Jie Xie

Human adipose-derived stem cells ameliorate cigarette smoke-induced murine myelosuppression via secretion of TSG-6

Objective: Bone marrow‐derived hematopoietic stem and progenitor cells (HSC/HPC) are critical to homeostasis and tissue repair. The aims of this study were to delineate the myelotoxicity of cigarette smoking (CS) in a murine model, to explore human adipose‐derived stem cells (hASC) as a novel approach to mitigate this toxicity, and to identify key mediating factors for ASC activities. Methods: C57BL/6 mice were exposed to CS with or without i.v. injection of regular or siRNA‐transfected hASC. For in vitro experiments, cigarette smoke extract was used to mimic the toxicity of CS exposure. Analysis of bone marrow HPC was performed both by flow cytometry and colony‐forming unit assays. Results: In this study, we demonstrate that as few as 3 days of CS exposure results in marked cycling arrest and diminished clonogenic capacity of HPC, followed by depletion of phenotypically defined HSC/HPC. Intravenous injection of hASC substantially ameliorated both acute and chronic CS‐induced myelosuppression. This effect was specifically dependent on the anti‐inflammatory factor TSG‐6, which is induced from xenografted hASC, primarily located in the lung and capable of responding to host inflammatory signals. Gene expression analysis within bone marrow HSC/HPC revealed several specific signaling molecules altered by CS and normalized by hASC. Conclusion: Our results suggest that systemic administration of hASC or TSG‐6 may be novel approaches to reverse CS‐induced myelosuppression. Stem Cells 2015;33:468–478

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model

The potential for beneficial effects of adipose‐derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors.

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28− T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28− (-28%), CD8+CD28− T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1−LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression.

Endovascular treatment of an iatrogenic superior mesenteric arteriovenous fistula after Nissen fundoplication

We present a case of a superior mesenteric arteriovenous fistula (SMAVF) diagnosed four years after index Nissen fundoplication and examine the associated imaging, clinical course, and surgical treatment followed by a review of the limited, available literature. From a transbrachial approach, a covered stent was successfully deployed in the superior mesenteric artery to exclude the fistula after confirmation of the site of pathology on both digital subtraction angiography and intravascular ultrasound. Follow-up imaging demonstrated continued exclusion of the anomalous fistula with complete resolution of his symptoms at both his postprocedure and 1-year follow-up visits. SMAVFs are usually encountered secondary to previous surgical dissection or trauma and presents with nondescript abdominal pain making early diagnosis difficult; however, they can be successfully treated with minimally-invasive stent exclusion.

Bone Marrow–Derived Cells: From the Laboratory to the Clinic

Abstract Bone marrow mononuclear cells (BMMNC) are enriched with a variety of angiogenic stem and progenitor cells, as well as mature hematopoietic cells that function synergistically to promote neovascularization. Delivery of BMMNC or its subpopulations have demonstrated marked effects on revascularization of ischemic tissue in preclinical models. Extensive phase-I and -II clinical trials in critical limb ischemia (CLI) patients have established the safety of BMMNC and showed promising effects of the cells to improve ischemic pain, ulcer size, pain-free walking distance, ABI, and TcPO2, while phase-III randomized control trials (RCT) are rapidly unfolding. This chapter introduces the concept of BMMNC and its subpopulations in the context of peripheral arterial disease. It also discusses the animal models of CLI in which mechanisms of bone marrow–derived cells were investigated. Finally, the progress in the clinical trials using BMMNC to treat CLI patients were summarized and the challenges were discussed.

Human Adipose-Derived Stem Cells Ameliorate Cigarette Smoke-Induced Murine Myelosuppression via Secretion of TSG-6: Adipose Stem Cells Ameliorate Smoking-Induced Myelosuppression Via TSG-6

Objective: Bone marrow‐derived hematopoietic stem and progenitor cells (HSC/HPC) are critical to homeostasis and tissue repair. The aims of this study were to delineate the myelotoxicity of cigarette smoking (CS) in a murine model, to explore human adipose‐derived stem cells (hASC) as a novel approach to mitigate this toxicity, and to identify key mediating factors for ASC activities. Methods: C57BL/6 mice were exposed to CS with or without i.v. injection of regular or siRNA‐transfected hASC. For in vitro experiments, cigarette smoke extract was used to mimic the toxicity of CS exposure. Analysis of bone marrow HPC was performed both by flow cytometry and colony‐forming unit assays. Results: In this study, we demonstrate that as few as 3 days of CS exposure results in marked cycling arrest and diminished clonogenic capacity of HPC, followed by depletion of phenotypically defined HSC/HPC. Intravenous injection of hASC substantially ameliorated both acute and chronic CS‐induced myelosuppression. This effect was specifically dependent on the anti‐inflammatory factor TSG‐6, which is induced from xenografted hASC, primarily located in the lung and capable of responding to host inflammatory signals. Gene expression analysis within bone marrow HSC/HPC revealed several specific signaling molecules altered by CS and normalized by hASC. Conclusion: Our results suggest that systemic administration of hASC or TSG‐6 may be novel approaches to reverse CS‐induced myelosuppression. Stem Cells 2015;33:468–478

Human Adipose-derived Stem Cells Ameliorate Cigarette Smoke-induced Murine Myelosuppression via TSG-6

Objective: Bone marrow‐derived hematopoietic stem and progenitor cells (HSC/HPC) are critical to homeostasis and tissue repair. The aims of this study were to delineate the myelotoxicity of cigarette smoking (CS) in a murine model, to explore human adipose‐derived stem cells (hASC) as a novel approach to mitigate this toxicity, and to identify key mediating factors for ASC activities. Methods: C57BL/6 mice were exposed to CS with or without i.v. injection of regular or siRNA‐transfected hASC. For in vitro experiments, cigarette smoke extract was used to mimic the toxicity of CS exposure. Analysis of bone marrow HPC was performed both by flow cytometry and colony‐forming unit assays. Results: In this study, we demonstrate that as few as 3 days of CS exposure results in marked cycling arrest and diminished clonogenic capacity of HPC, followed by depletion of phenotypically defined HSC/HPC. Intravenous injection of hASC substantially ameliorated both acute and chronic CS‐induced myelosuppression. This effect was specifically dependent on the anti‐inflammatory factor TSG‐6, which is induced from xenografted hASC, primarily located in the lung and capable of responding to host inflammatory signals. Gene expression analysis within bone marrow HSC/HPC revealed several specific signaling molecules altered by CS and normalized by hASC. Conclusion: Our results suggest that systemic administration of hASC or TSG‐6 may be novel approaches to reverse CS‐induced myelosuppression. Stem Cells 2015;33:468–478