MSCs are an adult stem cell found in a wide range of human tissues, including bone marrow, adipose tissue (fat), placenta and umbilical cord blood. They are ‘multipotent’ – which means they can produce more than one type of cell. For example, they can differentiate into cartilage cells, bone cells and fat cells.
MSCs have been shown to facilitate regeneration and effects on the immune system without relying upon engraftment – in other words, the MSCs themselves do not become incorporated into the host, rather they exert their effects and are then eliminated within a short period of time.
MSCs are at the forefront of a new generation of treatments being investigated for a wide range of diseases including heart disease, GvHD, osteoarthritis and stroke. They are the most widely studied type of adult stem cells and there are currently over 850 clinical trials in progress using MSCs.
There has been extensive interest in the development of MSCs as therapeutic products, in particular because of their ability to modulate the immune system. They also secrete bioactive molecules such as cytokines, chemokines and growth factors, which has resulted in these cells being dubbed “drug factories” or “medicine secreting cells”.
MSCs can be either autologous (patient is treated with their own cells) or allogeneic (cells from a donor are used to treat other people). Allogeneic MSCs have not been shown to cause immune reactions in other people, so they can be used in an “off the shelf” manner, without any requirement for matching the donor to the recipient. This has important commercial advantages and many biotechnology companies have focussed on allogeneic rather than autologous MSCs.
Unlike Cynata’s Cymerus™ technology, first generation methods to manufacture MSC-based products rely on the isolation of MSCs from donated tissue (for example bone marrow, fat or placenta), followed by “culture expansion”.
When cells are culture expanded, the total number of cells increases as a result of the process of cell division. Thus, one cell gives rise to two, then two to four, and so on.
The difficulties of using MSCs derived from donor tissue in creating therapeutic products are that:
This means that each tissue donation can produce only a limited number of MSC doses, so a continuous supply of new donors would be needed to facilitate manufacturing at commercial scale.
There are significant logistical challenges and costs associated with collecting tissue donations. Firstly, it is likely to be difficult to find sufficient numbers of suitable donors to meet large scale commercial demand, particularly with donation procedures that are potentially risky, painful and invasive such as bone marrow harvesting. Secondly, the process of screening and testing multiple donors, followed by collecting and testing the donated material, is both time consuming and expensive.
Another problem with relying on a continuous supply of new donors is that changing the starting material is likely to change the characteristics of the end product – it has been shown that the number and quality of MSCs that can be isolated from different donations varies substantially. Thus, a cardinal requirement of manufacture of therapeutic products - the ability to manufacture the product consistently - cannot be assured when the process relies on different donors, or even the same donor across different donations.
With biological products, when the starting material is changed, regulatory authorities require evidence of “comparability”, which means proof that the final product does not change. Comparability testing with this type of product is a very complex, time consuming and costly process, and successful demonstration of comparability is far from guaranteed. In the event that comparability testing fails, the MSCs manufactured from the new donation would be classified as a different product, and commercial supply that new product would not be permitted under the regulatory approval for the original product. Consequently, it is extremely expensive to manufacture MSC products using processes that rely on a continuous supply of tissue donations, and there is a significant risk of supply constraint or interruption.
Cynata’s Cymerus platform overcomes the difficulties associated with manufacture of MSCs at scale. Read more about our platform.