The Profile of Gene Expression of Human Marrow Mesenchymal Stem Cells

Silva, Wilson A.; Covas, Dimas Tadeu; Panepucci, Rodrigo Alexandre; Proto‐Siqueira, Rodrigo; Siufi, J. L. C.; Zanette, Dalila Lucíola; Santos, Anemari Ramos Dinarte dos; Zago, Marco Antônio

doi:10.1634/stemcells.21-6-661

Cited by 274 publications

(202 citation statements)

References 35 publications

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“…Consistent with our results, MMP-2 mRNA expression has been previously detected in hMSCs isolated from bone marrow and umbilical cord blood. 32,48,49 Others had shown a cytoplasmatic localization of MMP-2 in hMSCs and its regulation by cancer-associated genes. 50 Although the investigators suspected the enzyme to be implicated in hMSC migration, they did not provide direct evidence for this assumption.…”

Section: Discussionmentioning

confidence: 99%

MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines

Ries

Egea

Karow

et al. 2007

Blood

477

384

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IntroductionHuman mesenchymal stem cells (hMSCs) from bone marrow are characterized by their ability of self-renewal paired with the capacity to differentiate into diverse mesodermal cell types such as osteoblasts, chondrocytes, and adipocytes. 1,2 Moreover, hMSCs were shown to give rise to cells beyond the germ layers with visceral mesoderm, neuroectoderm, or endoderm characteristics. [2][3][4] Additional functions have been reported for hMSCs in providing cytokine and growth factor support for the expansion of hematopoetic 5 and embryonic stem cells, 6 or by playing an immunomodulatory role. 7 One of the most remarkable but least understood findings is the ability of hMSCs to migrate from bone marrow or peripheral blood into damaged tissues. Transplantation experiments in animals and patients demonstrated that mesenchymal stem cells migrate to sites of injury, where they enhance wound healing, 8 support tissue regeneration following myocardial infarction, 9 home to and promote the restoration of bone marrow microenvironment after damage by myeloablative chemotherapy, 10 or help to overcome the molecular defect in children with osteogenesis imperfecta. 11 Another interesting observation is that systemically delivered hMSCs are mobilized to and integrate into tumor tissue. 12 Taken together, these exciting features have rendered hMSCs a promising tool for tissue engineering 13 as well as multiple cell and gene therapy strategies. [14][15][16] Detailed studies have demonstrated that homing of hematopoetic stem cells from blood into bone marrow or their mobilization from bone marrow into blood and tissues is mainly controlled by cytokines/chemokines, adhesion molecules, and proteolytic enzymes. [17][18][19] However, little is known about the molecular mechanisms regulating cell movement and relocalization in hMSCs.A key requirement for cells to reach distant target sites is the ability to traverse the protein fibers of the extracellular matrix (ECM) which is present between cells of all tissue types. 20 Basement membranes represent a specialized form of the ECM that separate epithelium or endothelium from stroma by a dense layer of ECM. To overcome these matrix barriers, migrating cells require specific proteolytic enzymes. Besides some serine-and cysteineproteinases, in particular the matrix metalloproteinases (MMPs) consisting of more than 24 zinc-dependent endopeptidases, are capable of degrading ECM components. Consequently, MMPs are found to be involved in various physiologic and pathologic processes. 21 The 2 gelatinases, MMP-2 and MMP-9, preferentially cleave denatured collagens (gelatin), laminin, and collagen type IV as the major constituent of basement membranes. 20,21 Biosynthesis and activity of the gelatinases are associated with the invasive capacity of various cell types such as leukocytes, endothelial cells, and metastasizing tumor cells. 22-24 MMP-2 and MMP-9 are secreted from the cells as latent zymogens which are rapidly complexed by their specific endogenous inhibitors, the tissue inhibitor of ...

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Section: Discussionmentioning

confidence: 99%

MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines

Ries

Egea

Karow

et al. 2007

Blood

477

384

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the predominant source of IL-17A (henceforth referred to as IL-17) remains the CD4 + memory T cell population [4,33]. The broad cell and tissue distribution of receptors for IL-17 (of which five have been described, namely IL-17R (the dominant receptor for IL-17A), IL-17RB, IL-17RC, IL-17RD and IL-17RE) in both humans and mice [27,29,30,[36][37][38] and the diversity of expression through alternate splicing (reviewed in Moseley et al 2003 [39]) argues for a pleiotropic spectrum of biological activity that may extend beyond the purely immunological, with the potential to act on many different cell types. Indeed, experiments in animals suggest that, unlike other cytokines, very little redundancy exists in the IL-17 network as IL-17R-deficient mice are very susceptible to lethal bacterial infections [40] and have inhibited T cell responses [41].…”

Section: Il-17mentioning

confidence: 99%

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali

Lombardi

Lechler

et al. 2007

Clinical and Experimental Immunology

649

470

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“…MSCs express several cellsurface antigens such as CD73, CD90, CD105, CD146, and even the recently described CD200 (13), as well as various integrins and adhesion molecules. Because MSCs are a nonhematopoietic cell line, they do not express hematopoietic markers such as CD34, CD14, or CD45 (14). Adult human MSCs express intermediate levels of major histocompatibility complex class I molecules on their cell surface but not major histocompatibility complex class II molecules, a property that allows them to be transplanted across major histocompatibility complex barriers.…”

Section: Sources Of Mscsmentioning

confidence: 99%

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

2012

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The Profile of Gene Expression of Human Marrow Mesenchymal Stem Cells

Abstract: ABSTRACT

Cited by 274 publications

References 35 publications

MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines

MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

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