Types of mesenchymal stem cells and their mechanisms of аction – BioAge
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Types of mesenchymal stem cells and their mechanisms of аction

Mesenchymal stem cells (MSCs) are one of the most studied cell types for regenerative stem cell therapy. This is due to their diverse capabilities, which can lead to promising results in a wide variety of conditions. This article describes the three most common sources of mesenchymal stem cells (MSCs), as well as their main mechanisms of action (how they work).
What are mesenchymal stem cells?
Stem cells are body cells, raw materials are cells from which all other cells with specialized functions are created. Mesenchymal stem cells are adult stem cells that have self-renewing, immunomodulatory, anti-inflammatory, signaling and differentiating properties. The ability of mesenchymal stem cells (MSCs) to self-renew is characterized by their ability to divide and develop into a variety of specialized cell types present in a particular tissue or organ.
Mesenchymal stem cells (MSCs) can be obtained from a variety of tissues, including adipose tissue (fat), bone marrow, umbilical cord tissue, blood, liver, dental pulp, and skin.
MSCs are widely used in the treatment of various diseases due to their self-renewing, differentiating, anti-inflammatory and immunomodulatory properties. Studies in vitro (carried out in laboratory conditions) and in vivo (carried out in a living organism) have confirmed the understanding of the mechanisms, safety and efficacy of MSC therapy in clinical applications.
According to a 2018 study by Crigna:
“MSCs mainly exert their regenerative effects through paracrine and endocrine mechanisms of action, which include immunomodulatory, anti-inflammatory, mitogenic, anti-apoptotic, antioxidant, anti-fibrotic and angiogenic effects – influence “.
This article focuses on mesenchymal stem cells derived from adipose tissue (ADSC), bone marrow (BMSC) and umbilical cord tissue (UC-MSC).
MSCs of adipose tissue (ADSC)
MSCs of adipose tissue are obtained from subcutaneous adipose tissue (adipose tissue), they can be quickly obtained in large quantities and with high cellular activity through liposuction. {{1 }} ADSCs will be more viable if obtained from a younger donor. This can be a problem for older patients who are participating in an autologous procedure (using your cells), as older cells may be less suited for the long-term survival of the recipient. MSCs derived from adipose tissue (ADSC) from younger donors have a higher proliferation rate (survival after transplantation) compared to the elderly, but the ability to differentiate persists with age, which offers advantages over mesenchymal bone marrow stem cells (BM -MSC).
However, ADSCs retain their potential to differentiate into cells of mesodermal origin (middle cell layer), and they are widely known for their low immunogenicity and modulating effects. Less than 1% of them expressed the HLA-DR protein on their surface, which led to immunosuppressive effects and made them suitable for clinical use in allogeneic transplantation and therapy for the treatment of resistant immune disorders.
It is widely accepted that ADSC can be used for many different conditions. ADSCs can also be a viable source for most orthopedic procedures. Common uses include spinal cord injury, arthritis, localized joint inflammation, knee pain, and other musculoskeletal problems.
However, clinical use of ADSCs still presents some challenges. These problems include proliferative restrictions on cell age, limited differentiation options, and protocol standardization.
Bone marrow derived MSCs (BM-MSCs)
Bone marrow mesenchymal stem cells (BM-MSCs), which are classified as multipotent adult stem cells, are widely used in the treatment of various diseases due to their self-renewing , differentiated and immunomodulatory properties.
“In vitro and in vivo studies have confirmed understanding of the mechanisms, safety and efficacy of BM-MSC therapy in clinical applications. The number of phase I / II clinical trials is accelerating.; however, they are limited in the size of items, rules and standards for preparing, transporting and administering the BMSC, which leads to inconsistencies in inputs and treatment outcomes. ”
Limitations
Bone marrow harvesting is highly invasive and painful. which requires general anesthesia and several hours of hospitalization. BM-MSCs constitute a rare population, accounting for only 0.002% of the total population of stromal (stem) cells, and their isolation depends on the patient’s condition and the amount of collected matter.
Like ADSCs, the quantity and quality of bone marrow stem cells decrease with age. BM-MSCs are likely to be more viable if obtained from a younger donor using allogeneic (cells come from a third party) treatment.
“Stem cells isolated from the elderly had a low rate of proliferation and differentiation into osteoblasts, while they increased the expression of apoptosis markers and SA-β-gal-positive cells (an indicator of senescence cells)”
Most preclinical and clinical trials have shown promising results for BMSCs in treating a variety of diseases with few side effects during follow-up. BM-MSC therapy is currently used to treat osteoarthritis, neurodegenerative diseases, and sports-related injuries.
Mesenchymal cord tissue stem cells (UC-MSC)
UC-MSC can be obtained from various areas of the umbilical cord and the perivascular area of the umbilical cord. As usual, such tissue, the umbilical cord, contains a rich source of mesenchymal stromal cells, which are therefore obtained non-invasively
“UC-MSCs are the most primitive type of MSC, as evidenced by their higher expression of markers Oct4, Nanog, Sox2 and KLF4 “.
Umbilical cord derived mesenchymal stem cells have the ability to differentiate into different cell types and have the highest proliferation rate among the three types of stem cells mentioned (adipose, bone marrow, umbilical cord tissue).

It is known that, like MSCs from adipose tissue and bone marrow, MSC-MSs secrete growth factors, cytokines and chemokines, improving various mechanisms of cell repair. All these functions contribute to the anti-inflammatory and immunomodulatory properties of MSCs.

Non-invasive cell product
The UC-MSC collection procedure is non-invasive as it does not require removal from the patient. MSCs are taken directly from the area of the ethically donated human umbilical cord.
UC-MSCs also have a higher proliferative potential than BMSC and ASC, which means they multiply more efficiently in vitro, providing greater efficiency in obtaining more cells.
Studies have shown that genes for UC-MSCs associated with cell proliferation (EGF), PI3K-NFkB signaling (TEK) and neurogenesis (RTN1, NPPB and NRP2) are upregulated. (increased number of receptors) in UC-MSC compared to BM-MSC.
The image below shows a comparison between BMSC, ADSC and UC-MSC.

How do mesenchymal stem cells work in the body?
Mesenchymal stem cells use their self-renewing, immunomodulatory, anti-inflammatory, signaling and differentiating properties to influence positive changes in the body. Mesenchymal stem cells (MSCs) also have the ability to self-renew by dividing and developing into a variety of specialized cell types present in a particular tissue or organ. Mesenchymal stem cells are adult stem cells, which means that they do not pose an ethical problem, MSCs are not obtained from embryonic material.
Immunomodulatory (regulating the immune system)
Mesenchymal stem cells (MSCs) can regulate the immune system, promoting an inflammatory response when the immune system is under-active and reducing inflammation when the immune system is over-active. MSCs may play a key role in preventing the immune system from attacking itself, similar to what can be seen in many autoimmune diseases. According to a 2013 study by Bernardo. When exposed to a sufficient amount of proinflammatory markers (cytokines), MSCs react by promoting an immunosuppressive response, weakening inflammation and promoting tissue homeostasis.
According to a 2019 study by Jiang
“Depending on the type or signal strength, MSCs secrete cytokines to stimulate or suppress immune responses to maintain immune balance.”
This balance is described in the same study in the figure below.

Anti-inflammatory (reducing harmful inflammation)
Inflammation is the response of the immune system to protect the body from harmful external stimuli, as well as help and recovery of the body. However, if the regulation is out of order, inflammation can be detrimental to the body. An immune system that is not regulated for an extended period can lead to a variety of autoimmune conditions, such as multiple sclerosis, type 1 diabetes, inflammatory bowel disease, or lupus.
The anti-inflammatory properties of MSCs play a key role in their therapeutic potential.

How MSCs Reduce Inflammation
“MSCs from various sources reduce inflammation by decreasing the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) and increasing secretion of prostaglandin (PGE2) and interleukin-6 (IL-6) ”.
According to a 2020 study by Gugjoo:
“In general, the central role of mesenchymal stem cells (MSCs) in maintaining homeostasis (immunomodulation and anti-inflammatory activity) occurs through interaction with immune cells and is mediated by cytokines, chemokines. , cell surface molecules and metabolic pathways.MSCs suppress T-cell proliferation, cytokine secretion and cytotoxicity ”
By secretion of MSCs and extracellular vesicles (signaling)
The regenerative effects of mesenchymal stem cells depend not only on their ability to differentiate and replace damaged tissues, but also mediated by their secretion through paracrine mechanisms.
The secret of MSCs is a set of bioactive factors that are secreted into the body, including cytokines, growth factors, extracellular vesicles, neurotrophins, soluble proteins, lipids and nucleic acids. {{1} }
Secreted secretomes play an important role in the regulation of many physiological processes, and they are of increasing interest as potential biomarkers and therapeutic targets in diseases.
According to a 2016 study by Harutyunyan et al. UC-MSC demonstrate an increased secretion of neurotrophic factors such as bFGF, nerve growth factor (NGF), neurotrophin 3 (NT3), neurotrophin 4 (NT4) and n glial neurotrophic factor (GDNF) versus bone marrow-derived (BM-MSC) and adipose tissue-derived (AT-MSC).
In addition, UC-MSCs secrete significantly higher amounts of several important cytokines and hematopoietic growth factors, including G-CSF, GM-CSF, LIF, IL-1α, IL-6, IL-8 and IL-11. compared to BM-MSC. This suggests that UC-MSCs may be more powerful than other MSC sources.
Homing properties (how MSCs know where to go)
One of the key benefits of mesenchymal stem cells is their ability to target specific areas of concern due to their intrinsic homing capabilities. Homing of mesenchymal stem cells when administered systemically can be defined as exit from the bloodstream and migration to the site of injury.
Based on a 2019 study by Ullah.
System homing is a multi-step process governed by specific molecular interactions. “The systemic homing process can be divided into five stages: (1) snapping and rolling, (2) activating, (3) stopping, (4) transmigration or diapedesis, and (5) migration.”
This process is shown in the figure below.


Differentiation (becoming new cell types)
Mesenchymal stem cells are multipotent stem cells that can self-renew and differentiate into different cell types. In other words, mesenchymal stem cells can become many different types of cells, including: adipose tissue, cartilage, muscle, tendons / ligaments, bones, neurons and hepatocytes.
According to a 2016 study by Almalk – “Differentiation of MSCs into specific mature cell types are controlled by various cytokines, growth factors, extracellular matrix molecules, and transcription factors (TF).
Mesenchymal stem cells contribute to tissue regeneration and differentiation, including maintaining homeostasis and function, adapting to altered metabolic or environmental requirements, and repairing damaged tissue.
Conclusion
There are many studies on the mechanisms of mesenchymal stem cells (MSCs). Many studies have highlighted their diverse potential, including self-renewing, immunomodulatory, anti-inflammatory, signaling, and differentiating properties. These characteristics allow MSCs to be used in a variety of clinical settings in multiple degenerative conditions.

Research indicates that umbilical cord tissue derived MSCs (UC-MSCs) may be more effective than other sources of mesenchymal stem cells, thus potentially increasing their clinical efficacy.
At our clinic, we offer treatment for a variety of conditions, including multiple sclerosis, Crohn’s disease, Parkinson’s disease, and other autoimmune conditions using cord MSCs.

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