Development and evaluation of IL‐6 overexpressing mesenchymal stem cells (MSCs)
Open accessAbstract
Mesenchymal stem/stromal cell (MSC) therapy has been investigated in multiple diseases and conditions. Although the mechanisms of MSC-based therapies are not fully understood, we and others have shown interleukin 6 (IL-6) to be an important factor in MSC function. IL-6 contributes to many biological events, such as immune response, neurogenesis, and bone remodeling. In our study, we tested the feasibility of engineering MSCs by IL-6 mRNA transfection (eMSCs-IL6) and evaluated the optimal time to harvest them after transfection. We then assessed the functional characteristics of eMSCs-IL6. Quantitative real-time PCR and ELISA results have shown that mature IL-6 mRNA was efficiently transfected into MSCs using a lipofectamine based method. The IL-6 mRNA and protein overexpression peaked after 1 day of transfection and the secreted IL-6 protein was sustained for at least 6 days. A short time course experiment demonstrated that 4 h after transfection was the best time point to harvest and freeze eMSCs-IL6 for future studies. In addition, eMSCs-IL6 maintained their characteristics as defined by International Society for Cell & Gene Therapy. The immunosuppressive capacity of conditioned culture medium (CCM) from eMSCs-IL6 (CCM-IL6) was significantly enhanced compared to naïve MSCs conditioned culture medium (CCM-control). Our studies established for the first time the feasibility of efficiently generating IL-6 overexpressing MSCs which have enhanced immunosuppressive capacity. This is providing a novel approach to improve the efficacy of MSCs for potential application in regenerative medicine.
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TNF-α has a stimulating effect on bone resorption but an inhibitory effect on bone formation.
“TNF-α, such as IL-6, has a stimulating effect on bone resorption but an inhibitory effect on bone formation [84, 85]”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [84]
The Introduction mentions IL-6's involvement in bone remodeling, but does not describe effects on bone resorption or formation. Searches for TNF-α, tumor necrosis factor, bone resorption, and bone formation found no passage in our copy addressing the attributed claim. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIL-6 acts as an osteoblast inhibitor and promotes osteoclast formation.
“IL-6 acts as an osteoblast inhibitor and promotes osteoclast formation [84]”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [84]
The Introduction says IL-6 is involved in bone remodeling, but does not describe its effects on osteoblasts or osteoclast formation. Searches for osteoblast inhibition and osteoclast formation found no passage in our copy addressing those effects. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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- Authors
- Huang, P., Zhang, C., Delawary, M., Korchak, J. A., Suda, K., & Zubair, A. C.
- Affiliations
- Mayo Clinic in Florida (US)
- Daiichi-Sankyo (Japan) (JP)
- Corresponding author
- Zubair, Abba C.
- Venue
- Journal of Tissue Engineering and Regenerative Medicine
- Publisher
- Wiley
- Published
- 2021-12-19
- Volume
- 16
- Issue
- 3
- Pages
- 244-253
- ISSN
- 1932-6254 (ISSN-L)
- 1932-7005
- OpenAlex
- W4200455409
- Cited by
- 15
- References
- 27
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 2
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Tissue Engineering and Regenerative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- Daiichi Sankyo Company
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, interleukin-6, transfection, lipofectamine, conditioned medium, stem cell engineering, regenerative medicine
- MeSH terms
- RNA, Messenger, Interleukin-6, Culture Media, Conditioned, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Cell- and Tissue-Based Therapy
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