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
  • 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. [email protected].
  • 10. Department of Occupational Therapy, Asia University, Taichung, Taiwan. [email protected].
  • 11. Department of Life Sciences, National Chung Hsing University, 145, Xin-Da Rd., South Dist., Taichung City, 402, Taiwan. [email protected].
  • # Contributed equally.
PMID: 36522405 DOI: 10.1038/s41598-022-25764-4
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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