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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Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766 · see citing works
Mesenchymal stem cells
Caplan, A. I. (1991) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100090504 · Cited by 6,563 · see citing works
Self-citation
Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues
Prockop, D. J. (1997) · Science · doi:10.1126/science.276.5309.71 · Cited by 4,629 · see citing works
Human mesenchymal stem cells modulate allogeneic immune cell responses
Aggarwal, S., & Pittenger, M. F. (2005) · Blood · doi:10.1182/blood-2004-04-1559 · Cited by 4,511 · see citing works
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991 · see citing works
Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli
Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., & Gianni, A. M. (2002) · Blood · doi:10.1182/blood.v99.10.3838 · Cited by 3,226 · see citing works
Mesenchymal stem cells as trophic mediators
Caplan, A. I., & Dennis, J. E. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20886 · Cited by 2,992 · see citing works
Self-citation
Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells
Le Blanc, K., Rasmusson, I., Sundberg, B., Götherström, C., Hassan, M., Uzunel, M., & Ringdén, O. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16104-7 · Cited by 2,734 · see citing works
Mesenchymal stem cells reside in virtually all post-natal organs and tissues
Meirelles, L. D. S., Chagastelles, P. C., & Nardi, N. B. (2006) · Journal of Cell Science · doi:10.1242/jcs.02932 · Cited by 2,472 · see citing works
Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches
Sugiyama, T., Kohara, H., Noda, M., & Nagasawa, T. (2006) · Immunity · doi:10.1016/j.immuni.2006.10.016 · Cited by 2,419 · see citing works
Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production
Németh, K., Leelahavanichkul, A., Yuen, P. S. T., Mayer, B., Parmelee, A., Doi, K., Robey, P. G., Leelahavanichkul, K., Koller, B. H., Brown, J. M., et al. (2009) · Nature Medicine · doi:10.1038/nm.1905 · Cited by 2,364 · see citing works
Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells
Rehman, J., Traktuev, D., Li, J., Merfeld-Clauss, S., Temm-Grove, C. J., Bovenkerk, J. E., Pell, C. L., Johnstone, B. H., Considine, R. V., & March, K. L. (2004) · Circulation · doi:10.1161/01.cir.0000121425.42966.f1 · Cited by 2,269 · see citing works
Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment
Sacchetti, B., Funari, A., Michienzi, S., Di Cesare, S., Piersanti, S., Saggio, I., Tagliafico, E., Ferrari, S., Robey, P. G., Riminucci, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.025 · Cited by 2,226 · see citing works
Conditions controlling the proliferation of haemopoietic stem cells in vitro
Dexter, T. M., Allen, T., & Lajtha, L. G. (1977) · Journal of Cellular Physiology · doi:10.1002/jcp.1040910303 · Cited by 2,120 · see citing works
Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement
Horwitz, E. M., Blanc, K. L., Dominici, M., Mueller, I., Slaper‐Cortenbach, I., Marini, F. C., Deans, R. J., Krause, D. S., & Keating, A. (2005) · Cytotherapy · doi:10.1080/14653240500319234 · Cited by 2,074 · see citing works
Chemokines
Rollins, B. J. (1997) · Blood · doi:10.1182/blood.v90.3.909 · Cited by 1,983 · see citing works
Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications
Bianco, P., Riminucci, M., Gronthos, S., & Robey, P. G. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-180 · Cited by 1,944 · see citing works
Human mesenchymal stem cells modulate B-cell functions
Corcione, A., Benvenuto, F., Ferretti, E., Giunti, D., Cappiello, V., Cazzanti, F., Risso, M., Gualandi, F., Mancardi, G. L., Pistoia, V., et al. (2006) · Blood · doi:10.1182/blood-2005-07-2657 · Cited by 1,767 · see citing works
Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradation
Meisel, R., Zibert, A., Laryea, M. D., Göbel, U., Däubener, W., & Dilloo, D. (2004) · Blood · doi:10.1182/blood-2003-11-3909 · Cited by 1,638 · see citing works
Mesenchymal Stem Cells: Revisiting History, Concepts, and Assays
Bianco, P., Robey, P. G., & Simmons, P. J. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.03.002 · Cited by 1,625 · see citing works
Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide
Krampera, M., Glennie, S. J., Dyson, J., Scott, D. M., Laylor, R. M., Simpson, E., & Dazzi, F. (2003) · Blood · doi:10.1182/blood-2002-07-2104 · Cited by 1,597 · see citing works
Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp
Shi, S., & Gronthos, S. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.4.696 · Cited by 1,479 · see citing works
Mesenchymal Stem Cell Homing: The Devil Is in the Details
Karp, J. M., & Leng Teo, G. S. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.02.001 · Cited by 1,445 · see citing works
Mesenchymal Stem Cells Inhibit and Stimulate Mixed Lymphocyte Cultures and Mitogenic Responses Independently of the Major Histocompatibility Complex
Blanc, K. L., Tammik, L., Sundberg, B., Haynesworth, S. E., & Ringdén, O. T. H. (2003) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2003.01176.x · Cited by 1,367 · see citing works
Local Delivery of Marrow-Derived Stromal Cells Augments Collateral Perfusion Through Paracrine Mechanisms
Kinnaird, T. D., Stabile, E., Burnett, M. S., Shou, M., Lee, C. W., Barr, S., Fuchs, S., & Epstein, S. E. (2004) · Circulation · doi:10.1161/01.cir.0000124062.31102.57 · Cited by 1,304 · see citing works
Mesenchymal stem cells: building blocks for molecular medicine in the 21st century
Caplan, A. I., & Bruder, S. P. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02016-0 · Cited by 1,138 · see citing works
Self-citation
White Fat Progenitor Cells Reside in the Adipose Vasculature
Tang, W., Zeve, D., Suh, J. M., Bosnakovski, D., Kyba, M., Hammer, R. E., Tallquist, M. D., & Graff, J. M. (2008) · Science · doi:10.1126/science.1156232 · Cited by 1,113 · see citing works
In Search of the In Vivo Identity of Mesenchymal Stem Cells
da Silva Meirelles, L., Caplan, A. I., & Nardi, N. B. (2008) · Stem Cells · doi:10.1634/stemcells.2007-1122 · Cited by 1,077 · see citing works
Self-citation
Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation
Spaggiari, G. M., Capobianco, A., Becchetti, S., Mingari, M. C., & Moretta, L. (2005) · Blood · doi:10.1182/blood-2005-07-2775 · Cited by 1,057 · see citing works
Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model
Muraglia, A., Cancedda, R., & Quarto, R. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.7.1161 · Cited by 1,025 · see citing works
Interactions Between Human Mesenchymal Stem Cells and Natural Killer Cells
Sotiropoulou, P. A., Perez, S. A., Gritzapis, A. D., Baxevanis, C. N., & Papamichail, M. (2006) · Stem Cells · doi:10.1634/stemcells.2004-0359 · Cited by 956 · see citing works
Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells
Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K., & Ozawa, K. (2006) · Blood · doi:10.1182/blood-2006-02-002246 · Cited by 952 · see citing works
The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities
Ponte, A. L., Marais, E., Gallay, N., Langonné, A., Delorme, B., Hérault, O., Charbord, P., & Domenech, J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0054 · Cited by 947 · see citing works
A Neurovascular Niche for Neurogenesis after Stroke
Ohab, J. J., Fleming, S., Blesch, A., & Carmichael, S. T. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4323-06.2006 · Cited by 878 · see citing works
Bone Marrow–Derived Mesenchymal Stem Cells in Repair of the Injured Lung
Rojas, M., Xu, J., Woods, C. R., Mora, A. L., Spears, W., Roman, J., & Brigham, K. L. (2005) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2004-0330oc · Cited by 849 · see citing works
A Population of Multipotent CD34-Positive Adipose Stromal Cells Share Pericyte and Mesenchymal Surface Markers, Reside in a Periendothelial Location, and Stabilize Endothelial Networks
Traktuev, D. O., Merfeld‐Clauss, S., Li, J., Kolonin, M. G., Arap, W., Pasqualini, R., Johnstone, B. H., & March, K. L. (2007) · Circulation Research · doi:10.1161/circresaha.107.159475 · Cited by 839 · see citing works
Marrow stromal stem cells
Owen, M. E. (1988) · Journal of Cell Science · doi:10.1242/jcs.1988.supplement_10.5 · Cited by 829 · see citing works
Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates
Yoshimura, K., Shigeura, T., Matsumoto, D., Sato, T., Takaki, Y., Aiba‐Kojima, E., D, K. S. M., Inoue, K., Nagase, T., Koshima, I., et al. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20636 · Cited by 804 · see citing works
Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: Effects of dexamethasone and IL-1α
Haynesworth, S. E., Baber, M. A., & Caplan, A. I. (1996) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199603)166:3 · Cited by 658 · see citing works
Self-citation
Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury
Togel, F. E., Weiss, K., Yang, Y., Hu, Z., Zhang, P., & Westenfelder, C. S. (2007) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00339.2006 · Cited by 642 · see citing works
Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146(+) perivascular cells and fibroblasts
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., et al. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2007.12.015 · Cited by 610 · cited 1× · see citing works
“adipogenic, osteogenic and chondrogenic lineages ([25]; reviewed in [38]).”
BackgroundSelf-citation
Interferon-γ does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells
Ryan, J. M., Barry, F., Murphy, M. J., & Mahon, B. P. (2007) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2007.03422.x · Cited by 596 · see citing works
Vascular Pericytes Express Osteogenic Potential In Vitro and In Vivo
Doherty, M. J., Ashton, B. A., Walsh, S., Beresford, J. N., Grant, M. E., & Canfield, A. E. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.828 · Cited by 566 · see citing works
Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells
Rüster, B., Göttig, S., Ludwig, R. J., Bistrian, R., Müller, S., Seifried, E., Gille, J., & Henschler, R. (2006) · Blood · doi:10.1182/blood-2006-05-025098 · Cited by 562 · see citing works
Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure
Parekkadan, B., van Poll, D., Suganuma, K., Carter, E. A., Francois Berthiaume, B., Tilles, A. W., & Yarmush, M. L. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000941 · Cited by 510 · see citing works
Chondrogenic and Adipogenic Potential of Microvascular Pericytes
Farrington, C., Crofts, N. J., Doherty, M. J., Ashton, B. A., Griffin-Jones, C., & Canfield, A. E. (2004) · Circulation · doi:10.1161/01.cir.0000144457.55518.e5 · Cited by 470 · see citing works
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
Hung, S.-C., Pochampally, R. R., Chen, S.-C., Hsu, S.-C., & Prockop, D. J. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0686 · Cited by 457 · see citing works
Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ
Chan, J. L., Tang, K. C., Patel, A. P., Bonilla, L., Pierobon, N., Ponzio, N. M., & Rameshwar, P. (2006) · Blood · doi:10.1182/blood-2006-01-0057 · Cited by 419 · see citing works
Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury
Sanchez, M. B. H., Bussolati, B., Bruno, S., Morando, L., Mauriello-Romanazzi, G., Sanavio, F., Stamenkovic, I., Biancone, L., & Camussi, G. (2007) · Kidney International · doi:10.1038/sj.ki.5002334 · Cited by 378 · see citing works
Immunosuppressive Effects of Mesenchymal Stem Cells: Involvement of HLA-G
Nasef, A., Mathieu, N., Chapel, A., Frick, J., François, S., Mazurier, C., Boutarfa, A., Bouchet, S., Gorin, N.-C., Thierry, D., et al. (2007) · Transplantation · doi:10.1097/01.tp.0000267918.07906.08 · Cited by 350 · see citing works
The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair
Arthur, A., Zannettino, A. C. W., & Gronthos, S. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21592 · Cited by 332 · see citing works
Comparison of Gene Expression of Umbilical Cord Vein and Bone Marrow–Derived Mesenchymal Stem Cells
Panepucci, R. A., Siufi, J. L. C., Silva, W. A., Proto‐Siquiera, R., Neder, L., Orellana, M. D., Rocha, V., Covas, D. T., & Zago, M. A. (2004) · Stem Cells · doi:10.1634/stemcells.2004-0024 · Cited by 330 · see citing works
Self-citation
Mesenchymal cells recruit and regulate T regulatory cells
Ianni, M. D., Papa, B. D., Ioanni, M. D., Moretti, L., Bonifacio, E., Cecchini, D., Sportoletti, P., Falzetti, F., & Tabilio, A. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2007.11.007 · Cited by 315 · see citing works
The Profile of Gene Expression of Human Marrow Mesenchymal Stem Cells
Silva, W. A., Covas, D. T., Panepucci, R. A., Proto‐Siqueira, R., Siufi, J. L. C., Zanette, D. L., dos Santos, A. R. D., & Zago, M. A. (2003) · Stem Cells · doi:10.1634/stemcells.21-6-661 · Cited by 313 · see citing works
Self-citation
The Pericyte as a Possible Osteoblast Progenitor Cell
Brighton, C. T., Lorich, D. G., Kupcha, R., REILLY, T. M., JONES, A. R., & WOODBURY, R. A. (1992) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-199202000-00043 · Cited by 299 · see citing works
Human and animal mesenchymal progenitor cells from bone marrow: Identification of serum for optimal selection and proliferation
Lennon, D. P., Haynesworth, S. E., Bruder, S. P., Jaiswal, N., & Caplan, A. I. (1996) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02724045 · Cited by 284 · see citing works
Self-citation
Bone Marrow-Derived Mesenchymal Stem Cells Induce Both Polyclonal Expansion and Differentiation of B Cells Isolated from Healthy Donors and Systemic Lupus Erythematosus Patients
Traggiai, E., Volpi, S., Schena, F., Gattorno, M., Ferlito, F., Moretta, L., & Martini, A. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0528 · Cited by 282 · see citing works
Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies
Iyer, S. S., & Rojas, M. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.5.569 · Cited by 269 · see citing works
Immunophenotypic analysis of human articular chondrocytes: Changes in surface markers associated with cell expansion in monolayer culture
Diaz‐Romero, J., Gaillard, J. P., Grogan, S. P., Nešić, D., Trüb, T., & Mainil‐Varlet, P. (2004) · Journal of Cellular Physiology · doi:10.1002/jcp.20164 · Cited by 267 · see citing works
Identification of Label-Retaining Cells in Mouse Endometrium
Chan, R., & Gargett, C. E. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0411 · Cited by 265 · see citing works
Pericytes as a Supplementary Source of Osteoblasts in Periosteal Osteogenesis
Díaz‐Flores, L., Gutiérrez, R., López‐Alonso, A., et al. (1992) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-199202000-00042 · Cited by 258 · see citing works
Stable Expression of Angiopoietin-1 and Other Markers by Cultured Pericytes: Phenotypic Similarities to a Subpopulation of Cells in Maturing Vessels During Later Stages of Angiogenesis In Vivo
Sundberg, C., Kowanetz, M., Brown, L. F., Detmar, M. J., & Dvorak, H. F. (2002) · Laboratory Investigation · doi:10.1038/labinvest.3780433 · Cited by 253 · see citing works
Progenitor cells of the testosterone-producing Leydig cells revealed
Davidoff, M. S., Middendorff, R., Enikolopov, G., Riethmacher, D., Holstein, A. F., & Müller, D. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200409107 · Cited by 252 · see citing works
Multipotent Stromal Cells Are Activated to Reduce Apoptosis in Part by Upregulation and Secretion of Stanniocalcin-1
Block, G. J., Ohkouchi, S., Fung, F. W., Frenkel, J., Gregory, C. A., Pochampally, R. R., DiMattia, G. E., Sullivan, D. E., & Prockop, D. J. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0742 · Cited by 238 · see citing works
Identification of IL-10 and TGF-β Transcripts Involved in the Inhibition of T-Lymphocyte Proliferation During Cell Contact With Human Mesenchymal Stem Cells
Nasef, A., Chapel, A., Mazurier, C., Bouchet, S., Lopez, M., Mathieu, N., Sensebé, L., Zhang, Y., Gorin, N. C., Thierry, D., et al. (2006) · Gene Expression · doi:10.3727/000000006780666957 · Cited by 227 · see citing works
Mesenchymal stromal cell–derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction
Rafei, M., Hsieh, J., Fortier, S., Li, M., Yuan, S., Birman, E., Forner, K., Boivin, M., Doody, K. M., Tremblay, M. L., et al. (2008) · Blood · doi:10.1182/blood-2008-07-166892 · Cited by 223 · see citing works
Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms
Segers, V. F. M., Riet, I. V., Andries, L. J., Lemmens, K., Demolder, M. J., Becker, A. D., Kockx, M. M., & Keulenaer, G. W. D. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00523.2005 · Cited by 204 · see citing works
Progenitor cell populations in the periodontal ligament of mice
McCulloch, C. A. (1985) · The Anatomical Record · doi:10.1002/ar.1092110305 · Cited by 189 · see citing works
Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression
Nasef, A., Mazurier, C., Bouchet, S., François, S., Chapel, A., Thierry, D., Gorin, N. C., & Fouillard, L. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2008.06.002 · Cited by 177 · see citing works
Methodology, biology and clinical applications of mesenchymal stem cells
Meirelles, L. D. S. (2009) · Frontiers in bioscience · doi:10.2741/3528 · Cited by 169 · see citing works
IFATS Collection: Fibroblast Growth Factor-2-Induced Hepatocyte Growth Factor Secretion by Adipose-Derived Stromal Cells Inhibits Postinjury Fibrogenesis Through a c-Jun N-Terminal Kinase-Dependent Mechanism
Suga, H., Eto, H., Shigeura, T., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0261 · Cited by 163 · see citing works
Influence of Adult Mesenchymal Stem Cells on In Vitro Vascular Formation
Sorrell, J. M., Baber, M. A., & Caplan, A. I. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0254 · Cited by 157 · see citing works
Self-citation
Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure
Li, L., Zhang, S., Zhang, Y., Yu, B., Xu, Y., & Guan, Z. (2008) · Molecular Biology Reports · doi:10.1007/s11033-008-9235-2 · Cited by 153 · see citing works
Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes
Rasmusson, I., Uhlin, M., Blanc, K. L., & Levitsky, V. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0307140 · Cited by 151 · see citing works
Building a consensus regarding the nature and origin of mesenchymal stem cells
Phinney, D. G. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10084 · Cited by 136 · see citing works
Isolation and Characterization of Resident Mesenchymal Stem Cells in Human Glomeruli
Bruno, S., Bussolati, B., Grange, C., Collino, F., di Cantogno, L. V., Sanchez, M. B. H., Biancone, L., Tetta, C., Segoloni, G., & Camussi, G. (2009) · Stem Cells and Development · doi:10.1089/scd.2008.0320 · Cited by 130 · see citing works
MSC Frequency Correlates with Blood Vessel Density in Equine Adipose Tissue
Meirelles, L. D. S., Sand, T. T., Harman, R. J., Lennon, D. P., & Caplan, A. I. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0103 · Cited by 121 · see citing works
Self-citation
Early Histologic and Ultrastructural Changes in Microvessels of Periosteal Callus
Brighton, C. T., & Hunt, R. M. (1997) · Journal of Orthopaedic Trauma · doi:10.1097/00005131-199705000-00002 · Cited by 111 · see citing works
The strict regulation of lymphocyte migration to splenic white pulp does not involve common homing receptors
Nolte, M. A., Hamann, A., Kraal, G., et al. (2002) · Immunology · doi:10.1046/j.1365-2567.2002.01443.x · Cited by 110 · see citing works
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Mesenchymal stem cells can be obtained from the human saphena vein
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Self-citation
Dexamethasone Inhibits High Glucose–, TNF-α–, and IL-1β–Induced Secretion of Inflammatory and Angiogenic Mediators from Retinal Microvascular Pericytes
Nehmé, A., & Edelman, J. L. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0273 · Cited by 88 · see citing works
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Sanz, L., Santos-Valle, P., Alonso-Camino, V., Salas, C., Serrano, A., Vicario, J. L., Cuesta, Á. M., Compte, M., Sánchez‐Martín, D., & Álvarez‐Vallina, L. (2008) · Microvascular Research · doi:10.1016/j.mvr.2007.11.007 · Cited by 82 · see citing works
A functional role for soluble HLA-G antigens in immune modulation mediated by mesenchymal stromal cells
Rizzo, R., Campioni, D., Stignani, M., et al. (2008) · Cytotherapy · doi:10.1080/14653240802105299 · Cited by 77 · see citing works
Inducible perivascular cells contribute to the neochondrogenesis in grafted perichondrium
Díaz‐Flores, L., Gutiérrez, R., González, P., & Varela, H. (1991) · The Anatomical Record · doi:10.1002/ar.1092290102 · Cited by 66 · see citing works
Hypoxic osteocytes recruit human MSCs through an OPN/CD44-mediated pathway
Raheja, L. F., Genetos, D. C., & Yellowley, C. E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.12.076 · Cited by 66 · see citing works
Response of Pericytes to Thermal Lesion in the Inguinal Fat Pad of 10-Day-Old Rats
Richardson, R. L., Hausman, G., & Campion, D. R. (1982) · Cells Tissues Organs · doi:10.1159/000145577 · Cited by 59 · see citing works
Histochemical and ultrastructural characteristics of a cell line from human bone-marrow stroma
Lanotte, M., Allen, T., & Dexter, T. M. (1981) · Journal of Cell Science · doi:10.1242/jcs.50.1.281 · Cited by 49 · see citing works
Postgastrulation effects of fibroblast growth factor on Xenopus development
Lombardo, A., & Slack, J. M. W. (1998) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199805)212:1 · Cited by 48 · see citing works
Metallic wires with an adherent lubricious and blood-compatible polymeric coating and their use in the manufacture of novel slippery-when-wet guidewires: Possible applications related to controlled local drug delivery
Hanssen, H. H. L., Wetzels, G. M. R., Benzina, A., van der Veen, F. H., Lindhout, T., & Koole, L. H. (1999) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(1999)48:6 · Cited by 32 · see citing works
Differential expression of stromal cell-derived factor 1 in human brain microvascular endothelial cells and pericytes involves histone modifications
Seo, J., Kim, Y., & Jo, I. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.049 · Cited by 24 · see citing works
Untitled work
Collins (1998) · doi:10.1002/(sici)1097-4652(199807)176:1

Flagged first, then by citations

Research works printed but not linked: 4

[3]3. Ohgushi H, Caplan AI. Stem cell technology and bioceramics: from cell to gene engineering. J Biomed Mater Res 1999;48(6):913-27.
[22]22. Fleming Jr JE, Haynesworth SE, Cassiede P, Baber MA, Caplan AI. Monoclonal antibody against adult marrow-derived mesenchymal stem cells recognizes developing vasculature in embryonic human skin. Dev Dyn 1998;212(1):119- 32.
[84]84. Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998;176(1):57-66.
[93]93. Rollins BJ. Chemokines. Blood 1997;90(3):909-28.

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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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