Bone marrow-derived humoral factors suppress oxidative phosphorylation, upregulate TSG-6, and improve therapeutic effects on liver injury of mesenchymal stem cells

Mesenchymal stem cells, which have the potential to be used in regenerative medicine, require improvements in quality for patient use. To maintain stemness of cultured bone marrow-derived mesenchymal stem cells, we focused on the bone marrow microenvironment, generated a conditioned medium of whole...

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Bibliographic Details
Published in:Journal of Clinical Biochemistry and Nutrition 2020, Vol.66(3), pp.213-223
Main Authors: Miyaji, Takashi, Takami, Taro, Fujisawa, Koichi, Matsumoto, Toshihiko, Yamamoto, Naoki, Sakaida, Isao
Format: Article
Language:English
Subjects:
Bone marrow
Carbon tetrachloride
Hepatocytes
Hypoxia
Hypoxia-inducible factor 1
Hypoxia-inducible factor 1a
Hypoxia-inducible factors
Liver
liver disease
Liver diseases
mesenchymal stem cell
Mesenchymal stem cells
microRNA
MicroRNAs
miRNA
Mitochondria
Original
Oxidative phosphorylation
Pathogenesis
Phosphorylation
Regenerative medicine
Stem cell transplantation
Stem cells
Suppressors
TNF-stimulated gene 6
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Summary:Mesenchymal stem cells, which have the potential to be used in regenerative medicine, require improvements in quality for patient use. To maintain stemness of cultured bone marrow-derived mesenchymal stem cells, we focused on the bone marrow microenvironment, generated a conditioned medium of whole bone marrow cells (BMC-CM), and assessed its effects on bone marrow-derived mesenchymal stem cells. BMC-CM suppressed morphological deterioration and proliferative decline in cultured bone marrow-derived mesenchymal stem cells, suppressed mitochondrial oxidative phosphorylation activity, a stemness indicator, and upregulated suppressors of oxidative phosphorylation such as hypoxia-inducible factor-1 alpha, Sirtuin 3, 4, and 5. Furthermore, BMC-CM upregulated TNF-stimulated gene 6 and ameliorated the therapeutic effects of cells on liver injury in carbon tetrachloride-administered rats. Since the elimination of 20–220-nm particles attenuated the effects of BMC-CM, we further analyzed exosomal microRNAs produced by whole bone marrow cells. Among the 49 microRNAs observed to be upregulated during the preparation of BMC-CM, several were identified that were associated with suppression of oxidative phosphorylation, upregulation of TNF-stimulated gene 6, and the pathogenesis of liver diseases. Thus, bone marrow-derived humoral factors including exosomal microRNAs may help to improve the therapeutic quality of bone marrow-derived mesenchymal stem cells for liver regenerative therapy.
ISSN:0912-0009
1880-5086
DOI:10.3164/jcbn.19-125