Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells

D’Elia, Piera; Ionta, Vittoria; Chimenti, Isotta; Angelini, Francesco; Miraldi, Fabio; Pala, Andrea Norcini; Messina, Elisa; Giacomello, Alessandro

doi:10.1155/2013/190178

Cited by 16 publications

(10 citation statements)

References 37 publications

(56 reference statements)

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“…In particular, the strongest array signal was that of EGF, together with highly detectable levels of other growth factors such as insulin‐like growth factor‐1 (IGF‐1), hepatocyte growth factor (HGF), and glial cell‐derived neurotrophic factor (GDNF). Binding proteins, such as insulin‐like growth factor‐binding protein (IGFBPs), that regulate growth factor availability and are suggested to play roles in stem cell biology [, ], were produced as well. PSs secreted chemokines, such as IL‐8, MCP‐1, MIP‐1α, and RANTES; and proteins, such as osteoprotegerin, with a well‐known immunomodulatory function.…”

Section: Resultsmentioning

confidence: 99%

Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

Chimenti

Pagano

Angelini

et al. 2016

Stem Cells Translational Medicine

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Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied to healthy human lung tissue. We aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of LPCs to create an ideal niche‐like microenvironment. The influence of different substrates (i.e., fibronectin, gelatin, laminin) and the impact of a three‐dimensional/two‐dimensional (3D/2D) culture switch on the biology of LPCs isolated as lung spheroids (LSs) from normal adult human lung biopsy specimens were investigated. We applied a spheroid culture system as the selective/inductive step for progenitor cell culture, as described in many biological systems. The data showed a niche‐like proepithelial microenvironment inside the LS, highly sensitive to the 3D culture system and significantly affecting the phenotype of adult LPCs more than culture substrate. LSs favor epithelial phenotypes and LPC maintenance and contain cells more responsive to specific commitment stimuli than 2D monolayer cultures, while secreting a distinctive set of paracrine factors. We have shown for the first time, to our knowledge, how culture as 3D LSs can affect LPC epithelial phenotype and produce strong paracrine signals with a distinctive secretomic profile compared with 2D monolayer conditions. These findings suggest novel approaches to maintain ex vivo LPCs for basic and translational studies. Stem Cells Translational Medicine 2017;6:767–777

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Section: Resultsmentioning

confidence: 99%

Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

Chimenti

Pagano

Angelini

et al. 2016

Stem Cells Translational Medicine

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“…are upregulated in PL-cultured ADMSCs, but they were not induced by cardiosphere-conditioned media exposure. This indicates the relevance of the specific stimulus on the outcome of the phenotypical commitment, most likely due to the different composition in the type and concentration of soluble factors within the two microenvironments [ 25 – 27 ]. Besides, although a different study has already suggested the potential of PL to promote cardiac phenotype of ADMSCs [ 12 ], the commitment was driven by a combination of PL and 5-azacytidine (a widely used, although controversial, cardiac transdifferentiation agent [ 14 ]), thus masking the real efficacy of PL.…”

Section: Resultsmentioning

confidence: 99%

The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

Siciliano

Chimenti

Bordin

et al. 2015

BioMed Research International

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Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

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“…PAPP‐A‐mediated IGF‐I release via proteolytic cleavage of IGFBP‐4 contributed to angiogenesis and heart tissue regeneration postinjury (D'Elia et al. ; Barile et al. ).…”

Section: Discussionmentioning

confidence: 99%

Cellular characterization of human epicardial adipose tissue: highly expressed PAPP-A regulates insulin-like growth factor I signaling in human cardiomyocytes

et al. 2019

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Little is known about the cellular biology of fat surrounding the human heart. In this study, we obtained paired samples of epicardial fat, the visceral fat depot attached to the heart, and subcutaneous skin fat from patients undergoing open heart surgery to test the hypothesis that human epicardial fat cells differentially express bioactive molecules that have the potential to affect cardiac function. First, we characterized the free fatty acids (FFAs), adipocytokines, and growth factors secreted by isolated adipocytes and preadipocytes in cell culture. There was little to distinguish the fat cell secretory products in terms of FFAs and adipocytokines. The most striking finding was that preadipocytes from epicardial adipose tissue expressed high levels of pregnancy‐associated plasma protein‐A ( PAPP ‐A), a novel metalloproteinase that enhances local insulin‐like growth factor ( IGF ) action through cleavage of inhibitory IGF binding protein‐4 ( IGFBP ‐4). PAPP ‐A levels were 15‐fold higher in conditioned medium from epicardial preadipocytes than from subcutaneous preadipocytes ( P < 0.0001). PAPP ‐A was not expressed in mature adipocytes. Next we determined whether PAPP ‐A could affect IGF ‐I signaling in a human cardiomyocyte cell line. IGF ‐I activated receptor‐mediated auto‐phosphorylation, and this was blocked by wild‐type and protease‐resistant IGFBP ‐4. Addition of PAPP ‐A induced cleavage of wild‐type, but not protease‐resistant, IGFBP ‐4 thereby restoring IGF ‐I action. A proteolytically defective PAPP ‐A had no effect. IGF ‐I receptor‐mediated signaling through the phosphatidylinositol 3‐kinase pathway was similarly inhibited by IGFBP ‐4 and restored by PAPP ‐A. Thus, human epicardial fat cells differentially express PAPP ‐A, which has the potential to affect IGF signaling in the heart.

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Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells

Cited by 16 publications

References 37 publications

Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

Cellular characterization of human epicardial adipose tissue: highly expressed PAPP-A regulates insulin-like growth factor I signaling in human cardiomyocytes

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