A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus

Jong Seok Kim, Sang Ho Cha, Woo Sik Kim, Seung Jung Han, Seung Bin Cha, Hong Min Kim, Kee Woong Kwon, So Jeong Kim, Hong Hee Choi, Jienny Lee, Sangnae Cho, Won Jung Koh, Yeong Min Park, SungJae Shin

Research output: Contribution to journalArticle

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Abstract

Recent studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of acute inflammatory injury and bacterial pneumonia, but their therapeutic applications in mycobacterial infections have not been investigated. In this study, we demonstrated the use of MSCs as a novel therapeutic strategy against Mycobacterium abscessus (M. abscessus), which is the most drug-resistant and difficult-to-treat mycobacterial pathogen. The systemic intravenous injection of MSCs not only improved mouse survival but also enhanced bacterial clearance in the lungs and spleen. Additionally, MSCs enhanced IFN-γ, TNF-α, IL-6, MCP-1, nitric oxide (NO) and PGE 2 production and facilitated CD4 + /CD8 + T cell, CD11b high macrophage, and monocyte recruitment in the lungs of M. abscessus-infected mice. To precisely elucidate the functions of MSCs in M. abscessus infection, an in vitro macrophage infection system was used. MSCs caused markedly increased NO production via NF-κB activation in M. abscessus-infected macrophages cultured in the presence of IFN-γ. Inhibiting NO or NF-κB signaling using specific inhibitors reduced the antimycobacterial activity of MSCs. Furthermore, the cellular crosstalk between TNF-α released from IFN-γ-stimulated M. abscessus-infected macrophages and PGE 2 produced by MSCs was necessary for the mycobacterial-killing activity of the macrophages. Finally, the importance of increased NO production in response to MSC administration was confirmed in the mouse M. abscessus infection model. Our results suggest that MSCs may offer a novel therapeutic strategy for treating this drug-resistant mycobacterial infection by enhancing the bacterial-killing power of macrophages. Stem Cells 2016;34:1957–1970.

Original languageEnglish
Pages (from-to)1957-1970
Number of pages14
JournalStem Cells
Volume34
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1

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Mycobacterium
Mesenchymal Stromal Cells
Macrophages
Nitric Oxide
Therapeutics
Mycobacterium Infections
Prostaglandins E
Bacterial Pneumonia
Lung
Infection
Bacterial Infections
Intravenous Injections
Pharmaceutical Preparations
Monocytes
Interleukin-6
Stem Cells
Spleen
T-Lymphocytes
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Kim, Jong Seok ; Cha, Sang Ho ; Kim, Woo Sik ; Han, Seung Jung ; Cha, Seung Bin ; Kim, Hong Min ; Kwon, Kee Woong ; Kim, So Jeong ; Choi, Hong Hee ; Lee, Jienny ; Cho, Sangnae ; Koh, Won Jung ; Park, Yeong Min ; Shin, SungJae. / A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus. In: Stem Cells. 2016 ; Vol. 34, No. 7. pp. 1957-1970.
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abstract = "Recent studies have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of acute inflammatory injury and bacterial pneumonia, but their therapeutic applications in mycobacterial infections have not been investigated. In this study, we demonstrated the use of MSCs as a novel therapeutic strategy against Mycobacterium abscessus (M. abscessus), which is the most drug-resistant and difficult-to-treat mycobacterial pathogen. The systemic intravenous injection of MSCs not only improved mouse survival but also enhanced bacterial clearance in the lungs and spleen. Additionally, MSCs enhanced IFN-γ, TNF-α, IL-6, MCP-1, nitric oxide (NO) and PGE 2 production and facilitated CD4 + /CD8 + T cell, CD11b high macrophage, and monocyte recruitment in the lungs of M. abscessus-infected mice. To precisely elucidate the functions of MSCs in M. abscessus infection, an in vitro macrophage infection system was used. MSCs caused markedly increased NO production via NF-κB activation in M. abscessus-infected macrophages cultured in the presence of IFN-γ. Inhibiting NO or NF-κB signaling using specific inhibitors reduced the antimycobacterial activity of MSCs. Furthermore, the cellular crosstalk between TNF-α released from IFN-γ-stimulated M. abscessus-infected macrophages and PGE 2 produced by MSCs was necessary for the mycobacterial-killing activity of the macrophages. Finally, the importance of increased NO production in response to MSC administration was confirmed in the mouse M. abscessus infection model. Our results suggest that MSCs may offer a novel therapeutic strategy for treating this drug-resistant mycobacterial infection by enhancing the bacterial-killing power of macrophages. Stem Cells 2016;34:1957–1970.",
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Kim, JS, Cha, SH, Kim, WS, Han, SJ, Cha, SB, Kim, HM, Kwon, KW, Kim, SJ, Choi, HH, Lee, J, Cho, S, Koh, WJ, Park, YM & Shin, S 2016, 'A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus', Stem Cells, vol. 34, no. 7, pp. 1957-1970. https://doi.org/10.1002/stem.2353

A Novel Therapeutic Approach Using Mesenchymal Stem Cells to Protect Against Mycobacterium abscessus. / Kim, Jong Seok; Cha, Sang Ho; Kim, Woo Sik; Han, Seung Jung; Cha, Seung Bin; Kim, Hong Min; Kwon, Kee Woong; Kim, So Jeong; Choi, Hong Hee; Lee, Jienny; Cho, Sangnae; Koh, Won Jung; Park, Yeong Min; Shin, SungJae.

In: Stem Cells, Vol. 34, No. 7, 01.07.2016, p. 1957-1970.

Research output: Contribution to journalArticle

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AU - Kim, Hong Min

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AU - Choi, Hong Hee

AU - Lee, Jienny

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AU - Koh, Won Jung

AU - Park, Yeong Min

AU - Shin, SungJae

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