In a promising development for treating joint conditions such as osteoarthritis, researchers have artificially produced human type II collagen, a key component of cartilage, for the first time. They have shown that it can slow the progress of osteoarthritis in rodents and relieve symptoms in people.
There is no cure for painful and debilitating joint conditions such as osteoarthritis and rheumatoid arthritis, that degrade cartilage in joints. Sufferers are usually given medication to lessen the pain and devices to support affected joints. If their condition worsens, they may undergo costly joint replacements involving invasive surgery that takes months to fully recover from. New treatments for osteoarthritis and rheumatoid arthritis based on stem cells are beginning to emerge, but these are prohibitively expensive.
“After the age of about 15, people lose their ability to produce type II collagen,” explains Hong-Lin Su of the National Chung Hsing University in Taichung, Taiwan. “That’s why degeneration of cartilage is such a serious problem.”
Now, Su, Chia-Ying Hsieh, who is at DuoGenic StemCells Corporation, and their co-workers have produced type II collagen artificially, by co-opting a certain type of immune cell known as monocytes to become M2 macrophages.
Macrophages detect and destroy foreign cells and also recruit other immune cells to the fray. They come in different types, which have different effects on osteoarthritis: M1 macrophages increase joint inflammation, making osteoarthritis worse, whereas M2 macrophages ease the symptoms of osteoarthritis by reducing inflammation.
The modified M2 macrophages in turn made type II collagen. When the team gave the cultured cells to mice with arthritic-like conditions, their symptoms were relieved.
“This ability to artificially induce type II collagen in other cells is unique,” says Su.
There was an element of serendipity involved in the discovery. “We weren’t actually setting out to do this; we were trying to produce dendritic cells that produce type I collagen from monocytes for tissue repair” says Hsieh. “But, to our surprise, we discovered that it turned into M2 macrophages and it also produced type II collagen.”
The team has taken this work further. In a recent open-labeled clinical study, they found that people with osteoarthritis in their knees exhibited milder symptoms on being treated with enriched peripheral blood mononuclear cells. The secret to the team’s success was creating a cocktail that stimulated the production of type II collagen. “We designed a special culture environment that can prime monocytes prone to M2 macrophages,” explains Su.
Reference:
Wang, F.-H. et al. Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells. Scientific Reports 12, 21663 (2022). https://doi.org/10.1038/s41598-022-25764-4
For further reference:
Chuang, C.-H. et al. Enriched peripheral blood-derived mononuclear cells for treating knee osteoarthritis. Cell Transplantation 32 (2023). https://doi.org/10.1177/09636897221149445
Hong-Lin Su’s research interests are stem cells, nanomedicine, and translational medicine. He is a veterinarian and obtained a PhD in the field of viral and host interaction from National Defense Medical Center Taiwan. Under the supervision of Professor Yoshiki Sasai in the Center for Developmental Biology (now the Center for Biosystems Dynamics Research) at RIKEN in Japan, he studied neural differentiation from pluripotent stem cells. He is a professor in the Department of Life Sciences at National Chung Hsing University and a National Innovation Award winner in Taiwan. As a founder of DuoGenic StemCells Corporation, he devotes himself to developing affordable cell therapy, including peripheral blood cell purification technology and an efficient cell expansion platform in cell culture bags.
Chia-Ying Hsieh’s research areas include stem cells, cell therapy, and advanced medical devices. She studied biology at National Tsing Hua University in Hsinchu, Taiwan, and biomedical engineering at National Taiwan University in Taipei, Taiwan. She completed her Master’s degree in bone grafts for bone regeneration. She is a research engineer at DuoGenic StemCells Corporation, Taiwan. She is devoted to developing culture media for peripheral blood cells and designing on-site cell therapies for arthritis.
