CD317 MSCs Expanded with Chemically Defined Media Have Enhanced Immunological Anti-inflammatory Activities

Overview

Journal Stem Cell Res Ther

Publisher Biomed Central

Date 2024 Jan 3

PMID 38169422

Authors

Jun Song

Qi Ma

Yumeng Li

Xianqi Wang

Si Chen

Bowei Liang

Xiaoqi Lin

Jieting Chen

Shiru Xu

Shaoquan Shi

Jingting Zhang

Lianghui Diao

Yong Zeng

Jianyong Xu

Affiliations

Soon will be listed here.

Abstract

Background: Although both preclinical and clinical studies have shown the great application potential of MSCs (mesenchymal stem/stromal cells) in treating many kinds of diseases, therapeutic inconsistency resulting from cell heterogeneity is the major stumbling block to their clinical applications. Cell population diversity and batch variation in the cell expansion medium are two major inducers of MSC heterogeneity.

Methods: Cell population diversity was investigated through single-cell RNA sequencing analysis of human MSCs derived from the umbilical cord and expanded with fully chemically defined medium in the current study. Then, the MSC subpopulation with enhanced anti-inflammatory effects was studied in vitro and in vivo.

Results: Our data showed that MSCs contain different populations with different functions, including subpopulations with enhanced functions of exosome secretion, extracellular matrix modification and responses to stimuli (regeneration and immune response). Among them, CD317 MSCs have improved differentiation capabilities and enhanced immune suppression activities. Underlying mechanism studies showed that higher levels of TSG6 confer enhanced anti-inflammatory functions of CD317 MSCs.

Conclusions: Thus, CD317 MSCs might be a promising candidate for treating immunological disorder-related diseases.

Citing Articles

Enhanced myofibroblast differentiation of eMSCs in intrauterine adhesions.

Song J, Li M, Tao Y, Li Y, Mai C, Zhang J Stem Cell Res Ther. 2025; 16(1):35.

PMID: 39901307 PMC: 11792338. DOI: 10.1186/s13287-025-04183-y.

Improved therapeutic consistency and efficacy of CD317 MSCs through stabilizing TSG6 by PTX3.

Shi S, Chen S, Liang B, Li Y, Ma Q, Li M Stem Cell Res Ther. 2024; 15(1):92.

PMID: 38539221 PMC: 10976765. DOI: 10.1186/s13287-024-03706-3.

References

Wynn R, Hart C, Corradi-Perini C, ONeill L, Evans C, Wraith J . A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood. 2004; 104(9):2643-5. DOI: 10.1182/blood-2004-02-0526. View

Jiang W, Xu J . Immune modulation by mesenchymal stem cells. Cell Prolif. 2019; 53(1):e12712. PMC: 6985662. DOI: 10.1111/cpr.12712. View

Li L, Yang L, Chen X, Chen X, Diao L, Zeng Y . TNFAIP6 defines the MSC subpopulation with enhanced immune suppression activities. Stem Cell Res Ther. 2022; 13(1):479. PMC: 9509641. DOI: 10.1186/s13287-022-03176-5. View

Freeman B, Jung J, Ogle B . Single-Cell RNA-Seq of Bone Marrow-Derived Mesenchymal Stem Cells Reveals Unique Profiles of Lineage Priming. PLoS One. 2015; 10(9):e0136199. PMC: 4564185. DOI: 10.1371/journal.pone.0136199. View

Kuci S, Kuci Z, Kreyenberg H, Deak E, Putsch K, Huenecke S . CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica. 2010; 95(4):651-9. PMC: 2857196. DOI: 10.3324/haematol.2009.015065. View

Tian J, Kou X, Wang R, Jing H, Chen C, Tang J . Autophagy controls mesenchymal stem cell therapy in psychological stress colitis mice. Autophagy. 2020; 17(9):2586-2603. PMC: 8496723. DOI: 10.1080/15548627.2020.1821547. View

Pinho S, Lacombe J, Hanoun M, Mizoguchi T, Bruns I, Kunisaki Y . PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J Exp Med. 2013; 210(7):1351-67. PMC: 3698522. DOI: 10.1084/jem.20122252. View

Krampera M, Le Blanc K . Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy. Cell Stem Cell. 2021; 28(10):1708-1725. DOI: 10.1016/j.stem.2021.09.006. View

Zhang S, Fang J, Liu Z, Hou P, Cao L, Zhang Y . Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis. Stem Cell Res Ther. 2021; 12(1):50. PMC: 7796621. DOI: 10.1186/s13287-020-02118-3. View

10.

Gu G, Lv X, Liu G, Zeng R, Li S, Chen L . Tnfaip6 Secreted by Bone Marrow-Derived Mesenchymal Stem Cells Attenuates TNBS-Induced Colitis by Modulating Follicular Helper T Cells and Follicular Regulatory T Cells Balance in Mice. Front Pharmacol. 2021; 12:734040. PMC: 8542666. DOI: 10.3389/fphar.2021.734040. View

11.

Horie S, Masterson C, Brady J, Loftus P, Horan E, OFlynn L . Umbilical cord-derived CD362 mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy. Stem Cell Res Ther. 2020; 11(1):116. PMC: 7071745. DOI: 10.1186/s13287-020-01624-8. View

12.

Xu J, Lian W, Chen J, Li W, Li L, Huang Z . Chemical-defined medium supporting the expansion of human mesenchymal stem cells. Stem Cell Res Ther. 2020; 11(1):125. PMC: 7083066. DOI: 10.1186/s13287-020-01641-7. View

13.

Soliman H, Theret M, Scott W, Hill L, Underhill T, Hinz B . Multipotent stromal cells: One name, multiple identities. Cell Stem Cell. 2021; 28(10):1690-1707. DOI: 10.1016/j.stem.2021.09.001. View

14.

Tiwari R, de la Torre J, McGavern D, Nayak D . Beyond Tethering the Viral Particles: Immunomodulatory Functions of Tetherin (). DNA Cell Biol. 2019; 38(11):1170-1177. PMC: 6939588. DOI: 10.1089/dna.2019.4777. View

15.

Shin T, Kim H, Kang T, Lee B, Lee H, Kim Y . Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis. Cell Death Dis. 2016; 7(12):e2524. PMC: 5260999. DOI: 10.1038/cddis.2016.442. View

16.

Hoang D, Pham P, Bach T, Ngo A, Nguyen Q, Phan T . Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022; 7(1):272. PMC: 9357075. DOI: 10.1038/s41392-022-01134-4. View

17.

Costa L, Eiro N, Fraile M, Gonzalez L, Saa J, Garcia-Portabella P . Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses. Cell Mol Life Sci. 2020; 78(2):447-467. PMC: 7375036. DOI: 10.1007/s00018-020-03600-0. View

18.

Xu J, Chen J, Li W, Lian W, Huang J, Lai B . Additive Therapeutic Effects of Mesenchymal Stem Cells and IL-37 for Systemic Lupus Erythematosus. J Am Soc Nephrol. 2019; 31(1):54-65. PMC: 6935004. DOI: 10.1681/ASN.2019050545. View

19.

Georgakis M, Bernhagen J, Heitman L, Weber C, Dichgans M . Targeting the CCL2-CCR2 axis for atheroprotection. Eur Heart J. 2022; 43(19):1799-1808. DOI: 10.1093/eurheartj/ehac094. View

20.

Dunn C, Kameishi S, Grainger D, Okano T . Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies. Acta Biomater. 2021; 133:114-125. DOI: 10.1016/j.actbio.2021.03.069. View