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Sahoo S.,Feinberg Cardiovascular Research Institute | Losordo D.W.,Feinberg Cardiovascular Research Institute | Losordo D.W.,Neostem, Inc.
Circulation Research | Year: 2014

Myocardial infarction is a leading cause of death among all cardiovascular diseases. The analysis of molecular mechanisms by which the ischemic myocardium initiates repair and remodeling indicates that secreted soluble factors are key players in communication to local and distant tissues, such as bone marrow. Recently, actively secreted membrane vesicles, including exosomes, are being recognized as new candidates with important roles in intercellular and tissue-level communication. In this review, we critically examine the emerging role of exosomes in local and distant microcommunication mechanisms after myocardial infarction. A comprehensive understanding of the role of exosomes in cardiac repair after myocardial infarction could bridge a major gap in knowledge of the repair mechanism after myocardial injury. © 2014 American Heart Association, Inc. Source

Cooke J.P.,Houston Methodist Research Institute | Losordo D.W.,Neostem, Inc.
Circulation Research | Year: 2015

The age-adjusted prevalence of peripheral arterial disease in the US population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may successfully reperfuse the limbs of certain patients with peripheral arterial disease. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and procedural revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of stem/progenitor cell therapy. The purpose of this review is to provide an outline of the preclinical basis for angiogenic and stem cell therapies, review the clinical research that has been done, summarize the lessons learned, identify gaps in knowledge, and suggest a course toward successfully addressing an unmet medical need in a large and growing patient population. © 2015 American Heart Association, Inc. Source

Hall S.R.R.,Neostem, Inc. | Jiang Y.,Neostem, Inc. | Leary E.,Neostem, Inc. | Yavanian G.,Neostem, Inc. | And 3 more authors.
Stem Cells Translational Medicine | Year: 2013

The method of isolation of bone marrow (BM) mesenchymal stem/stromal cells (MSCs) is a limiting factor in their study and therapeutic use. MSCs are typically expanded fromBMcells selected on the basis of their adherence to plastic, which results in a heterogeneous population of cells. Prospective identification of the antigenic profile of the MSC population(s) inBMthat gives rise to cells with MSC activity in vitro would allow the preparation of very pure populations of MSCs for research or clinical use. To address this issue, we used polychromatic flow cytometry and counterflow centrifugal elutriation to identify a phenotypically distinct population of mesenchymal stem/progenitor cells (MSPCs) within human BM. The MSPC activity resided within a population of rare, small CD45-CD73+CD90+CD105+ cells that lack CD44, an antigen that is highly expressed on cultureexpanded MSCs. In culture, these MSPCs adhere to plastic, rapidly proliferate, and acquire CD44 expression. They form colony forming units-fibroblast and are able to differentiate into osteoblasts, chondrocytes, and adipocytes under defined in vitro conditions. Their acquired expression of CD44 can be partially downregulated by treatment with recombinant human granulocyte-colony stimulating factor, a response not found in BM-MSCs derived from conventional plastic adherence methods. These observations indicate that MSPCs within human BM are rare, small CD45-CD73+CD90+CD105+ cells that lack expression of CD44. These MSPCs give rise to MSCs that have phenotypic and functional properties that are distinct from those of BM-MSCs purified by plastic adherence. © AlphaMed Press 2013. Source

Wang X.,Hospital 85 Peoples Liberation | Bayer M.E.,Neostem, Inc. | Chen X.,Shanghai Renji Hospital | Fredrickson C.,Neostem, Inc. | And 10 more authors.
Journal of Surgical Oncology | Year: 2015

Background and Objectives Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis-B or -C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long-term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high-risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis. Methods Previously untreated HCC patients with a solitary lesion >5cm, or three lesions with at least one >3cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC-TC. After one course of trans-arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC suspended in granulocyte-macrophage colony stimulating factor were administered. Patients were monitored for eight weeks. Results HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA. Conclusion Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned. © 2015 Wiley Periodicals, Inc. Source

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