Comparative Analysis of Paracrine Factor Expression in Human Adult Mesenchymal Stem Cells Derived from Bone Marrow, Adipose, and Dermal Tissue

Hsiao, Sarah; Asgari, Azar; Lokmic, Zerina; Sinclair, Rodney; Dusting, Gregory J.; Lim, Shiang Y.; Dilley, Rodney J.

doi:10.1089/scd.2011.0674

Cited by 362 publications

(312 citation statements)

References 73 publications

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“…To investigate the proangiogenic paracrine capacity of W8B2 1 CRSCs, a Matrigel endothelial network assay was used [17]. In comparison with the control group, HCMEC cultured in conditioned medium harvested from W8B2 1 CRSCs showed a significant improvement in tubular network formation on Matrigel in term of number of complete ring formed and branching points but not the average length of network formed.…”

Section: Conditioned Medium Derived From W8b2 1 Crscs Promotes Angiogmentioning

confidence: 99%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2 1 CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2 1 CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2 1 CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1, or WT1. W8B2 1 CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2 1 CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2 1 CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (~40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2 1 CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67 1 cTnT 1 cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163 1 cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2 1 CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction. STEM CELLS 2015;33:3100-3113 SIGNIFICANCE STATEMENTWe have isolated a new type of adult stem cell from human heart tissue, which carries markers different from known cardiac resident stem cells. These cells can be rapidly expanded and have powerful regenerative effects when injected into the hearts of rats after heart attack, such that they greatly improve cardiac performance compared with controls that have also suffered heart attack. We showed these cells protect other cells from dying and promote growth of blood vessels, actions which assist cardiac regeneration. Importantly, their protective actions in this regard are superior to those of other adult stem cells that have shown some benefit in clinical trials after heart attack. These new stem cells have great potential for repairing the heart, and could be derived from the individual patients in need, avoiding any problem of immunorejection.

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Section: Conditioned Medium Derived From W8b2 1 Crscs Promotes Angiogmentioning

confidence: 99%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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“…MSCs also secrete various cytokines and angiogenic mediators that repair damaged tissues (10). A previous comparative study has indicated that the umbilical cord (UC) is an excellent alternative to bone marrow (BM) as a source of MSCs for cell therapy (11).…”

Section: Introductionmentioning

confidence: 99%

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Dong

Qing-shen

et al. 2016

Molecular Medicine Reports

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Abstract. Mesenchymal stem cells (MSCs) are an attractive cellular source for cell-based therapy, tissue engineering and regenerative medicine. However, the use of MSCs is limited by their low incorporation rate in the graft environment. The majority of cells are lost from the graft within 1 month, due to reduced microenvironment or local inflammation at the graft site. The extracellular matrix (ECM) may assist the survival and expansion of MSCs. The present study aimed to identify an effective approach to increase ECM expression levels by MSCs in order to enhance the therapeutic effect and survival rate of MSCs at the injury site. The concentration-dependent effect of transforming growth factor (TGF)-β1 on human umbilical cord (hUC)-MSC proliferation and expression of ECM genes was investigated. MSCs were successfully isolated, cultured and expanded from hUC. A low concentration of TGF-β1 (0.1 ng/ml) exhibited the optimal effect on hUC-MSC proliferation and markedly stimulated the expression of ECM genes, particularly fibronectin (FN). Furthermore, treatment with TGF-β1 caused no alteration in the immunophenotype and differentiation capacity of MSCs. In vivo experiments in rats demonstrated that intravenous injection of control UC-MSCs or TGF-β1-pre-treated UC-MSCs reduced the severity of lipopolysaccharide-induced lung injury, assessed using histology, measurements of the wet-dry lung weight ratio, and neutrophil count and protein concentration in bronchoalveolar lavage fluid. However, the short-term (48 h) therapeutic effects of untreated and TGF-β1-pre-treated UC-MSCs were similar. The survival of MSCs in damaged lungs, determined by Sry gene expression levels, were significantly increased in MSCs pre-treated with TGF-β1. In conclusion, pre-treatment of MSCs with a low concentration of TGF-β1 enhanced the expression of ECM components, particularly FN, thus, improving the survival and potential therapeutic benefits of MSCs. Pre-treatment of MSCs with TGF-β1 may prolong the effective therapy time and represent an efficient therapeutic approach for tissue repair.

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“…AT is composed of adipocytes and various cell types among which are a population of multipotent progenitors, termed adipose stromal cells (ASCs) [4]. ASCs display similar but not identical features with their bone marrow (BM) counterparts, mesenchymal stromal cells (MSCs) [5][6][7][8][9]. Like MSCs, ASCs are endowed with multilineage mesodermal differentiation potentials and exhibit extensive paracrine and immune-modulatory properties [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

et al. 2013

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Adipose tissue (AT) has become accepted as a source of multipotent progenitor cells, the adipose stromal cells (ASCs). In this regard, considerable work has been performed to harvest and characterize this cell population as well as to investigate the mechanisms by which transplanted ASCs mediate tissue regeneration. In contrast the endogenous release of native ASCs by AT has been poorly investigated. In this work, we show that native ASCs egress from murine AT. Indeed, we demonstrated that the release of native ASCs from AT can be evidenced both using an ex vivo perfusion model that we set up and in vivo. Such a mobilization process is controlled by CXCR4 chemokine receptor. In addition, once mobilized from AT, circulating ASCs were found to navigate through lymph fluid and to home into lymph nodes (LN). Therefore, we demonstrated that, during the LN activation, the fat depot encapsulating the activated LN releases native ASCs, which in turn invade the activated LN. Moreover, the ASCs invading the LN were visualized in close physical interaction with podoplanin and ER-TR7 positive structures corresponding to the stromal network composing the LN. This dynamic was impaired with CXCR4 neutralizing antibody. Taken together, these data provide robust evidences that native ASCs can traffic in vivo and that AT might provide stromal cells to activated LNs. STEM CELLS

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Comparative Analysis of Paracrine Factor Expression in Human Adult Mesenchymal Stem Cells Derived from Bone Marrow, Adipose, and Dermal Tissue

Cited by 362 publications

References 73 publications

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation

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