Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway

Atsuta Ikiru, Shiyu Liu, Yasuo Miura, Kentaro Akiyama, Chider Chen, Ying An, Songtao Shi, Fa Ming Chen

Research output: Contribution to journalArticle

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Abstract

Introduction. Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases traditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue damage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone disease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and metastasis. Methods. In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of intravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether Fas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells. Results: In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-Lhigh MSCs) showed remarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting tumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys. In addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with Fas-Lhigh MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced apoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells. In contrast, Fas-L null MSCs promote MM growth. Conclusions: These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based inhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the levels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth.

Original languageEnglish
Article number111
JournalStem Cell Research and Therapy
Volume4
Issue number5
DOIs
Publication statusPublished - Sep 13 2013

Fingerprint

Fas Ligand Protein
Stem cells
Multiple Myeloma
Mesenchymal Stromal Cells
Growth
Apoptosis
Tumors
Bone
Neoplasms
Neoplasm Metastasis
Cell growth
Bone Diseases
Bone Resorption
Cell- and Tissue-Based Therapy
Coculture Techniques
Autoimmunity
Assays
Survival Rate

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Cite this

Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway. / Ikiru, Atsuta; Liu, Shiyu; Miura, Yasuo; Akiyama, Kentaro; Chen, Chider; An, Ying; Shi, Songtao; Chen, Fa Ming.

In: Stem Cell Research and Therapy, Vol. 4, No. 5, 111, 13.09.2013.

Research output: Contribution to journalArticle

Ikiru, Atsuta ; Liu, Shiyu ; Miura, Yasuo ; Akiyama, Kentaro ; Chen, Chider ; An, Ying ; Shi, Songtao ; Chen, Fa Ming. / Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway. In: Stem Cell Research and Therapy. 2013 ; Vol. 4, No. 5.
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abstract = "Introduction. Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases traditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue damage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone disease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and metastasis. Methods. In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of intravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether Fas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells. Results: In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-Lhigh MSCs) showed remarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting tumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys. In addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with Fas-Lhigh MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced apoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells. In contrast, Fas-L null MSCs promote MM growth. Conclusions: These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based inhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the levels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth.",
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