AUTOSTEM brings together several important technical innovations, which will enable the automated production of stem cells.
- The collection (aspiration) of bone marrow from donors is the first step in the cell production process. Typically, this process involves the manual suction of bone marrow from within the donor’s pelvis (the iliac crest),using a large-bore syringe. The process is quite painful; relatively few donors repeat the process (in contrast, for example, with blood donation, where repeat donors are central to blood supplies). Within AUTOSTEM, Irish SME Crospon is developing a novel device for marrow aspiration, that uses a gentle, consistent vacuum-pump pressure to collect marrow with the minimum donor discomfort. The new device will be designed, built and CE-marked during the project.
- The isolation of stem cells from bone marrow will use antibody-activated carrier surfaces within a ‘seeding’ bio-reactor. Within a bio-reactor, cells adhere to the internal surface, and to the surface of carriers within the reactor, as part of the colony formation and culturing process. By coating these surfaces with patented antibodies from partner Orbsen Therapeutics, stem cells will adhere to the surfaces, while other forms of cells will not.
- Having isolated the stem cells, the next step is to culture them, to generate large numbers of cells. This takes place in a second ‘expander’ bioreactor. Several different bioreactor technologies exist, and will be assessed during AUTOSTEM. These include Zellwerk’s rotating-disk ZRP bioreactor, as well as stirred and wave bio-reactors, from AS. The bioreactor/carrier combination that produces the highest quantity and quality of stem cells will be selected, and included in the automated pipeline.
- Within the bio-reactor, the cells are fed using a cell culture medium. Typical media include fetal bovine serum (FBS), a product made from the blood of unborn calves. The world supply of FBS is limited, because only FBS from Australia and New Zealand is certified to be BSE-free. However, in AUTOSTEM, we will use a novel FBS-free medium, developed by partners NUI Galway. Research has shown that the quantity and quality of cells produced using this FBS-free medium are both better than when common FBS-containing medium is used.
- Monitoring the cell culture conditions within the bioreactor is essential if output is to be maximised, and if cell quality is to be maintained. Variables such as temperature, pH, dissolved oxygen, etc. must be monitored, so that adjustments can be made in real-time, to keep the cell environment optimal. Partners Tyndall-UCC will develop a new sensor platform, to be integrated within the expansion bioreactor, which will enable real-time monitoring and environmental control.
- The robotic pipeline is itself an important innovation. Building on earlier work by partners Fraunhofer IPT, the pipeline includes a mobile robotic arm, which moves, cells and other materials from one step of the pipeline to another, and which enables real-time sampling and quality control. A full process control software platform links the various steps together, including inputs from the sensors, cell culture parameters set by the operators, etc. The pipeline is entirely enclosed in a sterile environment, without any manual operations.
- Following cell harvesting, freezing, and delivery to the clinic, a final innovation is deployed. This is a combined thaw-and-infuse device (again developed by Crospon, with intellectual property from NUI Ga
lway), which reduces the number of steps that the physician or clinical staff must carry out, and maintains quality and consistency of cell product and delivery. For greater patient comfort, a gentle pump once again replaces manual syringe infusion at the site of cell delivery.