Image Credits: The Stem Cellar
Article Authors: Gordon Slater|Tandose Sambo
“Health is a large word. It embraces not the body only, but the mind and spirit as well; …and not today’s pain or pleasure alone, but the whole being and outlook of a man.”
– James H. West
The future of medicine is in stem cells and regenerative therapies. With the utilization of stem cells becoming more prevalent in the medical realms since their discovery and introduction to medical research, the advances in medical research are taking note of the benefits of the therapy.
One of the areas of medical advancement that has benefited from stem cell therapies is the process of tissue engineering and regeneration. The ability to successfully engineer various tissues is one that is becoming increasingly more beneficial to medical treatment. The therapy is still in its relative infancy, and limitations of stem cell science are being overcome by the utilization of a combination of stem cells with co-culture systems. Stem cells do have regenerative abilities, and the potential to regenerate into differentiated cells according to the environment that they are placed in. They are the starting point for life, and cell differentiation that leads to organism development.
When stem cells are applied in co-cultures, they promote tissue growth and repair via a multi-fold approach. One of the influences is that of an enhancer in the culture that they are introduced to, via enhancing the existent terminally differentiated cells. In an instance where the cells are few in number, the stem cells will actually facilitate the proliferation of more of those types of cells, and increase cell survival, proliferation, phenotype maintenance and organization.
Stem cells have a multitude of properties, and have the ability to regulate cell functions within living systems. They assist with the regulation of the co-culture that they are integrated with, via providing a regulatory control loop that enables the system to actually sustain itself, and heal, restore and repair where the system needs to. Via the synergistic operation of the stem cells with their co-culture cells, the stem cells have the ability to act in supporting roles to the system. As their functions are diverse, where they are placed, the stem cells will quickly adapt.
The design of a co-culture is one that aims to optimize cellular interactions, and improve a biological system. The system could be one that is of a human system, or in some instances in an animal system. The anticipated interactions will be via direct cell–cell contact, cell–ECM adhesion and transfer of signalling molecules. These interactions, while detected by science, are actually still in the process of being deeply understood, in terms of their mechanisms of action.
The interaction of stem cells and existent terminally differentiated cells in a co-culture is one that is being investigated. What is known is that they do communicate via a mechanism that is still being elucidated. The primary elements of the communication paths include interaction via growth factor dose and dosing regimens. Additional factors within the extracellular matrix (ECM) have also been found to influence the extent of communication between the stem cells and their co-culture counterparts. The ECM influence on the organism is one that is much like larger organisms and their environment. The more nourishing and nurturing the environment, the more likely that the stem cells will maintain and regulate the biological functions of the systems that they are regulating.
As the tissue engineering and engineering realms understand the relevant factors that lead to improvements in co-culture regulation, the more success there will be in vivo transfers of the system. Tissue engineering is a novel activity that will generate many benefits once it is mastered. The interaction of stem cells and terminally differentiated cells is an engineered environment that doesn’t take place within the body. As an experiment that is geared towards looking at all possibilities, the notion that knowing what happens in an extreme condition, will ready the scientists to understand what will happen in the body is currently being applied. The test conditions will generate the conditions that will ensure that the real conditions will be more readily understood once they are attempted.
Orthopaedic Soft Tissues
With co-culture conditions generating favorable results, the next steps would involve the process of actually utilizing them in the regeneration of various cells across the body. Within the body, cartilage is one of those systems that takes a very long time to heal itself once it has lost some of its cells due to damage via sporting activity, or via degenerative processes such as osteoarthritis.
Cartilage as a cellular system is one that is monocellular in nature, and it is generally one that has few vessels and nerves. The nature of cartilage is one that makes it so difficult to regenerate. Systems that are highly vascularized tend to be better able to regenerate themselves because of the access of blood flow and nutrients to the area. The nature of cartilage, therefore makes it one of the more challenging locations to utilize as a cell source for tissue engineering.
Regenerating the area, therefore becomes one of the biomedical grand challenges. The utilization of stem cells to regenerate cartilage in vivo has proven to be successful. Via stem cell injections into an in vivo site, the ability to increase joint integrity was actually witnessed. After an incubation period, the injected stem cells enabled the body to regenerate itself, and the final results of higher expression of chondrogenic genes, and the improved mechanical integrity of the joints were noticed with time. The results proved the ability of stem cells to produce collagen types I and II, and to optimize the functions of the joint from a mechanical standpoint. Engineered cartilage is gaining traction in medical therapies. Patients who experience conditions such as osteoarthritis, will be the prime candidates for this therapy.
A Promising Future
Another future possibility is the fact that co-culture applications are now finding application in multiple spheres. With the ability to utilize more than two cell populations in a single system co-culture, the prospects of increased medical understanding of these systems are becoming better understood. Advantages of this multi-cell co-culture include the ability to heal systems such as cardiac and vascular tissue. In research conditions, conditions such as ischaemia, responded well to the introduction of a cocktail of stem cell types.
As the ability of co-culture systems to regenerate native tissues expands, they are becoming a gold standard in the tissue engineering of complex tissue. The next phases of the exercise is one that will involve the integration of technologies such as bio-printing, with co-culture technology. As regenerative systems that can build tissues, and ultimately organs, the ability to replace damaged tissues will be a possibility in the future.
Stem cell co-culture and their applications have shown great promise in their testing conditions, and also in their applications. As they are utilized in tissue engineering applications, the ability to regenerate systems will be enhanced. As a patient, one of the things that you can feel confident about is the possibilities that exist for your healing. Research where you can about whether you feel that stem cell therapies are right for you, and consider them as part of your current or future therapies.
 Advances in tissue engineering through stem cell-based co-culture: https://onlinelibrary.wiley.com/doi/epdf/10.1002/term.1870