Mesenchymal stem cells are a class of multipotent cells found in human tissues, such as bone marrow, adipose tissue, dental pulp, and periosteum, a layer of connective tissue that envelops the bones. They are also known as: Medicinal Signaling Cells, Mesenchymal Stromal Cells, and Marrow Stromal Cells. Given this naming variability, as well as urging by Dr. Caplan to rename the cells so that patients don’t assume specific medical benefits, these cells are best known as: MSCs.
It should be noted that in many articles on this site, we still use the term mesenchymal stem cells, simply because the short acronym “MSC” on Google does not bring up articles about this cell type.
Rather, it returns results about industrial supplies and cruises. Sadly, Google is not yet able to support our renaming of this cell type simply because its search feed is a reflection of supply and demand, and there are too many terms and meanings associated with a three-letter acronym like MSC.
MSCs, are of intense therapeutic interest because they represent a population of cells that have the potential to treat a wide range of acute and degenerative diseases. First, they avoid the ethical issues that surround embryonic stem cell research. Second, repeated studies have found MSCs to be immuno-privileged, which make them an advantageous cell type for allogenic transplantation. MSCs reduce both the risks of rejection and complications of transplantation.
There have also been notable advances in the use of autologous mesenchymal stem cells to regenerate human tissues, including cartilage, meniscus, tendons, bone fractures, and more.
For a decade or so, MSCs were largely perceived to be a supportive, feeder layer for hematopoietic stem cells (HSCs). Then sentiment within the research community swung strongly in the opposite direction, with MSCs hastily labeled as “stem cells,” despite demonstrating a considerably limited differentiation potential. This characterization was misleading and drove research towards outcomes that involved semi-differentiated and often non-engrafting cells.
Indeed, the traditional view that mesenchymal stem cells heal by maturing into replacement cells for damaged tissue is either partially (or fully) untrue. Current research suggests that the power of MSCs stems from their ability to regulate the immune response and influence the human body’s own regenerative machinery. This understanding is critical to pursing effective avenues for the commercialization of MSC products, technologies, and therapies. How MSCs exert their effects continues to be explored across the public, private, academic, and government sectors.
In recent years, human mesenchymal stem cells (hMSCs) have become a foundational technology for a number of cell-based products. MSCs are multipotent progenitor cells with multilineage potential with a capacity to differentiate into adipocytes, osteocytes, and chondrocytes.
Moreover, they are capable of migrating to sites of inflammation and exerting potent immunosuppressive and antiinflammatory effects by interacting with lymphocytes associated with both innate and adaptive immune systems. They can be easily isolated from a varierty of tissue sources and expanded for widespread therapeutic commercialization.
MSC Clinical Trials
A search of ClinicalTrials.gov reveals that MSCs are being tested in at least 964 clinical trials for cell therapy, gene therapy, tissue-engineered and combination products. MSCs are being studied in clinical trials for indications that include: orthopedic injuries, graft-versus-host disease (GvHD) following bone marrow transplantation, cardiovascular diseases, autoimmune diseases, and liver diseases.
In addition, gene editing of MSCs for overexpressing antitumor genes or therapeutic factors has broadened their application.
MSC product approvals are relatively early-stage, but are gradually accelerating. For example, regulatory agencies in Canada and New Zealand have approved Prochymal (Osiris Therapeutics), which contains allogeneic bone-marrow-derived MSCs to treat steroid-resistant GvHD in children. South Korea has approved two MSC products: one is an allogeneic umbilical cord blood-derived MSC-based product (Cartistem) to treat degenerative arthritis and another is an autologous adipose tissue-derived MSC product (Cupistem) to treat anal fistulas in patients with Crohn’s disease. Alofisel (TiGenix and Takeda, approved in Europe), Temcell (JCR pharmaceuticals, approved in Japan), Heartsheet (Terumo, approved in Japan), and Cellgram-AMI (FCB-Pharmicell, approved in South Korea) are other products made containing MSCs.
In another intriguing example, Cynata Therapeutics is developing induced pluripotent stem cell derived MSCs, using its Cymerus technology. The Cymerus™ technology utilizes induced pluripotent stem cells (iPSCs) originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for differentiating the cells into mesenchymal stem cells (MSCs).
There are numerous other MSC product candidates as well.
MSC-Derived Extracellular Vesicles and Exosomes
Even if the MSCs do not engraft or persist long term, MSCs excrete extracellular vesicles (EVs) and exosomes that appear to produce paracrine effects after leaving the target site. Thus, there is accelerating interest in exploring MSC-derived exosomes/EVs for their potential as a cell-free alternative to MSC-based therapies.
In recent years, some researchers have shifted their focus from MSCs to components obtained from MSCs. These components include extracts, microvesicles and exosomes from MSCs that can perform specific biological activities. Similar to the whole cells of MSCs, exosomes from MSCs have demonstrated a capacity to repair tissue damage, suppress the inflammatory response and modulate the human immune system.
Exosomes isolated from adipose tissue have been found to accelerate cutaneous wound healing through impacting the characteristics of fibroblasts. Extracellular vesicles from MSCs have also shown similar properties. A single intravenous injection of exosomes has been observed to improve cardiac function after myocardial infarction. Studies have also indicated that exosomes from MSCs can promote cardiac stem cell proliferation in vitro. Further studies have revealed that exosomes from MSCs can be used effectively to treat acute kidney injury, fibrotic liver and musculoskeletal disorders.
Despite these promising applications, there are also risks associated with MSC-derived exosomes. It has been documented that MSC-derived exosomes are involved in tumor growth, angiogenesis, metastasis, and invasion. Furthermore, there is preliminary evidence that indicates that the role of MSC exosomes as nanocarriers may cause effects related to multi-drug resistance mechanisms or immune regulation. Potentially, the role of MSC-exosomes in cancer progression could be leveraged to create effective treatment protocols, but this area of study requires further research.
Diverse MSC Applications
Apart from the therapeutic applications described above, MSCs also find applications in within the cosmeceutical and food industries. L’Oreal and Johnson & Johnson are now focused on adding biological components, such as cytokines and growth factors from MSCs, to their personal care products and testing these products on bioprinted human skin models.
The “clean meat” industry is focusing on solving the upcoming global demand for meat innovatively by using MSCs as a raw material to produce engineered in vitro produced meat. Extensive research is being directed at using muscle precursor cells (satellite cells) and fat cells obtained from MSCs for this purpose.
The MSC industry is also witnessing a huge demand for cGMP bioprocess media and ancillary materials (AMs), such as reagents.
Global Market for MSCs
Increasingly in recent years, MSC are regarded as a novel treatment approach and a therapeutic candidate for use within regenerative medicine. Most often, the therapeutic potential of MSCs is exploited via their paracrine effect on the surrounding environment. Specifically, MSCs have demonstrated the capacity to induce revascularization, protecting tissues from stress-induced apoptosis, and positively affecting the inflammatory response.
MSC-derived exosomes also appear to be an intriguing, cell-free approach to mediating many of the therapeutic effects traditionally associated with MSC-based therapies.
To date, outcomes from MSC-based therapies have been encouraging across various clinical fields, based on in vitro and in vivo research studies and at least 964 clinical trials registered on ClinicaTrials.gov. Because that database contains approximately 75-80% of trials worldwide, the total number is likely much higher.
Interested to learn more about the rapidly expanding market for MSCs?