2. Academic Validation
  3. De novo interleukin-10 production primed by Lactobacillus sakei CVL-001 amplifies the immunomodulatory abilities of mesenchymal stem cells to alleviate colitis

De novo interleukin-10 production primed by Lactobacillus sakei CVL-001 amplifies the immunomodulatory abilities of mesenchymal stem cells to alleviate colitis

  • Biomed Pharmacother. 2024 Dec 19:182:117745. doi: 10.1016/j.biopha.2024.117745.
Phuong Thao Nguyen 1,  Yoojin Seo 2,  Ji-Su Ahn 2,  Su-Jeong Oh 1,  Hee-Jeong Park 1,  Jeong Hyun Yu 1,  Seong Hui Kim 1,  Yunji Lee 1,  Ji Won Yang 2,  Jaejin Cho 3,  Min-Jung Kang 4,  Jong-Hwan Park 5,  Hyung-Sik Kim 6
Affiliations

Affiliations

  • 1 Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea; Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea; Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.
  • 2 Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.
  • 3 Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea; Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
  • 4 Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: kkang085@naver.com.
  • 5 Laboratory Animal Medicine, College of Veterinary Medicine, Animal Medical Institute, Chonnam National University, Gwangju 61186, Republic of Korea; NODCURE, Inc, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea. Electronic address: jonpark@jnu.ac.kr.
  • 6 Department of Oral Biochemistry; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea; Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea; Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, Republic of Korea. Electronic address: hskimcell@pusan.ac.kr.
PMID: 39705909 DOI: 10.1016/j.biopha.2024.117745
Abstract

Mesenchymal stem cells (MSCs) hold therapeutic promise for treating inflammatory bowel disease (IBD) owing to their immunomodulatory properties. Currently, pre-conditioning strategies with several beneficial agents have been applied to enhance the efficacy of MSCs in treating IBDs. Probiotics are increasingly acknowledged as supplemental therapy for IBD; however, their potential benefits in MSCs-based therapy remain largely unexplored. In this study, we hypothesized that pretreating MSCs with Lactobacillus sakei CVL-001 (L. sakei CVL-001), a representative probiotic strain, could improve their therapeutic effectiveness for IBD. In line with this hypothesis, we noted that pretreatment with L. sakei CVL-001 significantly induced IL-10 secretion in MSCs via the activation of the STAT3 signaling pathway. These primed MSCs reduced pro-inflammatory cytokine production in LPS/IFN-γ-treated macrophages and promoted an M2 phenotype, associated with immunoregulation and tissue repair, in undifferentiated macrophages. In addition, their conditioned media significantly reduced the proliferation capacity of Jurkat T cells and splenocytes, while the neutralization of IL-10 reversed these phenomena. Furthermore, MSCs treated with L. sakei CVL-001 mitigated inflammatory responses and promoted epithelial regeneration, leading to accelerated recovery from disease symptoms and improved survival rates compared to naive MSCs in a DSS-induced colitis mouse model. In conclusion, our findings suggest that probiotics, such as L. sakei CVL-001, can improve the therapeutic efficacy of MSCs for treating IBD.

Keywords

Immunomodulation; Inflammatory Bowel Disease; Lactobacillus sakei CVL-001; Mesenchymal Stem Cells; Regeneration.

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