Mesenchymal Stem Cells in Homeostasis and Systemic Diseases: Hypothesis, Evidences, and Therapeutic Opportunities

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Aug 3

PMID 31370159

Citations 58

Authors

Francisco J Vizoso

Noemi Eiro

Luis Costa

Paloma Esparza

Mariana Landin

Patricia Diaz-Rodriguez

Jose Schneider

Roman Perez-Fernandez

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm "one disease, one drug".

Citing Articles

Identifying differentiation markers between dermal fibroblasts and adipose-derived mesenchymal stromal cells (AD-MSCs) in human visceral and subcutaneous tissues using single-cell transcriptomics.

Koczkowska M, Kostecka A, Zawrzykraj M, Myszczynski K, Skoniecka A, Deptula M Stem Cell Res Ther. 2025; 16(1):64.

PMID: 39934849 PMC: 11818286. DOI: 10.1186/s13287-025-04185-w.

MSC-microvesicles protect cartilage from degradation in early rheumatoid arthritis via immunoregulation.

Wei S, Cheng R, Li S, Lu C, Zhang Q, Wu Q J Nanobiotechnology. 2024; 22(1):673.

PMID: 39497131 PMC: 11536868. DOI: 10.1186/s12951-024-02922-6.

Mesenchymal Stem Cells and Their Derived Products in Ageing and Diseases.

Vizoso F, Costa L, Eiro N Int J Mol Sci. 2024; 25(13).

PMID: 39000084 PMC: 11241289. DOI: 10.3390/ijms25136979.

Murine bone-derived mesenchymal stem cells undergo molecular changes after a single passage in culture.

Hughes A, Kuek V, Oommen J, Kotecha R, Cheung L Sci Rep. 2024; 14(1):12396.

PMID: 38811646 PMC: 11137146. DOI: 10.1038/s41598-024-63009-8.

Emerging role of mesenchymal stem cells-derived extracellular vesicles in vascular dementia.

Liu Z, Cheng L, Zhang L, Shen C, Wei S, Wang L Front Aging Neurosci. 2024; 16:1329357.

PMID: 38389559 PMC: 10881761. DOI: 10.3389/fnagi.2024.1329357.

References

DiGirolamo C, Stokes D, Colter D, Phinney D, Class R, Prockop D . Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol. 1999; 107(2):275-81. DOI: 10.1046/j.1365-2141.1999.01715.x. View

Adkins D, Abidi M, BROWN R, Khoury H, Goodnough L, Vij R . Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy. Bone Marrow Transplant. 2001; 26(11):1239-41. DOI: 10.1038/sj.bmt.1702703. View

Papadaki H, Kritikos H, Gemetzi C, Koutala H, Marsh J, Boumpas D . Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: evidence for a tumor necrosis factor alpha-mediated effect. Blood. 2002; 99(5):1610-9. DOI: 10.1182/blood.v99.5.1610. View

Shi S, Gronthos S . Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003; 18(4):696-704. DOI: 10.1359/jbmr.2003.18.4.696. View

Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C . Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005; 289(1):F31-42. DOI: 10.1152/ajprenal.00007.2005. View

Price M, Chou C, Frantzen M, Miyamoto T, Kar S, Lee S . Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol. 2005; 111(2):231-9. DOI: 10.1016/j.ijcard.2005.07.036. View

Liu C, Hwang S . Cytokine interactions in mesenchymal stem cells from cord blood. Cytokine. 2005; 32(6):270-9. DOI: 10.1016/j.cyto.2005.11.003. View

Caplan A, Dennis J . Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006; 98(5):1076-84. DOI: 10.1002/jcb.20886. View

Wang M, Crisostomo P, Herring C, Meldrum K, Meldrum D . Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006; 291(4):R880-4. DOI: 10.1152/ajpregu.00280.2006. View

10.

Jiang W, Ma A, Wang T, Han K, Liu Y, Zhang Y . Intravenous transplantation of mesenchymal stem cells improves cardiac performance after acute myocardial ischemia in female rats. Transpl Int. 2006; 19(7):570-80. DOI: 10.1111/j.1432-2277.2006.00307.x. View

11.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

12.

Sun L, Zhang H, Feng X, Hou Y, Lu L, Fan L . Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007; 16(2):121-8. DOI: 10.1177/0961203306075793. View

13.

Hung S, Pochampally R, Chen S, Hsu S, Prockop D . Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells. 2007; 25(9):2363-70. DOI: 10.1634/stemcells.2006-0686. View

14.

Shibata K, Aoyama T, Shima Y, Fukiage K, Otsuka S, Furu M . Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion. Stem Cells. 2007; 25(9):2371-82. DOI: 10.1634/stemcells.2007-0225. View

15.

Caplan A . Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 2007; 213(2):341-7. DOI: 10.1002/jcp.21200. View

16.

Campisi J, dAdda di Fagagna F . Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007; 8(9):729-40. DOI: 10.1038/nrm2233. View

17.

Kastrinaki M, Sidiropoulos P, Roche S, Ringe J, Lehmann S, Kritikos H . Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis. Ann Rheum Dis. 2007; 67(6):741-9. DOI: 10.1136/ard.2007.076174. View

18.

Yue W, Liu W, Bi Y, He X, Sun W, Pang X . Mesenchymal stem cells differentiate into an endothelial phenotype, reduce neointimal formation, and enhance endothelial function in a rat vein grafting model. Stem Cells Dev. 2008; 17(4):785-93. DOI: 10.1089/scd.2007.0243. View

19.

Uccelli A, Moretta L, Pistoia V . Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2009; 8(9):726-36. DOI: 10.1038/nri2395. View

20.

Block G, Ohkouchi S, Fung F, Frenkel J, Gregory C, Pochampally R . Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem Cells. 2009; 27(3):670-681. PMC: 4742302. DOI: 10.1002/stem.20080742. View