Cell therapies are a rapidly developing area of medicine where stem cells offer the potential to repair human tissue and maintain organ function in chronic diseases. However, a major obstacle with translating successful research into actual products and treatments is how to mass-produce these complex living materials.
 
Cynata Therapeutics recently achieved a major manufacturing milestone for stem cells and is now able to scale up manufacture of its mesenchymal stem cells (MSCs) for therapeutic use. The company’s platform technology, Cymerus, has been successfully validated at Waisman Biomanufacturing in Madison, WI, confirming this stem cell manufacturing process is capable of producing MSCs for therapeutic application, consistently and efficiently, in a GMP production environment.
 
What makes this process efficient is the Cymerus technology, which uses an effectively limitless starting material — a bank of induced pluripotent stem cells (iPSCs) — and a process to derive MSCs for commercial use, whereas other methods require a continuous supply of new tissue donations. Cynata expects to be able to produce all of the MSCs it will need from a single iPSC bank, derived from a single blood donation, significantly reducing costs.
 
The company can now manufacture its GMP-grade Cymerus MSC product for its clinical trial and collaboration programs. A Phase I trial of the Cymerus stem cell technology will examine the impact of these manufactured cells on patients affected by graft-versus-host disease (GvHD), a condition that often follows a bone marrow transplant.
 
Dr. Ross Macdonald, chief executive officer of Cynata Therapeutics, discuses the technology behind the Cymerus process, how it works, and its broad therapeutic applications. －KB
 
Contract Pharma: What are the main obstacles to manufacturing stem cells on a large scale? 

Ross Macdonald: Existing methods to manufacture mesenchymal stem cells (MSCs) rely on a couple of factors. One is extracting the MSCs from bone marrow, adipose tissue or other sources provided by donors. The second is, since MSCs in such sources are very scarce, the material extracted needs to be expanded in cell culture. This introduces substantial uncertainty into the eventual finished product as MSCs have been shown to senesce or age when expanded. Moreover, multiple donors are required, meaning further variability in the eventual finished product. Cynata’s Cymerus technology overcomes these problems.
 
CP: Please briefly explain what induced pluripotent stem cells (iPSCs) are and how they are mass produced? 
 
RM: An ipsc is a cell derived from a donor that has been reprogrammed to a pluripotent state. As such, it is capable both of infinite self-renewal (expansion) and of being differentiated into a functional cell type, e.g. an MSC. They are expanded in cell culture, allowing production on a mass (industrial) scale.
 
CP: How is large scale manufacturing achieved through the Cymerus process? 
 
RM: The starting material for Cynata’s Cymerus MSCs is an IPS cell. Since this cell is capable of infinite self-renewal it forms an essentially limitless starting material, avoiding the need to continually source donor-derived material.
 
CP: What are the regulatory challenges associated with manufacturing stem cells and scale-up? 
 
RM: Like any pharmaceutical product, Cynata will have to demonstrate that its Cymerus MSCs are safe and effective, and that production can occur in a controlled, consistent and reproducible manner.
  
CP: What therapeutic areas are applicable to the Cymerus manufacturing process? 
 
RM: MSCs have been shown in clinical studies to be useful in a wide range of diseases including stroke, Crohn’s disease and myocardial infarction. It is expected that MSCs manufactured using the Cymerus process will have the same therapeutic utility as MSCs derived from sources such as bone marrow.

CP: What sort of response do you anticipate with respect to outsourcing services for this manufacturing platform? 
 
RM: We expect the announcement from Cynata to capture the attention of pharma and biotech companies seeking an MSC manufacturing solution that will enable them to enter this revolutionary market, with a consistent and reliable product, manufactured at a reasonable cost-of-goods margin.
 
Dr. Ross Macdonald has more than 20 years of experience and a track record of success in pharmaceutical and biotechnology businesses. His career history includes positions as Vice President of Business Development for Sinclair Pharmaceuticals Ltd., a UK-based specialty pharmaceutical company, and Vice President of Corporate Development for Stiefel Laboratories, which was acquired by GlaxoSmithKline in 2009. Dr. Macdonald has also served as CEO of Living Cell Technologies Ltd., Vice President of Business Development of Connetics Corp. and Vice President of R&D at F H Faulding & Co Ltd.