Bone Marrow Oct3/4
            <sup>+</sup>
            Cells Differentiate Into Cardiac Myocytes via Age-Dependent Paracrine Mechanisms

Pallante, Benedetta A.; Duignan, Inga; Okin, Daniel; Chin, Andrew I.; Bressan, Michael; Matsukawa, Takashi; Edelberg, Jay M.

doi:10.1161/01.res.0000253487.02398.85

Cited by 63 publications

(50 citation statements)

References 55 publications

(66 reference statements)

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“…Troponin T + cells started to form at the periphery of cell clusters after 7 days and chronotropic activity was observed after 14 days of differentiation. Importantly, efficiency of cardiac differentiation of Oct3/4 + cells declined with age (12). The differentiation pattern of BM-derived cardiomyocytes was similar to that observed in embryonic cell-derived cardiomyocytes (12,13).…”

Section: Discussionsupporting

confidence: 68%

“…Importantly, efficiency of cardiac differentiation of Oct3/4 + cells declined with age (12). The differentiation pattern of BM-derived cardiomyocytes was similar to that observed in embryonic cell-derived cardiomyocytes (12,13). Pallante et al confirmed that the cardiogenic Oct3/4 + cells were rare (0.05%) within BM cells localized in the osteoblastic niche.…”

Section: Discussionmentioning

confidence: 67%

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Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Wojakowski

Tendera²,

Kucia³

et al. 2010

Int J Oncol

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Abstract.VSELs are a population of rare Oct-4 + CXCR4 + CD133 + lin -CD45 -cells that are deposited during early embryogenesis in developing organs/tissues as a reserve population of pluripotent stem cells for regeneration. We reported recently that they are mobilized into peripheral blood during acute myocardial infarction (AMI) in mice and humans. However, although freshly isolated VSELs in experimental AMI mouse models improve cardiac function, the number of these cells is limited and an ex vivo expansion strategy is needed to employ these cells more efficiently for cardiac regeneration. The aim of this study was to establish an efficient method to expand ex vivo BM-derived very small embryonic-like stem cells (VSELs) into cardiomyocytes. VSELs, highly purified by FACS from the bone marrow of GFP transgenic mice, were expanded over C2C12 cell line myoblasts and exposed to cardiac differentiating media. The changes in gene expression during cardiac differentiation of VSELs were evaluated by RTQ-PCR, immunostaining and gene array analysis. We developed an efficient, two-step, ex vivo expansion/differentiation model of BM-derived VSELs into cardiomyocytes. First, purified GFP + VSELs are plated over C2C12 murine cell line myoblasts, where they expand and differentiate into characteristic spheres. Subsequently, cells from these spheres are expanded on cardiac differentiating media into cardiomyocytes. This study demonstrates that murine BM-derived VSELs can be efficiently expanded in vitro and differentiated into cardiomyocytes.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 67%

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Wojakowski

Tendera²,

Kucia³

et al. 2010

Int J Oncol

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“…At the same time, another independent group reported that BM cells may also be a source of Oct-4 ϩ male germ cells . Finally, as recently demonstrated, BM cells may form culture aggregates of Oct3/4 ϩ cells, which in in vitro cultures in the presence of platelet derived growth factor, may differentiate into cardiomyocytes (Pallante et al, 2007).…”

Section: Further Evidence For a Presence Of Oct-4؉ Cells In Bmmentioning

confidence: 64%

“…Stem cells that express early embryonic stem cell markers, including Oct-4, Nanog, and SSEA-1, had been identified in BM in several potential multipotent/PSC isolated from the BM or CB such as VSELs (Kucia et al, 2006b, MSC (Colter et al, 2001;Pochampally et al, 2004), MAPC (Jiang et al, 2002), MIAMI (DЈIp-polito et al, 2004), USSC (Kogler et al, 2004), and precursors of oocytes/ spermatogonia and precursors of shuttling between BM and heart cardiomyocytes (Johnson et al, 2005;Nayernia et al, 2006;Pallante et al, 2007). It is very likely that several investigators using different isolation strategies described the same populations of stem cells but gave them different names according to circumstance.…”

Section: Presence Of Oct-4 ؉ Stem Cells In the Bmmentioning

confidence: 99%

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

Kucia

Wan

Ratajczak

2007

Developmental Dynamics

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Data from our and other laboratories provide evidence that bone marrow (BM) contains a population of stem cells that expresses early developmental markers such as (1) stage-specific embryonic antigen (SSEA) and (2) transcription factors Oct-4 and Nanog. These are the markers characteristic for embryonic stem cells, epiblast stem cells, and primordial germ cells (PGC). The presence of these stem cells in adult BM supports the concept that this organ contains some population of pluripotent stem cells that is deposited in embryogenesis during early gastrulation. We hypothesize that these cells could be direct descendants of the germ lineage that, to pass genes on to the next generations, has to create soma and, thus, becomes a "mother lineage" for all somatic cell lineages present in the adult body. Germ potential is established after conception in totipotent zygotes and retained in blastomeres of morula, cells from the inner cell mass of blastocyst, epiblast, and population of PGC. We will present a concept that SSEA ؉ Oct-4 ؉ Nanog ؉ cells identified in BM could be descendants of epiblast cells as well as some rare migrating astray PGC. Developmental Dynamics 236:3309 -3320, 2007.

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“…C-Kit, the transmembrane tyrosine kinase receptor for stem cell factor, is required for melanocyte and mast cell development, hematopoiesis and the differentiation of spermatogonial stem cells. 23 c-Kit is also transiently expressed in cardiomyocyte precursors during development and in a rare cell population in the normal adult heart. Li et al 24 demonstrated that in the heart, c-Kit is expressed not only by cardiac stem cells but also by cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

et al. 2010

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Statins exert pleiotropic effects, including antioxidative and cellular protective effects. Endogenous adrenomedullin (AM) induces anti-inflammatory, anti-fibrotic and proangiogenic effects. We examined the effects of simvastatin on cardiac fibrosis and apoptosis in AM heterozygous knockout (AM +/À ) mice treated with angiotensin (Ang) II and high salt loading. Seven-weekold AM +/À mice were infused with Ang II while on a high-salt diet with or without simvastatin for 2 weeks. Hearts were stained by hematoxylin-eosin or Masson's trichrome, and were immunostained with isolectin B 4 and a-smooth muscle actin antibodies. Expression of c-Kit and Sca-1 messenger RNA (mRNA) was evaluated by real-time PCR analysis. Apoptotic cells in hearts were identified by terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL) staining. Hearts from Ang II/salt loading AM +/À mice showed marked perivascular fibrosis around coronary arteries. Treatment with simvastatin significantly inhibited the fibrosis around coronary arteries in Ang II/salt-loading AM +/À mice. Expression of c-Kit and Sca-1 mRNAs in hearts from Ang II/salt-loading AM +/À mice was significantly lower than in hearts from wild-type mice. Treatment with simvastatin significantly increased the suppressed expression of c-Kit and Sca-1 mRNAs. In addition, treatment with simvastatin significantly increased the number of isolectin B 4 -positive capillary arteries in hearts from Ang II/salt-loading AM +/À mice. Ang II/high salt significantly increased apoptotic cells in hearts from AM +/À mice; this trend was reversed by treatment with simvastatin. Thus, statins have potent cardioprotective effects that may be associated with anti-fibrotic, proangiogenic and anti-apoptotic effects in Ang II/salt-loading AM +/À mice.

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Bone Marrow Oct3/4 ⁺ Cells Differentiate Into Cardiac Myocytes via Age-Dependent Paracrine Mechanisms

Abstract: Abstract-The mechanisms that govern the capacity of the bone marrow stem cells to generate cardiac myocytes are stillunknown. Herein we demonstrate that the cardiomyogenic potential of bone marrow-derived Oct3/4 ϩ

Cited by 63 publications

References 55 publications

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

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Bone Marrow Oct3/4 + Cells Differentiate Into Cardiac Myocytes via Age-Dependent Paracrine Mechanisms

Abstract: Abstract-The mechanisms that govern the capacity of the bone marrow stem cells to generate cardiac myocytes are stillunknown. Herein we demonstrate that the cardiomyogenic potential of bone marrow-derived Oct3/4 ϩ

Cited by 63 publications

References 55 publications

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Cardiomyocyte differentiation of bone marrow-derived Oct-4+CXCR4+SSEA-1+ very small embryonic-like stem cells

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

Protective effects of statin on cardiac fibrosis and apoptosis in adrenomedullin-knockout mice treated with angiotensin II and high salt loading

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Bone Marrow Oct3/4 ⁺ Cells Differentiate Into Cardiac Myocytes via Age-Dependent Paracrine Mechanisms