Direct Myocardial Implantation of Human Fetal Stem Cells in Heart Failure Patients: Long-term Results
ABSTRACT End-stage heart failure (HF) is refractory to current standard medical therapy, and the number of donor hearts is insufficient to meet the demand for transplantation. Recent studies suggest autologous stem cell therapy may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac function and clinical status. Although human fetal-derived stem cells (HFDSCs) have been studied for the treatment of a variety of conditions, no clinical studies have been reported to date on their use in treating HF. We sought to determine the efficacy and safety of HFDSC treatment in HF patients.
Direct myocardial transplantation of HFDSCs by open-chest surgical procedure was performed in 10 patients with HF due to nonischemic, nonchagasic dilated cardiomyopathy. Before and after the procedure, and with no changes in their preoperative doses of medications (digoxin, furosemide, spironolactone, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers), patients were assessed for New York Heart Association (NYHA) class, performance in the exercise tolerance test (ETT), ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) via transthoracic echocardiography, performance in the 6-minute walk test, and performance in the Minnesota congestive HF test. All 10 patients survived the operation. One patient had a stroke 3 days after the procedure, and although she later recovered, she was unable to perform the follow-up tests. Another male patient experienced pericardial effusion 3 weeks after the procedure. Although it resolved spontaneously, the patient abandoned his control tests and died 5 months after the procedure. An autopsy of the myocardium suggested that new young cells were present in the cardiomyocyte mix. At 40 months, the mean (+/-SD) NYHA class decreased from 3.4 +/- 0.5 to 1.33 +/- 0.5 (P = .001); the mean EF increased 31%, from 26.6% +/- 4% to 34.8% +/- 7.2% (P = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from 6.85 +/- 0.6 cm to 5.80 +/- 0.58 cm (P < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 +/- 113.1 seconds to 360 +/- 0 seconds (P = .01); the mean distance increased 64.4%, from 284.4 +/- 144.9 m to 468.2 +/- 89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 +/- 27.3 to 6 +/- 5.9 (P < .001).
Although these initial findings suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac function in HF patients at 40 months, more clinical research is required to confirm these observations.
Conference Paper: WETICE 2003 Eight Enterprise Security (ES) workshop report[Show abstract] [Hide abstract]
ABSTRACT: The WETICE Enterprise Security (ES) workshop had a total of seventeen full papers and one poster paper presented. The workshop presentation fell into four major sections: Trust Management - five papers, Role based access control - five papers, Cryptography - three papers, and Software and Network Security - five papers. Based from the papers' discussions and the large amount of focus on Trust, Risk and RBAC, this problem should continue to be focused on and addressed at the next ES workshop.Enabling Technologies: Infrastructure for Collaborative Enterprises, 2003. WET ICE 2003. Proceedings. Twelfth IEEE International Workshops on; 07/2003
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ABSTRACT: Human colorectal cancer (CRC), the second largest cause of tumor-related death in Western countries, represents a paradigm for the now well-established connections between inflammation and cancer. In this study, we investigated which inflammatory mediators are mostly expressed in the microenvironment of human CRC. The RNA profile of a large panel of inflammatory genes, in particular chemokines and chemokine receptors, was analyzed in eight surgical tumor samples and in paired normal tissues from CRC patients. We employed an "inflammatory gene card" (TaqMan Low Density Array by Applied Biosystem), designed by our group, containing probes for 24 chemokines and 17 chemokine receptors. Several chemokines were strongly upregulated in the tumor microenvironment, most frequently CCL4 and CCL5, chemotactic for monocytes/macrophages and T cells, and the corresponding receptors CCR1 and CCR5; the angiogenic chemokines CXCL1 and CXCL8, and the receptor CXCR2. The antiangiogenic chemokines CXCL9 and CXCL10 were also expressed, but in the absence of the receptor CXCR3. Selected results have been confirmed in a larger number of samples. The levels of mRNA CXCL8 were significantly associated with the levels of osteopontin, a matrix-associated protein that shares with chemokines important functions such as induction of cell migration and survival, and modulation of the neoangiogenesis. Overall these results could be helpful to identify the most relevant inflammatory pathways present in CRC tumors and to build a solid rationale for future therapeutic interventions based on anti-inflammatory strategies.Methods in enzymology 02/2009; 460:105-21. DOI:10.1016/S0076-6879(09)05205-7 · 2.09 Impact Factor
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ABSTRACT: In view of the only modest functional and anatomical improvements achieved by bone marrow-derived cell transplantation in patients with heart disease, the question was addressed whether the intracoronary, transcoronary-venous, and intramyocardial delivery routes are adequate. It is hypothesized that an intrapericardial delivery of stem cells or activators of resident cardiac stem cells increases therapeutic benefits. From such an intrapericardial depot, cells or modulating factors, such as thymosin β4 or Ac-SDKP, are expected to reach the myocardium with sustained kinetics. Novel tools which provide access to the pericardial space even in the absence of pericardial effusion are, therefore, described. When the pericardium becomes attached to the suction head (monitored by an increase in negative pressure), the pericardium is lifted from the epicardium ("AttachLifter"). The opening of the suction head ("Attacher") is narrowed by flexible clamps which grab the tissue and improve the vacuum seal in the case of uneven tissue. A ridge, i.e.,"needle guidance", on the suction head excludes injury to the epicardium, whereby the pericardium is punctured by a needle which resides outside the suction head. A fiberscope can be used to inspect the pericardium prior to puncture. Based on these procedures, the role of the pericardial space and the presence of pericardial effusion in cardiac regeneration can be assessed.Herz 10/2010; 35(7):458-65. DOI:10.1007/s00059-010-3382-7 · 0.69 Impact Factor