Human Marrow-Derived Mesenchymal Stem Cells (MSCs) Express Hematopoietic Cytokines and Support Long-Term Hematopoiesis When Differentiated Toward Stromal and Osteogenic Lineages

Majumdar, Manas K.; Thiede, Mark A.; Haynesworth, Stephen E.; Bruder, Scott P.; Gerson, Stanton L.

doi:10.1089/152581600750062264

Cited by 401 publications

(286 citation statements)

References 13 publications

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“…This finding was in concurrence with previous studies reporting that MSCs, derived from patients who had undertaken chemotherapeutic treatments for various different malignancies, produce normal levels of hemopoietic support in vitro [6,8,41]. The role of MSC damage in engraftment kinetics in vivo is unknown; however, it is known that MSCs can produce a number of early-acting cytokines that maintain HSC in quiescence or promote their self-renewal and also a variety of interleukins and cytokines which act on more mature hematopoietic progenitors [33,34].…”

Section: Discussionmentioning

confidence: 98%

“…CD44 is an adhesion molecule that plays a critical role in normal hematopoiesis [31,32], and it is the stromal microenvironment consisting of stromal cells and extracellular matrix that is thought to regulate and support the future fate of stem cells and committed progenitors along specific lineages [33][34][35]. The role and function of CD44 have been extensively studied on the surface of hemopoietic cells, however, much less so when concerning its presence on MSCs.…”

Section: Discussionmentioning

confidence: 99%

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Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

et al. 2010

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Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDCinduced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

et al. 2010

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“…Under this special ocular microenvironment, these stem cells can be fully activated by expressing AC133, CD34, c-Kit, and STRO-1 receptor, and they produce certain cytokines and growth factors such as IL-6, IL-11, SCF, and GM-CSF. 31 These factors may have both effect on themselves and limbal basal stem cells, resulting in differentiation into transformed pterygium fibroblast, epithelial cells, and endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

Song

Kang

et al. 2004

Eye

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Aims To evaluate the involvement of multipotential stem and progenitor cells in the pathogenesis of pterygium. Methods Paraffin-embedded and snap-frozen primary pterygium (n ¼ 10) were serially sectioned and analysed immunohistochemically to determine the expression level of AC133 (marker for the primitive haematopoietic progenitors), CD34 (marker for the haematopoietic progenitor cells and endothelium), c-Kit (marker for haematopoietic and stromal progenitor cells), and STRO-1 (a differentiation antigen present on bone marrow fibroblast cells and on various nonhaematopoietic progenitor cells). Results In all the primary pterygium, immunoreactivity of AC133 and STRO-1 was found in some of the epithelial and stromal cells, CD34 was observed in the vascular endothelium, and some scattered ovoidal cells were found in the subepithelial connective tissue. C-Kit was expressed mainly in the basal epithelium of the head portions, and some spindle-shaped stromal cells. There is no immunoreactivity of AC133, c-Kit, and STRO-1 in normal conjunctiva, whereas CD34 was mildly stained with vessel wall. Conclusion Multipotential stem and progenitor cells may be involved in the pathogenesis of pterygium through its differentiation into fibroblasts and vascular endothelial cells.

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“…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.…”

Section: Introductionmentioning

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

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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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Human Marrow-Derived Mesenchymal Stem Cells (MSCs) Express Hematopoietic Cytokines and Support Long-Term Hematopoiesis When Differentiated Toward Stromal and Osteogenic Lineages

Cited by 401 publications

References 13 publications

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium

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

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