1. Academic Validation
  2. Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells

Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells

  • Sci Rep. 2022 Dec 15;12(1):21663. doi: 10.1038/s41598-022-25764-4.
Fu-Hui Wang # 1 Chia-Ying Hsieh # 1 Ching-I Shen 1 Chang-Han Chuang 2 3 4 Yu-Hsuan Chung 2 3 4 Chi-Chung Kuo 5 6 Kuan-Der Lee 7 8 Chih-Lung Lin 9 10 Hong-Lin Su 11
Affiliations

Affiliations

  • 1 Duogenic StemCells Corporation, Taichung, Taiwan.
  • 2 Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan.
  • 3 National Chung Hsing University, Taichung, Taiwan.
  • 4 Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
  • 5 Department of Neurology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
  • 6 School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
  • 7 Department of Medical Research and Cell Therapy and Regenerative Medicine Center, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 8 Department of Medicine and Center for Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 9 Department of Neurosurgery, Asia University Hospital, 222, Fuxin Rd., Wufeng Dist., Taichung City, Taiwan. jefflin0529@gmail.com.
  • 10 Department of Occupational Therapy, Asia University, Taichung, Taiwan. jefflin0529@gmail.com.
  • 11 Department of Life Sciences, National Chung Hsing University, 145, Xin-Da Rd., South Dist., Taichung City, 402, Taiwan. suhonglin@nchu.edu.tw.
  • # Contributed equally.
Abstract

The human type II collagen (Col II), specifically expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artificial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purified and were treated with high doses of macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), or granulocyte-colony stimulating factor (G-CSF) and examined the Col II expression at indicated days. Quantitative Col II expression was validated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and flow cytometry. We demonstrate that monocytes in PBMNCs can be artificially induced to express both Col II proteins and M2 macrophage markers by the high concentration of colony-stimulating factors, especially M-CSF and GM-CSF. The Col II proteins were detected on the cell membrane and in the cytoplasm by flow cytometry and immunocytostaining. Combination with IL-4 provided a synergistic effect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double-expressing cells, named modified macrophages, share M2 macrophages' anti-inflammatory potency. We demonstrated that the modified macrophages could significantly attenuate the inflammatory progress of Complete Freund's Adjuvant (CFA)-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the first evidence that a modified macrophage population could ectopically express Col II and control the progress of arthritis in Animals.

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