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 honing to sites of damage, paracrine signalling, regulating the immune response, and affecting the microenvironment.
In combination, these traits make Mesenchymal stem cells of intense therapeutic interest, because they represent a population of cells with the potential to treat a wide range of acute and degenerative diseases.
- Well-Characterized: Mesenchymal stem cells are a well-characterized population of adult stem cells, with over 36,000 scientific articles published about them.
- Non-Controversial: Mesenchymal stem cells avoid the ethical issues of embryonic stem cells, as they can be derived from sources that include adult bone marrow and adipose tissue.
- Diverse Differentiation Potential: Mesenchymal stem cells can form a variety of cell types in the laboratory, including those of both intra- and extra-mesenchymal lineage. These cell types include: fat (adipocytes), bone (osteoblasts), skin (dermal cells), nerve (neural cells), cartilage (chondrocytes), muscle (skeletal myocytes), tendons (tenocytes), marrow stroma, ligaments, and more.
- Ease of Growth in Culture: Advanced knowledge exists for how to growMesenchymal stem cells in culture, including protocols for isolation, expansion, and differentiation.
- Flexible Propagation: Mesenchymal stem cells can be grown and propagated in culture for extended periods, without losing differentiation potential.
- Role as Regulatory Cells: Mesenchymal stem cells synthesize and secrete a variety of macromolecules that are known regulators of hematopoietic and bone-resorbing cells.
- Favorable Immune Status:Mesenchymal stem cells lack the co-stimulatory molecules of the B7 family that are required to initiate an immune response. This allows the administration of MSC preparations across MHC barriers without concern for immunological rejection or the need for immunosuppression, making Mesenchymal stem cells a universal stem cells source.
Mesenchymal Stem Cell Therapy from the Umbilical Cord
Mesencymal stem cells are early passage multipotent progenitor cells derived from human cord tissue that are capable of supporting hematopoiesis and differentiating into multiple lineages (osteogenic, adipogenic, chondrogenic, neurogenic, myogenic, and cardiomyogenic.)
For acceptance: Maternal blood and cord blood is tested negative for HIV I&II, HCV, CMV IgG/IgM, syphilis IgG/IgM antibodies and Hepatitis B surface antigen. Free of bacterial and fungal contamination.
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.
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 the immune response, and affecting the microenvironment.
Young Stem Cells and Old Stem Cells:
Umbilical cord tissue represents a unique, easy accessible and noncontroversial source of early stem cells that can be readily processed for therapeutic use.
Our laboratories have compared the properties of Umbilical cord mesenchymal stem cells and from adult sources such as adipose and found some important differences:
- Umbilical cord mesenchymal stem cells appear to lack some immune properties compared with adult stem cells
- Umbilical cord mesenchymal stem cells lack class II HLA, whereas adult mesenchymal stem cells express these antigens. This is very important in regards to facilitating "acceptance" of transplanted cells.
- Umbilical cord mesenchymal stem cells express a very different range and level of growth factors & specific cytokines when compared to adult mesenchymal stem cells.
The difference between young and old mesenchymal stem cells:
The difference between young and old MSCs in morphology, cell surface antigen phenotype, proliferation, gene expression and immunomodulatory ability are proven. When you expand the numbers of young mesenchymal stem cells into further passage, senescent MSCs display a characteristically enlarged and flattened morphology and different gene expression profiles.
Human mesenchymal stem cells have insufficient telomerase activity to overcome progressive telomere shortening caused by end-replication problems and oxidative stress associated with higher rates of culture.
Optimising Mesenchymal Stem Cell Culture for Therapeutic Use:
Over a two to three weeks period Mesenchymal stem cells can rapidly proliferate achieving potentially thousands of fold expanded cells. However, inappropriate expansion reduces the quality of the MSCs. In addition, particular therapeutic properties of the mesenchymal stem cells will be lost during prolonged culture, for example, the cardio protective effect of mesenchymal stem cells grown to passage 3 is significantly reduced compared to passage 1 mesenchymal stem cells.
In our laboratories as a standard, the most important parameter we use for determining clinical cell culture is using population doubling time. Population doubling time refers to the number of times two-fold increase (doubling) of the cells in culture. Population doubling time directly correlates with replicative senescence, loss of potency and genomic instability. Mesenchymal stem cell senescence is reported in cultures with population doubling time from 10-40. This worsens and shortens each passage of culture the cells are put through.
Most other stem cell labs continue to culture cells into passage 3. This means that the original culture flask has filled its surface of around 80% and a portion of the cells are then seeded into a new culture flask to grow further. Each time a portion of cells are transferred into new flasks to grow is classed as a passage. Each passage can have between 10-40 doublings depending on starting volume of cells. So in theory cells which have been cultured to passage 3 could have undergone 30-120 doublings.
Thus, our laboratories maintain just passage 1 culture with a restriction on doubling of 5-10 times. This maintains their naive status and higher activity levels.
Thus, as naïve cells, mesenchymal stem cells extracted from cord tissues have greater therapeutic potential than adult cells. Studies have also shown that cord tissue–derived mesenchymal stem cells appear to have greater in vitro capacity for expansion and shorter doubling times; they can therefore generate a larger cell mass in less time than can be achieved with adult stem cells. This property may be related to greater length of chromosomal telomeres, which have been found to shorten with increased rounds of cell division. This suggests that primitive mesenchymal stem cells have a greater ability to expand in culture than do adult mesenchymal stem cells, perhaps due to their relative youth.