heightened secretion of neurotrophic factors like bFGF, nerve growth factor (NGF), neurotrophin 3 (NT3), neurotrophin 4 (NT4), and glial-derived neurotrophic factor (GDNF) compared to bone marrow-derived (BM-MSCs) and adipose tissue-derived (AT-MSCs). (15)

Moreover, UC-MSCs release notably higher levels of several vital cytokines and hematopoietic growth factors—such as G-CSF, GM-CSF, LIF, IL-1α, IL-6, IL-8, and IL-11—compared to BM-MSCs. This suggests that UC-MSCs might possess more potency compared to other MSC sources.

MSCs’ Homing properties (how MSCs find their way)

A significant advantage of mesenchymal stem cells lies in their ability to navigate to specific areas of concern, owing to their inherent homing capabilities. MSC homing involves these cells exiting the bloodstream and moving toward the site of injury when administered systemically. (11)

As per a 2019 study by Ullah et al., systemic homing is a step-by-step process regulated by specific molecular interactions. “The process of systemic homing involves five distinct steps: (1) tethering and rolling, (2) activation, (3) arrest, (4) transmigration or diapedesis, and (5) migration.”

This process is depicted in the figure below:

DVC MSCs' Homing properties

 

Differentiation (transforming into different cell types)

Mesenchymal stem cells possess the ability to self-renew and transform into various cell types, making them multipotent stem cells. Simply put, these cells can develop into a range of different cell types such as adipose tissue, cartilage, muscle, tendon/ligament, bone, neurons, and hepatocytes. (12)

As outlined in a 2016 study by Almalki et al., the process of MSC differentiation into specific mature cell types is guided by a mix of cytokines, growth factors, extracellular matrix molecules, and transcription factors (TFs). (12)

The contribution of mesenchymal stem cells to tissue regeneration and differentiation is significant. They aid in maintaining the balance and function of tissues, adapting to changes in metabolic or environmental conditions, and repairing damaged tissues. (13)

Summary

A wealth of research delves into the mechanisms governing mesenchymal stem cells (MSCs). Numerous studies highlight their diverse abilities, encompassing self-renewal, immunomodulation, anti-inflammatory responses, signaling, and differentiation properties. These traits make MSCs applicable across various aging-related scenarios for multiple health conditions.

Emerging research hints that mesenchymal stem cells derived from umbilical cord tissue (UC-MSCs) might exhibit higher potency compared to other MSC sources, potentially amplifying their clinical effectiveness. (15)

For further insights into the therapeutic application of UC-MSCs, explore our services. At Cell & Co., we offer an expanded stem cell therapy utilizing UC-MSCs sourced from one of the leading cGMP laboratory in Malaysia. Our therapy covers a spectrum of health conditions all in relations to healthy aging.

 

References: 

  1. Torres Crigna, A., Daniele, C., Gamez, C., Medina Balbuena, S., Pastene, D. O., Nardozi, D., … Bieback, K. (2018, June 15). Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models. Frontiers in medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013716/
  2. Mazini, L., Rochette, L., Amine, M., & Malka, G. (2019, May 22). Regenerative Capacity of Adipose-Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). International journal of molecular  sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566837/
  3. Chu, D.-T., Phuong, T. N. T., Tien, N. L. B., Tran, D. K., Thanh, V. V., Quang, T. L., … Kushekhar, K. (2020, January 21). An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells. International journal of molecular sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037097/
  4. Jin, H. J., Bae, Y. K., Kim, M., Kwon, S.-J., Jeon, H. B., Choi, S. J., Kim, S. W., Yang, Y. S., Oh, W., & Chang, J. W. (2013, September 3). Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. International journal of molecular sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794764/
  5. Liau, L. L., Looi, Q. H., Chia, W. C., Subramaniam, T., Ng, M. H., & Law, J. X. (2020, September 22). Treatment of spinal cord injury with mesenchymal stem cells. Cell &  bioscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510077/
  6. Jiang, W., & Xu, J. (2020, January). Immune modulation by mesenchymal stem cells. Cell proliferation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985662/
  7. Bernardo, M. E., & Fibbe, W. E. (2013). Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation. Cell Stem Cell, 13(4), 392–402. https://doi.org/10.1016/j.stem.2013.09.006
  8. Ryu, J.-S., Jeong, E.-J., Kim, J.-Y., Park, S. J., Ju, W. S., Kim, C.-H., Kim, J.-S., & Choo, Y.-K. (2020, November 7). Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases. International journal of molecular  sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664655/
  9. Gugjoo, M. B., Hussain, S., Amarpal, Shah, R. A., & Dhama, K. (2020). Mesenchymal Stem Cell-Mediated Immuno-Modulatory and Anti- Inflammatory Mechanisms in Immune and Allergic Disorders. Recent patents on inflammation & allergy drug  discovery. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509741/
  10. Stastna, M., & Van Eyk, J. E. (2012, February 1). Investigating the secretome: lessons about the cells that comprise the heart. Circulation. Cardiovascular  genetics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282018/ 
  11. Ullah, M., Liu, D. D., & Thakor, A. S. (2019, May 31). Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. iScience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529790/
  12. Almalki, S. G., & Agrawal, D. K. (2016). Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation; research in biological  diversity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010472/
  13. Grafe, I., Alexander, S., Peterson, J. R., Snider, T. N., Levi, B., Lee, B., & Mishina, Y. (2018, May 1). TGF-β Family Signaling in Mesenchymal Differentiation. Cold Spring Harbor perspectives in  biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932590/
  14. Walker, J. T., Keating, A., & Davies, J. E. (2020, May 28). Stem Cells: Umbilical Cord/Wharton’s Jelly Derived. Cell Engineering and Regeneration. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992171/
  15. Arutyunyan, I., Elchaninov, A., Makarov, A., & Fatkhudinov, T. (2016). Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem cells  international. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019943/