Mechanisms involved in the therapeutic properties of mesenchymal stem cells

da Silva Meirelles, Lindolfo; Fontes, Aparecida Maria; Covas, Dimas Tadeu; Caplan, Arnold I.

doi:10.1016/j.cytogfr.2009.10.002

Cited by 1,436Mesenchymal stem cell researchPeriodontal Regeneration and TreatmentsHematopoietic Stem Cell Transplantation

Mechanisms involved in the therapeutic properties of mesenchymal stem cells

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da Silva Meirelles, Lindolfo, Fontes, Aparecida Maria, Covas, Dimas Tadeu, Caplan, Arnold I.·2009·Cytokine & Growth Factor Reviews

DOI 10.1016/j.cytogfr.2009.10.002

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Abstract

Mesenchymal stem cells (MSCs) have been described as being able to give rise to several quite different mesenchymal cell phenotypes. However, the ability to differentiate is not the only characteristic that makes these cells attractive for therapeutic purposes. The secretion of a broad range of bioactive molecules by MSCs, such as growth factors, cytokines and chemokines, constitutes their most biologically significant role under injury conditions. Understanding this intricate secretory activity as well as the properties of MSCs in vivo is central to harnessing their clinical potential. Herein, we identify some of the molecules involved in the paracrine effects of MSCs with a perspective that these cells intrinsically belong to a perivascular niche in vivo, and discuss how this knowledge could be advantageously used in clinical applications.

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IL-6 is an MSC-secreted inflammatory cytokine with pro-survival, pro-growth and pro-angiogenic activities, and it has been implicated in tumor progression in various cancers including breast cancer.
“IL-6 is an MSC-secreted inflammatory cytokine displaying pro-survival, pro-growth and pro-angiogenic activities [11], which has been implicated in tumor progression of various cancers including breast cancer [113, 114].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [11]
Section 3.2.4 says cultured MSCs secrete IL-6 as part of their support for hematopoiesis, and Section 3.2.5 and Table 1 classify it among angiogenic factors. Section 3.2.5 describes anti-apoptotic effects of MSC-conditioned medium containing IL-6, but does not establish IL-6 itself as the cause or clearly establish its individual pro-growth activity. The tumor-progression clause is cited to [113, 114], not to this source, and is not part of this verdict. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Most MSC-secreted factors form a common core regardless of tissue origin, including overlapping anti-apoptotic, immunomodulatory, anti-scarring, supportive, angiogenic and chemoattractant factors such as IL6, CCL2, PAI-1, TGFβ1, CD106 and VEGF.
“The bulk of MSC-secreted factors comprises a common core, independently of their tissue of origin, including an overlapping set of anti-apoptotic, immunomodulatory, anti-scarring, supportive, angiogenic and chemoattractant factors such as interleukin-6 (IL6), chemokine C-C motif ligand 2 (CCL2), PAI-1, transforming growth factor-beta1 (TGFβ1), CD106 and vascular endothelial growth factor (VEGF) [”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [11]
Table 1 (section 4, page unavailable) lists the six functional categories and includes IL-6, CCL2, TGF-β and VEGF among factors associated with cultured MSCs. It does not establish that most secreted factors form a common core independent of tissue origin, and it does not list PAI-1 or CD106 as secreted factors. (LLM, conf=0.88)
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Authors: da Silva Meirelles, L., Fontes, A. M., Covas, D. T., & Caplan, A. I.
Affiliations: Universidade de São Paulo (BR)
Case Western Reserve University (US)
Corresponding author: Caplan, Arnold I.
ORCID: Fontes, Aparecida Maria
Covas, Dimas Tadeu
Caplan, Arnold I.
Venue: Cytokine & Growth Factor Reviews
Publisher: Elsevier BV
Published: 2009-10
Volume: 20
Issue: 5-6
Pages: 419-427
ISSN: 1359-6101 (ISSN-L)
DOI: 10.1016/j.cytogfr.2009.10.002
OpenAlex: W2071904806
Cited by: 1,436
References: 93
Citations by year: 2026: 13 · 2025: 33 · 2024: 56 · 2023: 67 · 2022: 102 · 2021: 114 · 2020: 147 · 2019: 126 · 2018: 112 · 2017: 96 · 2016: 94 · 2015: 110 · 2014: 114 · 2013: 85 · 2012: 76
FWCI: 6.59
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 413 d)
Locations: Cytokine & Growth Factor Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Financiadora de Estudos e Projetos
National Institutes of Health
Topics: Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords: mesenchymal stem cells, paracrine signaling, secretome, growth factors, cytokines, chemokines, perivascular niche, tissue damage, stem cell therapy, cell differentiation
MeSH terms: Animals, Cell Differentiation, Cell Movement, Cicatrix, Humans, Models, Biological, Apoptosis, Paracrine Communication, Angiogenesis Inducing Agents, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Mesenchymal Stem Cells

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Mechanisms involved in the therapeutic properties of mesenchymal stem cells

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