Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

Siena, Rocco De; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela; Saldarelli, Marilisa; Saponaro, Vittorio; Martino, Carmela Di; Logrieco, G; Soleti, Antonio; Fiobellot, Simona; Madeddu, Paolo; Rossi, Giacomo; Ribatti, Doménico; Crovace, Antonio; Cristini, Silvia; Invernici, Gloria; Parati, Eugenio; Alessandri, Giulio

doi:10.1016/j.yexcr.2010.02.009

Cited by 25 publications

(23 citation statements)

References 35 publications

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“…A dermal fibroblast construct (3DFC), similar to the SVF construct used in the present study, has also exhibited increased gene expression of angiogenesis-related growth factors, such as HGF and VEGF (2,20). Additionally, intracardiac injection of fat-derived stromal cells (lacking the vascular elements included in the present study) mediated improvement of myocardial regeneration through the secretion of a wide spectrum of angiogenic factors, such as VEGF, HGF, and angiopoietin-1 (7). Therefore, it is likely that the cells on the SVF construct immediately secrete angiogenic factors after implantation and/or migrate and stabilize the repairing vessels in the infarct region by the secretion of angiogenic factors after a MI.…”

Section: Discussionmentioning

confidence: 70%

Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

LeBlanc

Touroo

Hoying

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve.

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Section: Discussionmentioning

confidence: 70%

Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

LeBlanc

Touroo

Hoying

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Several findings have demonstrated that hASCs are able to induce angiogenesis through a paracrine mechanism that, at least in part, could involve the secretion of HGF and VEFG [44,45]. Interestingly, it has recently been reported that rejuvenation or immortalization of adipose stromal cells may maximize their paracrine properties and improve their therapeutic potential.…”

Section: Discussionmentioning

confidence: 99%

Immortalization of human adipose-derived stromal cells: production of cell lines with high growth rate, mesenchymal marker expression and capability to secrete high levels of angiogenic factors

et al. 2014

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IntroductionHuman adipose-derived stromal cells (hASCs), due to their relative feasibility of isolation and ability to secrete large amounts of angiogenic factors, are being evaluated for regenerative medicine. However, their limited culture life span may represent an obstacle for both preclinical investigation and therapeutic use. To overcome this problem, hASCs immortalization was performed in order to obtain cells with in vitro prolonged life span but still maintain their mesenchymal marker expression and ability to secrete angiogenic factors.MethodshASCs were transduced with the human telomerase reverse transcriptase (hTERT) gene alone or in combination with either SV-40 or HPV E6/E7 genes. Mesenchymal marker expression on immortalized hASCs lines was confirmed by flow cytometry (FC), differentiation potential was evaluated by immunocytochemistry and ELISA kits were used for evaluation of angiogenic factors. Green fluorescent protein (GFP) gene transduction was used to obtain fluorescent cells.ResultsWe found that hTERT alone failed to immortalize hASCs (hASCs-T), while hTERT/SV40 (hASCs-TS) or hTERT/HPV E6/E7 (hASCs-TE) co-transductions successfully immortalized cells. Both hASCs-TS and hASCs-TE were cultured for up to one year with a population doubling level (PDL) up to 100. Comparative studies between parental not transduced (hASCs-M) and immortalized cell lines showed that both hASCs-TS and hASCs-TE maintained a mesenchymal phenotypic profile, whereas differentiation properties were reduced particularly in hASCs-TS. Interestingly, hASCs-TS and hASCs-TE showed a capability to secrete significant amount of HGF and VEGF. Furthermore, hASCs-TS and hASCs-TE did not show tumorigenic properties in vitro although some chromosomal aberrations were detected. Finally, hASCs-TS and hASCs-TE lines were stably fluorescent upon transduction with the GFP gene.ConclusionsHere we demonstrated, for the first time, that hASCs, upon immortalization, maintain a strong capacity to secrete potent angiogenic molecules. By combining hASCs immortalization and their paracrine characteristics, we have developed a “hybridoma-like model” of hASCs that could have potential applications for discovering and producing molecules to use in regenerative medicine (process scale-up).In addition, due to the versatility of these fluorescent-immortalized cells, they could be employed in in vivo cell-tracking experiments, expanding their potential use in laboratory practice.

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“…Two Ad-hMSC cultures, here named Ad09 and AdFV, were established from a male (34 years old) and a female (64 years old) donor, respectively. The Ad-hMSCs were isolated following a previously described procedure [20, 21]. …”

Section: Methodsmentioning

confidence: 99%

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

et al. 2017

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BackgroundMesenchymal stem/stromal cells (MSCs) represent an attractive tool for cell-based cancer therapy mainly because of their ability to migrate to tumors and to release bioactive molecules. However, the impact of MSCs on tumor growth has not been fully established. We previously demonstrated that murine MSCs show a strong tropism towards glioblastoma (GBM) brain xenografts and that these cells are able to uptake and release the chemotherapeutic drug paclitaxel (PTX), maintaining their tropism towards the tumor. Here, we address the therapy-relevant issue of using MSCs from human donors (hMSCs) for local or systemic administration in orthotopic GBM models, including xenografts of patient-derived glioma stem cells (GSCs).MethodsU87MG or GSC1 cells expressing the green fluorescent protein (GFP) were grafted onto the striatum of immunosuppressed rats. Adipose hMSCs (Ad-hMSCs), fluorescently labeled with the mCherry protein, were inoculated adjacent to or into the tumor. In rats bearing U87MG xenografts, systemic injections of Ad-hMSCs or bone marrow (BM)-hMSCs were done via the femoral vein or carotid artery. In each experiment, either PTX-loaded or unloaded hMSCs were used. To characterize the effects of hMSCs on tumor growth, we analyzed survival, tumor volume, tumor cell proliferation, and microvascular density.ResultsOverall, the AD-hMSCs showed remarkable tropism towards the tumor. Intracerebral injection of Ad-hMSCs significantly improved the survival of rats with U87MG xenografts. This effect was associated with a reduction in tumor growth, tumor cell proliferation, and microvascular density. In GSC1 xenografts, intratumoral injection of Ad-hMSCs depleted the tumor cell population and induced migration of resident microglial cells. Overall, PTX loading did not significantly enhance the antitumor potential of hMSCs. Systemically injected Ad- and BM-hMSCs homed to tumor xenografts. The efficiency of hMSC homing ranged between 0.02 and 0.5% of the injected cells, depending both on the route of cell injection and on the source from which the hMSCs were derived. Importantly, systemically injected PTX-loaded hMSCs that homed to the xenograft induced cytotoxic damage to the surrounding tumor cells.ConclusionshMSCs have a therapeutic potential in GBM brain xenografts which is also expressed against the GSC population. In this context, PTX loading of hMSCs seems to play a minor role.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0516-3) contains supplementary material, which is available to authorized users.

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Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

Cited by 25 publications

References 35 publications

Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

Immortalization of human adipose-derived stromal cells: production of cell lines with high growth rate, mesenchymal marker expression and capability to secrete high levels of angiogenic factors

Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

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