According to recent studies from our own research group as well as others, mesenchymal stem cells can be used for various purposes from aiding in wound healing to restoring crucial organ functions (pancreatic islet cells for diabetes patients). A possibility to treat orthopaedic disorders by stem cell therapy has received a lot of attention in the past few years.
Among the most common conditions that have been successfully treated by stem cells are osteoarthritis or rheumatoid arthritis affected joints, ligament tears, cartilage wear, tendonitis, bursitis and so on. In addition, very promising results were obtained by using MSCs for the treatment of acute myocardial infarction, one of the leading causes of death worldwide (reviewed in Carbone et al., 2021). A recent study by Lanzoni et al. (2021) showed the use of cord blood derived MSCs for the treatment of acute respiratory distress syndrome that is associated with high mortality in COVID-19 patients. Stem cells are also are being tested for the use to grow skin grafts and for cornea repair for patients with severe burns or chemical burns. Using stem cells for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is also a very active field of research.
There are different ways in which stem cells can improve symptoms of various diseases and this is not limited to the restoration of a particular tissue type. MSCs were shown to have local immunomodulatory properties, i.e., they adjust the immune response to the appropriate level. It is thought that they are able to do so by the directly interacting with immune cells at the affected site, and by secreting various factors that modulate the immune response, both locally and throughout the body. It is widely accepted that both acute and chronic inflammation resulting from either exposure to an irritant or from inadequately reacting to the body’s own molecules can be very damaging. Persistent inflammation not only contributes to autoimmune conditions but can be a factor in the development of cancer and is also linked to ageing. This is why the immunomodulatory properties of stem cells are of particular interest in the cell therapy of various diseases, in which inflammation plays a significant role, one of these being osteoarthritis. It was shown that MSCs can affect both innate and adaptive immune responses by interacting with B cells, T cells, natural killer cells, dendritic cells, macrophages, monocytes and neutrophils; they also secrete certain trophic factors, i.e., cytokines, chemokines, growth factors (reviewed in Song et al., 2020).
One of the most important properties of MSCs for the treatment of orthopaedic conditions is the secretion of the extracellular matrix components. Extracellular matrix (ECM) is a three-dimensional network of various fibrillar proteins such as collagen, elastin, glycoproteins, etc., enzymes that remodel it and cells that produce macromolecules to build it; the main function of the ECM is to support and keep together certain cells, thus forming tissues and organs. Articular, or elastic, cartilage is a dense ECM that is mainly composed of various collagens, proteoglycans, non-collagenous proteins and water. This ECM is produced by chondrocytes that reside within the ECM itself. Osteoarthritis, the most common disease of joints, is a progressive degeneration process of cartilage. Cartilage generally has a limited regeneration capacity due to a lack of vascularization and nerves within the tissue. Thus, once the joint is damaged by injury or in cases the cartilage is weak due to some genetic factors, the tissue is unable regenerate without some external intervention, causing an affected patient constant pain and limiting the mobility. For this reason, the use of mesenchymal stem cells has a great potential not only for alleviating the symptoms of joint degenerative conditions by reducing inflammation but also to restore the destructed cartilage, thus allowing for the damage reversal.
Current challenges with using MSCs in cell therapy are mainly associated with the fact that the cells coming from various sources usually exhibit some variation in their differentiation and immunomodulation potential. Hence, often it is very important to have robust and reliable protocols to reprogramme MSCs in vitro before transplantation in order to improve their survival and differentiation into a desired cell lineage. For example, in case of cartilage regeneration with stem cells close attention should be paid to what type of cartilage is produced by transplanted stem cells. Often, transplanted MSCs start producing fibrocartilage instead of hyaline cartilage, which does not restore the mobility of the joint.
At StemCellX we strive to achieve the optimal quality MSCs by rigorously screening and testing cells we isolate. We developed unique, high scale methods to culture and propagate MSCs that once injected will produce the correct type of proteins and molecules in order to restore the elastic cartilage in the joint.
Carbone, R.G., Monselise, A., Bottino, G., Negrini, S. and Puppo, F. Stem cells therapy in acute myocardial infarction: a new era? Clin Exp Med. https://doi.org/10.1007/s10238-021-00682-3 (2021).
Lanzoni, G. et al. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: a double-blind, phase 1/2a, randomized controlled trial. Stem Cells Transl. Med. https://doi.org/10.1002/sctm.20-0472 (2021).
Song, N., Scholtemeijer, M., Shah, K. Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends in Pharmacological Sciences. https://doi.org/10.1016/j.tips.2020.06.009 (2020).
