Mesenchymal Stem Cell Therapy

Mesenchymal stem cells (MSCs) are ideal for cell therapy in many inflammatory diseases due to their tissue repair potential and immunosuppressive properties. Compared with other cell types, their low immunogenicity and immunosuppressive properties exacerbate the low or weak immune response resulting from allergenic MSC transplantation. Further research is needed to enhance the efficacy of MSCs as cell therapy for tissue repair and inflammatory diseases.

Mesenchymal stem cells (MSCs) are classified into different groups according to the cell source. They are:

• Adipose tissue-derived pluripotent stem cells (ASCs)
• Bone marrow-derived pluripotent stem cells (BM-MSCs) and
• Umbilical cord tissue-derived mesenchymal stem cells (UC-MSCs)
• Adipose tissue-derived pluripotent stem cells (ASCs)

Adipose tissue-derived mesenchymal stem cells are extracted from subcutaneous or adipose tissue. Liposuction can rapidly collect these cells in massive quantities, with high cellular activity.

Adipose-derived stem cells from younger donors are likely to be more viable. When older people undergo autologous surgery (using their own cells), this can become a problem, as older cells may not be as suitable for the recipient’s long-term survival. Adipose-derived stem cells (ADSCs) from younger donors have a higher proliferation rate (ability to survive after transplantation) than older donors, but they retain their differentiation capacity, giving them an advantage over bone marrow mesenchymal stem cells (BM-MSCs).

Despite their poor immunogenicity and modulatory effects, it is known that MSCs derived from MSCs retain their ability to develop into mesoderm cells (the middle cell layer). Because less than 1% of these cells had surface expression of the HLA-DR protein, which has immunosuppressive effects, these cells are suitable for clinical use in allogeneic organ transplantation and the treatment of refractory immune diseases.

It is well known that stem cells derived from stem cells can be used in a wide range of conditions. Furthermore, stem cells derived from stem cells are a good option for most orthopedic procedures. These cells are frequently used for conditions such as arthritis, knee pain, spinal cord injuries, osteoarthritis, and other musculoskeletal problems.

However, there are still many challenges in using stem cell-derived stem cells in a therapeutic setting. These include limited differentiation capabilities, standardization of protocols, and proliferative limitations associated with cell age.

Bone marrow-derived pluripotent stem cells (BM-MSCs)

Because of their ability to self-renew, differentiate, and modulate immunity, bone marrow-derived mesenchymal stem cells (BM-MSCs), which are classified as pluripotent adult stem cells, are frequently used in the treatment of a variety of disorders.

In vitro and in vivo studies have provided evidence on the mechanisms, safety, and efficacy of bone marrow-derived stem cell (BM-MSC) therapy in clinical settings. The number of phase I and II clinical trials is increasing, but they are limited by participant size restrictions, regulations, and guidelines regarding the handling, administration, and transfer of BMSCs. As a result, treatment outcomes and outcomes vary.

Restrictions :

Bone marrow extraction is a highly invasive and uncomfortable surgical procedure, requiring a hospital stay of several days under general anesthesia. BM-MSCs constitute only 0.002% of stem cells, making them a rare group, and their isolation depends on the patient’s condition and the amount of material harvested.

The quantity and quality of bone marrow stem cells decline with age, just as does the quality of ADSCs. When using allogeneic treatment (cells from a third donor), stem cells derived from stem cells from younger donors are more viable. However, when older people undergo autologous transplantation, this can become a problem, as the older recipient’s cells may not be suitable for long-term survival.

Most preclinical and clinical studies have demonstrated the ability of bone marrow stem cells (BMSCs) to treat a range of diseases with minimal side effects during follow-up periods. Bone marrow stem cell (BM-MSC) therapy is currently used to treat sports injuries, neurological diseases, and osteoporosis.

Umbilical cord tissue-derived mesenchymal stem cells (UC-MSCs)

The perivascular area of ​​the umbilical cord, Wharton’s jelly, and the cord lining are sources of non-cancerous mesenchymal stem cells. Because the umbilical cord is often a neglected tissue, it is a rich source of mesenchymal stem cells that can be collected non-invasively.

Of the three types of stem cells described (adipose cells, bone marrow, and umbilical cord tissue), mesenchymal stem cells produced from umbilical cord tissue have the highest proliferation rate and ability to develop into different cell types.

Like mesenchymal stem cells derived from bone marrow and adipose tissue, MSCs derived from bone marrow and adipose tissue are known to release chemokines, cytokines, and growth factors that promote various cell-healing pathways. All of these roles support MSCs’ immunomodulatory and anti-inflammatory capabilities.

Non-surgical cellular product

Extracting mesenchymal stem cells from the umbilical cord is a non-surgical procedure, as the patient does not need to have them removed. The mesenchymal stem cells are extracted directly from a segment of the human umbilical cord, ethically donated.

Because UC pluripotent stem cells proliferate more efficiently in the laboratory than stem cells from BMSCs and ASCs, it is possible to obtain higher cell numbers more efficiently.

The table below shows a comparison between adipose tissue-derived mesenchymal stem cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and umbilical cord tissue-derived mesenchymal stem cells (UC-MSCs).

• How do mesenchymal stem cells work in the body?

Mesenchymal stem cells utilize their differentiation, self-renewal, immunomodulatory, anti-inflammatory, and signaling capabilities to effect positive changes in the body. In addition to their self-renewal capabilities, mesenchymal stem cells (MSCs) can divide and differentiate into various specialized cell types found in a given tissue or organ. Because MSCs are adult stem cells and not derived from embryonic material, they do not raise any ethical issues.

• Immunomodulation (regulation of the immune system)

By stimulating the inflammatory response when the immune system is weakened and reducing inflammation when it is overactive, mesenchymal stem cells (MSCs) can control the immune system. These cells have a remarkable ability to prevent autoimmune diseases when the immune system attacks the body. Research conducted by Bernardo et al. in 2013 indicates that these cells stimulate an immunosuppressive response to reduce inflammation and support tissue homeostasis in response to exposure to high concentrations of pro-inflammatory signals (cytokines).

• Anti-inflammatory (reduce harmful inflammation)

The immune system’s response to any adverse external stimulus is inflammation, which also helps support and repair the body. On the other hand, when inflammation is dysregulated, the body can suffer. Long-term immune dysregulation can lead to a number of autoimmune diseases, including lupus, multiple sclerosis, type 1 diabetes, and inflammatory bowel disease.

Mesenchymal stem cell secretions and extracellular vesicles (exosome signaling)

Mesenchymal stem cells can replace and differentiate damaged tissue, but their reparative actions are also mediated by their secretions through paracrine processes.

The body absorbs a range of biologically active substances known as mesenchymal stem cell secretions, which include cytokines, growth factors, neurotrophins, soluble proteins, lipids, and nucleic acids.

Secretions produced are gaining increasing importance as potential biomarkers and therapeutic targets for diseases and play important roles in controlling many physiological processes.

Compared with bone marrow-derived (BM-MSCs) and adipose tissue-derived (AT-MSCs), UC-MSCs exhibit increased secretion of neurotrophic factors, including bFGF, nerve growth factor (NGF), neurotrophin 3 (NT3), neurotrophin 4 (NT4), and glial cell-derived neurotrophic factor (GDNF).

Furthermore, compared to bone marrow-derived pluripotent stem cells (BM-MSCs), UC MSCs release significantly 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. This suggests that UC MSCs may be more effective than MSCs from other sources.

• Routing Properties: How Do MSCs Know Where to Go?

Due to their inherent homing properties, mesenchymal stem cells have the ability to specifically target affected areas, which is one of their most important advantages. When mesenchymal stem cells are administered systemically, their “homing” is the process by which they exit the circulation and travel to the site of injury.

• Differentiation: the formation of new cell types

Pluripotent stem cells, also known as mesenchymal stem cells, are capable of self-renewal and specialization into many cell types. In other words, mesenchymal stem cells can differentiate into a wide range of cell types, such as liver cells, cartilage cells, muscle cells, tendons/ligaments cells, bone cells, and adipose tissue cells.

Mesenchymal stem cells support tissue homeostasis and function, the ability to adapt to changing metabolic or environmental demands, and tissue repair by assisting in tissue regeneration and differentiation.