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Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146(+) perivascular cells and fibroblasts
Open accessAbstract
Objective The relationship of multipotent mesenchymal stromal cells (MSC) with pericytes and fibroblasts has not been established thus far, although they share many markers of primitive marrow stromal cells and the osteogenic, adipogenic, and chondrogenic differentiation potentials.Materials and methods We compared MSCs from adult or fetal tissues, MSC differentiated in vitro, fibroblasts and cultures of retinal pericytes obtained either by separation with anti-CD146 or adhesion. The characterizations included morphological, immunophenotypic, gene-expression profile, and differentiation potential.Results Osteogenic, adipocytic, and chondrocytic differentiation was demonstrated for MSC, retinal perivascular cells, and fibroblasts. Cell morphology and the phenotypes defined by 22 markers were very similar. Analysis of the global gene expression obtained by serial analysis of gene expression for 17 libraries and by reverse transcription polymerase chain reaction of 39 selected genes from 31 different cell cultures, revealed similarities among MSC, retinal perivascular cells, and hepatic stellate cells. Despite this overall similarity, there was a heterogeneous expression of genes related to angiogenesis, in MSC derived from veins, artery, perivascular cells, and fibroblasts. Evaluation of typical pericyte and MSC transcripts, such as NG2, CD146, CD271, and CD140B on CD146 selected perivascular cells and MSC by real-time polymerase chain reaction confirm the relationship between these two cell types. Furthermore, the inverse correlation between fibroblast-specific protein-1 and CD146 transcripts observed on pericytes, MSC, and fibroblasts highlight their potential use as markers of this differentiation pathway.Conclusion Our results indicate that human MSC and pericytes are similar cells located in the wall of the vasculature, where they function as cell sources for repair and tissue maintenance, whereas fibroblasts are more differentiated cells with more restricted differentiation potential.
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ResultHuman Myocardial Pericytes: Multipotent Mesodermal Precursors Exhibiting Cardiac Specificity
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Progenitor Cells Identified by PDGFR-Alpha Expression in the Developing and Diseased Human Heart
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“CD146 is a membrane glycoprotein expressed on endothelial cells and may mark mesenchymal stromal cells with increased pluripotency [27-28].”
BackgroundMesenchymal stromal cells: misconceptions and evolving concepts
Phinney, D. G., & Sensebé, L. (2013) · Cytotherapy · doi:10.1016/j.jcyt.2012.11.005 · Cited by 125
“Nevertheless, closer scrutiny of these data reveal marked differences in expression levels of lineage-restricted messenger RNAs between pericytes and MSCs (10), and more rigorous in vivo assays demonstrate clear differences in function between cells from different tissues (11,12).”
BackgroundThe secretome of mesenchymal stem cells: Potential implications for neuroregeneration
Paul, G., & Anisimov, S. V. (2013) · Biochimie · doi:10.1016/j.biochi.2013.07.013 · Cited by 121
Pelekanos, R., Li, J., Gongora, M., Chandrakanthan, V., Scown, J., Suhaimi, N., Brooke, G. P., Christensen, M. E., Doan, T. B., Rice, A. M., et al. (2011) · Stem Cell Research · doi:10.1016/j.scr.2011.08.003 · Cited by 117
Mesenchymal Stem Cells and Pericytes: To What Extent Are They Related?
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Self-citationThe umbilical cord: a rich and ethical stem cell source to advance regenerative medicine
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“For example, CD146 was shown as marker of stem cells localized in the vascular wall [16], Nestin was found predominantly in multipotent cells from the central nervous system [17] and STRO-1 was expressed on mesenchymal stem cells in bone marrow [18].”
BackgroundIsolation and Characterization of Human Anterior Cruciate Ligament-Derived Vascular Stem Cells
Matsumoto, T., Ingham, S. M., Mifune, Y., Osawa, A., Logar, A., Ūsas, A., Kuroda, R., Kurosaka, M., Fu, F. H., & Huard, J. (2011) · Stem Cells and Development · doi:10.1089/scd.2010.0528 · Cited by 111
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“CD117 (c-kit), CD146 (the melanoma cell adhesion molecule described for pericytes, as well as for MSCs with colony-forming unit-fibroblast capacity) (17), and CD166 (ALCAM)] (20,45); ii) the epithelial marker CD326 (EpCAM); iii) the stage-specific embryonic antigen SSEA-4; iv) different types of integrins (CD49-a, CD4…”
BackgroundDPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis
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“The high proportion of CD146-positive cells may be correlated to increased blood vessel formation in inflamed pulp since CD146 is high in vascular endothelial cells, smooth muscle cells, and pericytes (Covas et al. 2008).”
BackgroundIsolation of human mesenchymal stromal cells is more efficient by red blood cell lysis
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“35 More importantly, PDLSCs exhibited the abilities to form bone/cementum-like mineralized tissue and ligament structures similar to Sharpey’s fibers with an associated vasculature.”
BackgroundReconstruction of human elastic cartilage by a CD44 + CD90 + stem cell in the ear perichondrium
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“It has been widely accepted that Mcam as a marker for identifying MSCs isolated from bone marrow, and its higher expression on the cell surface may be linked to greater multipotency and differentiation potential [Covas et al., 2008; Russell et al., 2010].”
BackgroundAAOS Research Symposium Updates and Consensus: Biologic Treatment of Orthopaedic Injuries
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“[4] Covas DT, Panepucci RA, Fontes AM, Silva WA Jr, Orellana MD, Freitas MC, et al.”
BackgroundPlacental Perivascular Cells for Human Muscle Regeneration
Park, T. S., Gavina, M., Chen, C.-W., Sun, B., Teng, P.-N., Huard, J., Deasy, B. M., Zimmerlin, L., & Péault, B. (2010) · Stem Cells and Development · doi:10.1089/scd.2010.0354 · Cited by 101
“Most cells expressing CD146 were also positive for PDGFR-b and NG2, further indicating their perivascular origin [23,26,27,32,33].”
Rossignoli, F., Caselli, A., Grisendi, G., Piccinno, M. S., Burns, J. S., Murgia, A., Veronesi, E., Loschi, P., Masini, C., Conte, P., et al. (2013) · BioMed Research International · doi:10.1155/2013/901821 · Cited by 97
Vascular Wall as a Reservoir for Different Types of Stem and Progenitor Cells
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“Although several studies have demonstrated similarities between peri-ECs of capillaries and MSCs (23, 88, 94, 96, 119), neither stringent cellular characterization, for example, in situ double immunostainings using different markers, nor exact cell-sorting analyses were performed yet to exactly…”
Cell Interaction with Nanopatterned Surface of Implants
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Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue
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One-step derivation of cardiomyocytes and mesenchymal stem cells from human pluripotent stem cells.
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“There is strong evidence that bone marrow-derived mesenchymal stem cells (MSCs) have the potential to generate a vast array of growth factors, chemokines, and extracellular matrix molecules,(12-14) and closely share cellular and molecular properties with pericytes.(15,16) The purpose of the current clinical phase 1 in…”
BackgroundPerivascular cells as mesenchymal stem cells
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“2 Mesenchymal stem cells (MSCs) from other tissues Based on the typical mesenchymal stem cell properties of cells isolated from bone marrow such as colony-forming, self-renewal and mesenchymal lineage differentiation potentials, an increasing number of cell populations with MSClike characteristics have been reported f…”
BackgroundCharacterization of bone marrow derived mesenchymal stem cells in suspension
Akiyama, K., You, Y., Yamaza, T., Chen, C., Tang, L. V., Jin, Y. J., Chen, X., Gronthos, S., & Shi, S. (2012) · Stem Cell Research & Therapy · doi:10.1186/scrt131 · Cited by 97
“It is generally believed that BMMSCs are negative for hematopoietic cell markers such as CD14 and CD34 [5-13].”
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“demonstrated a similar gene expression profile of retinal PCs compared to MSCs from 12 different fetal and adult tissues [13], highlighting the close relationship of both cell populations.”
BackgroundResultInfluential
Metadata
- Authors
- Covas, D. T., Panepucci, R. A., Fontes, A. M., Silva, W. A., Orellana, M. D., Freitas, M. C. C., Neder, L., Santos, A. R. D., Peres, L. C., Jamur, M. C., & Zago, M. A.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Covas, Dimas T.
- ORCID
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 36
- Issue
- 5
- Pages
- 642-654
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W1979782761
- Cited by
- 610
- References
- 93
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 15 · 2023: 14 · 2022: 19 · 2021: 25 · 2020: 31 · 2019: 31 · 2018: 32 · 2017: 32 · 2016: 48 · 2015: 58 · 2014: 49 · 2013: 60 · 2012: 63
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Funders
- Scheme for Promotion of Academic and Research Collaboration
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- mesenchymal stem cells, pericytes, fibroblasts, CD146, hepatic stellate cells, gene expression profiling, osteogenic differentiation, adipogenesis, chondrogenic differentiation, angiogenesis, S100A4, NG2, p75 neurotrophin receptor, PDGFRβ, vascular wall cells, tissue repair
- MeSH terms
- Cell Differentiation, Cell Separation, Cells, Cultured, Fibroblasts, Flow Cytometry, Humans, Transcription, Genetic, Umbilical Cord, Cluster Analysis, Immunophenotyping, Reverse Transcriptase Polymerase Chain Reaction, Pericytes, Gene Expression Profiling, CD146 Antigen, Mesenchymal Stem Cells
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