Mesenchymal Stem Cells (MSCs)
Features of MSCs
Mesenchymal stem cells (MSCs) are advantageous over other stem cells types for a variety of reasons. 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 allogeneic transplantation. MSCs reduce both the risks of rejection and complications of transplantation.
Third, there have been advances in the use of umbilical cord mesenchymal stem cells to regenerate human tissues, including cartilage, meniscus, tendons, and bone fractures, because MSCs can exert regenerative effects through homing to sites of damage, paracrine signalling, regulating immune responses, and positively affecting the microenvironment.
Mesenchymal stem cells are multipotent adult stem cells that are present in multiple tissues, including umbilical cord, bone marrow and fat tissue. Mesenchymal stem cells can self-renew by dividing and can differentiate into multiple tissues including bone, cartilage, muscle, and connective tissue. In Juvenile states MSCs can also differentiate into other cell types such as cardiomyocytes, neural precursors and/or mature neurons, however this ability reduces with ageing or multiple passage culture expansion of MSCs.
MSCs have shown the ability to avoid a negative response from a person’s immune system, allowing the cells to be transplanted in a wide range of people without fear of rejection. These transplants vastly increase the body’s natural healing abilities and have potent anti-inflammatory and immunosuppressive responses.
MSCs possess several properties that are advantageous in the field of regenerative medicine and tissue engineering. Their potential for immunomodulatory, immunosuppressive, and regenerative properties has been widely used in the form of cell-based therapy for inflammatory, immune-related, and degenerative diseases.
MSCs have the ability for selective migration toward a site of injury, in a process called homing. This means they can act as an efficient surveillance system, which detects changes in the environment such as the presence of inflammation. They have in fact been shown to travel to the site of inflammation from the injection site and subsequently induce the release of bioactive molecules.
Their use is beneficial in tissue regeneration given their capability to differentiate into several cell lineages, their homing capacity, angiogenesis, anti-apoptotic activity, and secretion of bioactive soluble factors (growth factors, cytokines, extracellular vesicles / EVs)
MSCs function in immunomodulation by inhibiting the proliferation of several types of immune cells through the action of cytokines and regulatory factors. Their anti-inflammatory effect decreases an immune response to inflammation, thus protecting the host. Anti-apoptotic activity of MSCs protects injured cells and preserves organ function.
Over 1,000,000 patients around the world have now been part of clinical studies or received stem cell treatment, with only minimal adverse reactions such as low grade fever for 24 hours, or trauma at the injection site. Safety profiling of MSC use in humans has been well achieved.
Mesenchymal Stem Cell Characteristics
Stem Cell Markers:
Cell surface markers are expressed on the cell surface and can be used to define cell subtypes as well as function when they are labeled with fluorescent-labeled antibodies and analyzed by flow cytometry.
MSCs are adult stem cells which identified by adherence to plastic, expression of cell surface positive markers including CD73, CD90, CD105, and negative for hematopoietic markers.
Stem Cell Differentiation:
MSCs also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), and adipocytes (fat cells), neuronal cells, cardiomyocytes, and more.
As an international standard MSC characterization studies require 3 standard differentiation’s when analyzing MSC batch production at SC21 laboratory.
Umbilical Cord Mesenchymal Stem Cells (UC-MSCs)
Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional stem cells isolated and cultured from umbilical cord. UC-MSCs possess the characteristics of highly self-renewal, increased multi-directional differentiation potential, low immunogenicity, and the production of highly therapeutic bioactive soluble factors.
There are a number of advantages associated with using mesenchymal stem cells derived from the umbilical cord. Firstly, mesenchymal stem cells have no ethical concerns over the harvest of these cells. Also, cell harvesting is non-invasive, so there are no pain or medical risks involved to the patient. Because these cells are relatively young (±9 months), they also give rise to mesenchymal stem cells that are juvenile and possess the highest level of therapeutic potential; especially when you compare these cells to mesenchymal stem cells that are harvested from bone marrow or adipose tissue (aged cells).
UC-MSCs have shown the ability of faster self-renewal and to differentiate into three germ layers, to accumulate in damaged tissue or inflamed regions, to promote tissue repair, and to modulate immune response.
Keeping MSCs Young in Function
During culture, MSCs are expanded in numbers to reach therapeutically beneficial numbers. However, every time a stem cell divides (self-renews) it loses some of its abilities as a stem cell – stemness. In a way each time a cell divides it ages, becoming slower and less able to perform its specialist tasks. At StemCells21 we produce high grade UCMSCs – Passage 1 Mesenchymal Stem Cells (P1 MSCs).
The Importance of Early Passage MSCs
Human MSCs subjected to extensive in-vitro passage can undergo morphological, phenotypic, and genetic changes.
Extensive pre-clinical culture expansion inevitably drives cells toward replicative “aging” and a consequent decline in quality. The late passage MSCs resemble biologically aged cells, which have been reported to show senescence signatures, diminished immunosuppressive capacity, and weakened regenerative potential as well as pro-inflammatory features.
MSCs which have been cultured, even to passage 3, present a decay in telomerase activity and a change in chromosomal morphology with potential anomalous karyotypes, indicating senescence leading to impaired stemness and desired function of the stem cells.
As an example, passage 1 umbilical cord mesenchymal stem cells hold neural differentiation potential, and produce neurotrophic growth factors, with this ability being completely lost in later passage cultured cells.
At SC21 we produce only early passage MSCs which have been subject to limited expansion, in turn maintaining all the desirable qualities of young stem cells.