Stem cells are up-and-coming therapies, and a major engineering problem has been scaling up the cell manufacturing to create enough cells for different therapeutic applications. Cytotwister, from the Industrial Technology Research Institute (ITRI) in Taiwan, makes a step towards solving that with a unique 3D stem cell bioreactor system that addresses common issues in stem cell harvesting and recovery. Their innovative device was a finalist for the R&D 100 Awards. We spoke with Dr. Hsin-Hsin Shen, Director of ITRI’s Regenerative Medicine Technologies Division about the Cytotwister, how it works, and how it will help medicine.
Ben Ouyang, Medgadget: What’s Cytotwister?
Dr. Hsin-Hsin Shen, ITRI: Cytotwister is a bioreactor system. From the outside, it looks like a cell culture bioreactor, but the unique difference is the matrix design for cell attachment. We have a proprietary 3D matrix that can be easily deconstructed by twisting the structure to allow the cells to be easily harvested more smoothly than typical 3D culture systems. The most important part is this matrix. The matrix formulation’s proprietary structure and surface modification technology using chemicals and peptides allows MSCs to attach well, proliferate efficiently, and be easily harvested. Each reactor is single use and can expand the original stem cells 10,000 times in two to three weeks. It automatically monitors the pH, temperature, glucose during this time and collects the data. It corrects by flowing fresh media into the reactor. We also use a serum-free media design because it allows the adipose-derived MSCs to be derived more efficiently. We have licensed to Taiwan’s company to sell this media to larger medical centres for research and clinical development two years ago.
Medgadget: What’s unique about the harvesting system?
Dr. Hsin-Hsin Shen: In traditional 3D cultures, we need to use chemicals and enzymes to reach the inner part of the matrices and treat the cells to disrupt the cell-cell and cell-surface interactions and detach them. But they cannot do this efficiently because enzyme penetration to the core of the matrix is shallow, or the enzyme is inhibited by the conditions or matrix itself. So we use a physical twisting and pulling to destroy the culture matrix and pull out the core to allow the inner cells to be more easily accessible to enzymes for detachment.
Medgadget: What is the current application for Cytotwister?
Dr. Hsin-Hsin Shen: Mesenchymal stem cells (MSCs) are currently used for research only but we’ve tried some applications for Cytotwister. We’re in an ongoing process to receive approval. In dog and cat therapy, we now have clinical approval and have helped about 10 dogs to help derive dog-derived MSCs to cure them of their bone degeneration. In pets, we can use 1 gram of fat from a younger dog (<3 years old) to make 100,000 treatments for pets, with each treatment being more than 1 billion cells. We use an allogenic treatment, and it takes us two to three weeks to complete this treatment.
Medgadget: Who else uses stem cell bioreactors?
Dr. Hsin-Hsin Shen: Corning has a mesenchymal stem cell culturing system, but uses a layer by layer culturing method that uses lots of media and resources. Most companies use the layer by layer to stack their cells and do not use the construction/deconstruction method to culture and collect cells.
Medgadget: What are your plans for use in humans?
Dr. Hsin-Hsin Shen: In pets we can already use our system. In human use, we must first go through clinical trials, which we plan in 3-5 years.
Link: ITRI’s press release…
