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TAMPA, FL, United States

Sanberg P.R.,University of South Florida | Park D.,University of South Florida | Kuzmin-Nichols N.,Saneron Ccel Therapeutics, Inc. | Cruz E.,Cryopraxis and Silvestre Laboratory | And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

Neovascularization is an integral process of inflammatory reactions and subsequent repair cascades in tissue injury. Monocytes/macrophages play a key role in the inflammatory process including angiogenesis as well as the defence mechanisms by exerting microbicidal and immunomodulatory activity. Current studies have demonstrated that recruited monocytes/macrophages aid in regulating angiogenesis in ischemic tissue, tumours and chronic inflammation. In terms of neovascularization followed by tissue regeneration, monocytes/macrophages should be highly attractive for cell-based therapy compared to any other stem cells due to their considerable advantages: non-oncogenic, non-teratogenic, multiple secretary functions including pro-angiogenic and growth factors, straightforward cell harvesting procedure and non-existent ethical controversy. In addition to adult origins such as bone marrow or peripheral blood, umbilical cord blood (UCB) can be a potential source for autologous or allogeneic monocytes/macrophages. Especially, UCB monocytes should be considered as the first candidate owing to their feasibility, low immune rejection and multiple characteristic advantages such as their anti-inflammatory properties by virtue of their unique immune and inflammatory immaturity, and their pro-angiogenic ability. In this review, we present general characteristics and potential of monocytes/macrophages for cell-based therapy, especially focusing on neovascularization and UCB-derived monocytes. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source


Borlongan C.V.,University of South Florida | Kaneko Y.,University of South Florida | Maki M.,Georgia Regents University | Yu S.-J.,University of South Florida | And 5 more authors.
Stem Cells and Development | Year: 2010

Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of "individually tailored" donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke. © Mary Ann Liebert, Inc. 2010. Source


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 140.38K | Year: 2007

DESCRIPTION (provided by applicant): Modulation of the inflammatory cascade by several diverse strategies including A immunization, non-steroidal anti-inflammatory drug (NSAID) administration, and manipulation of microglial activation states have all been shown to reduce Alzheimer disease (AD)-like pathology, and cognitive deficits in AD transgenic mouse models. Our recent study demonstrated amelioration of AD-like pathology in PSAPP (APPswe, PSEN1dE9) mice when multiply injected with low dose of Saneron's human umbilical cord blood cells mononuclear fraction (HUCBC, trademark name "U-CORD-CELLTM"), a well known immunomodulator. This was observed through marked reduction of A?/?-amyloid plaques and associated astrocytosis. In concert with this down-regulation of pro-inflammatory signaling, cultured microglia isolated from HUCBC-infused PSAPP mice demonstrated increased A? phagocytic activity, thus clearly demonstrating HUCBC's potential immunomodulatory property. Although a typical reduction in cerebral A? plaque burden has been associated with an improvement in cognition, regarded as the true sign of improvement in AD, our study did not address either the behavioral or the cognitive changes associated with HUCBC injections. Thus, in this proposal we would like to test if HUCBC infusion can promote a rescue of behavioral and cognitive deficits and correlate these changes with their pathological improvements in PSAPP mice. Furthermore, we also plan to infuse these mice with human adult mononuclear fractions to demonstrate specific need for HUCBC rather than the adult mononuclear cells in order to observe these immunomodulatory and therapeutic effects. Based on these combined lines of evidence and our recent study, we hypothesize that multiple low dose injections of U-CORD-CELL" into transgenic PSAPP mice will provide a rescue of behavioral deficits, which will be correlated with improvements in AD-like pathology. The goal of this proposal is to establish a strong, well-integrated research program based on recently established roles of Th1/Th2 immunity, HUCBC transplantation, and AD pathogenesis. This knowledge is used to rationalize U-CORD-CELL" as a potentially safe and effective immunomodulatory therapy for AD.Project Narrative - Relevance to public health. In summary, we hypothesize that multiple low dose injections of Saneron's human umbilical cord blood cells mononuclear fraction (HUCBC, trademark name U-CORD-CELL") into transgenic PSAPP mice will provide a rescue of behavioral deficits, which will be correlated with improvements in AD-like pathology. The goal of this proposal is to establish a strong, well-integrated research program based on recently established roles of Th1/Th2 immunity, HUCBC transplantation, and AD pathogenesis. This knowledge is used to rationalize U-CORD-CELL" as a potentially safe and effective immunomodulatory therapy for AD.


Patent
University of South Florida, Saneron Ccel Therapeutics, Inc. and Georgia Regents University | Date: 2011-05-13

A cell type that is a complete match of the transplant recipient appears as an optimal scenario to open treatment options to a large patient population with minimal complications. The use of autologous bone marrow or umbilical cord blood has been proposed as a good source of stem cells for cell therapy. Menstrual blood is found to be another important source of stem cells. Assays of cultured menstrual blood reveal that they express embryonic like-stem cell phenotypic markers and neuronal phenotypic markers under appropriate conditioned media. Oxygen glucose deprivation stroke models show that OGD-exposed primary rat neurons, co-cultured with menstrual blood-derived stem cells or exposed to the media from cultured menstrual blood, exhibited significantly reduced cell death. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 184.25K | Year: 2005

DESCRIPTION (provided by applicant): Transplantation of human umbilical cord stem cells (hUCBC) has been shown to be effective in limiting infarct size and in the preservation of left ventricular function and anatomy in a rat model. These effects have been present in studies both utilizing and not utilizing immunosuppression. Whether immunosuppression will be required in a large animal model is unknown, as is the efficacy of transplantation of hUCBC in a large animal model. This data is critical in order to determine the risk:benefit ratio of this therapy, especially if immunosuppression is required; and in order to move this therapy into human clinical trials for the treatment of myocardial infarction and prevention of congestive heart failure which affects over 5 million patients in the U.S. This study is specifically designed to evaluate the effects of hUCBC transplantation following myocardial infarction on left ventricular function and anatomy and determine the necessity of immunosuppression in a porcine model. Forty-two animals will be studied; 6 animals will serve as controls (no myocardial infarction) and 36 animals will undergo myocardial infarction (MI). The MI group will consist of three (12 animals each) different treatment modalities (Group 1-no treatment, Group 2-treatment with Isolyte media injection into the infarct border zone, and Group 3-treatment with hUCBC injection into the infarct zone). Six animals in each treatment group will receive immunosuppression and six will receive no immunosuppression. Those animals that are designated for immunosuppression will receive cyclosporine 10 mg/kg twenty-four hours preoperatively and every day subsequently until sacrificed. The randomization will be blinded to pathologists, sonographers, and echocardiogram interpreters. LV function will be evaluated by echocardiography and invasive monitoring at 1, 2, and 4 wks and 2, 3, and 4 months. Animals will be sacrificed following evaluation and the heart tissue will be analyzed for infarct size, hUCBC engraftment, immunorejection, cardiac phenotype (using immunohistochemistry), and stem-cell derived endothelial cells. It is anticipated that the results from this study will assist in planning further studies for determination of the appropriate dosage, route, and timing of administration of hUCBC for the treatment of acute myocardial infraction to preserve left ventricular function and anatomy and prevent the development of congestive heart failure.

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