Mesenchymal stem cells (MSCs) are one of the most researched types of cells for regenerative stem cell-based therapies. This is due to their diversified capabilities that can lead to promising outcomes in a variety of different conditions. This article outlines the three most common sources of mesenchymal stem cells (MSCs) as well as their primary mechanisms of action (how they work).
What are mesenchymal stem cells?
Stem cells are the body’s raw materials — cells from which all other cells with specialized functions are created. Mesenchymal stem cells are adult stem cells that have self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties. Mesenchymal stem cells (MSCs), self renewal capacity is characterized by their ability to divide and develop into multiple specialized cell types present in a specific tissue or organ.
Mesenchymal stem cells (MSCs) can be sourced from a variety of tissue 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-renewable, differentiation, anti-inflammatory, and immunomodulatory properties. In-vitro (performed in a laboratory setting) and in-vivo (taking place in a living organism) studies have supported the understanding mechanisms, safety, and efficacy of MSC therapy in clinical applications. (3)
According to a 2018 study conducted by Crigna, et al.
“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)
This article will focus on mesenchymal stem cells that are derived from adipose tissue (ADSCs), bone marrow (BMSCs) & umbilical cord tissue (UC-MSCs).
Adipose Tissue-Derived MSCs (ADSCs)
Adipose tissue-derived MSCs are obtained from the subcutaneous adipose tissue (fat tissue), they can be rapidly acquired in large numbers and with high cellular activity through a liposuction procedure (2).
ADSCs are likely to be more viable when sourced from a younger donor. This may prove to be an issue with older patients that participate in an autologous procedure (using your cells), as the older cells may be less fitted for long-term survival in the recipient. Adipose tissue-derived MSCs (ADSCs) from younger donors present a higher proliferation rate (survivability after transplant) when compared to elderly ones, but the differentiation capacity is maintained with aging, thus having advantages on bone marrow mesenchymal stem cells (BM-MSCs).
However, ADSCs do maintain their potential to differentiate into cells of mesodermal (middle cell layer) origin and they are commonly known for their low immunogenicity and modulatory effects. Less than 1% of them expressed the HLA-DR protein on their surface, leading to immunosuppressive effects and making them suitable for clinical applications in allogeneic transplantation and therapies for the treatment of resistant immune disorders. (2)
It is widely accepted that ADSCs can be used for a variety of different conditions. ADSCs can also be a viable source for most orthopedic treatments. Common applications may be spinal cord injury, arthritis, localized joint inflammation, knee pain, and other musculoskeletal issues.
However, there are still some challenges that surround the use of ADSCs in a clinical setting. These challenges include proliferative limitations concerning the age of cells, limited differentiation capabilities, and protocol standardization.
According to a study published by Mazini et al.
“ADSCs represent many therapeutic challenges in terms of origin, type, and the manner to use them, different recent investigations pave the way to their successful therapeutic use in tissue repair. More insights into standardizing technical use are warranted to evaluate the in-depth efficacy and safety of ADSCs-based therapy and evaluate the benefit-to-risk ratio in clinical applications. The beneficial effects of stem cells, and there with the paradigm of tissue regeneration, may not be restricted to cellular restoration, but may also be related to the transient paracrine actions of the cells.”
Bone Marrow-Derived MSCs (BM-MSCs)
Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are classified as multipotent adult stem cells, are widely used in the treatment of various diseases via their self-renewable, differentiation, and immunomodulatory properties.
“In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of BM-MSCs therapy in clinical applications. The number of clinical trials in phase I/II is accelerating; however, they are limited in the size of subjects, regulations, and standards for the preparation and transportation, and administration of BMSCs, leading to inconsistency in the input and outcome of the therapy.” (3)
Limitations
Bone Marrow harvesting is a highly invasive and painful procedure that requires general anesthesia and multiple days for hospital care. BM-MSCs constitute a rare population, with only 0.002% of the total stromal (stem) cell population, and their isolation depends on the patient status and the volume of matter collected. (2)
Similar to ADSCs bone marrow stem cell’s quantity and quality decline with age. BM-MSCs are likely to be more viable when sourced from a younger donor when employing an allogeneic (cells come from a third party) treatment. This may prove to be an issue with older patients that participate in an autologous procedure, as the older cells may be less fitted for long-term survival in the recipient. This issue is outlined by Chu et al. in a 2020 study.
