TAMPA, FL, United States

Saneron Ccel Therapeutics, Inc.

www.saneron-ccel.com
TAMPA, FL, United States
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Sanberg P.R.,University of South Florida | Eve D.J.,University of South Florida | Willing A.E.,University of South Florida | Garbuzova-Davis S.,University of South Florida | And 5 more authors.
Cell Transplantation | Year: 2011

Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells. Copyright © 2011 Cognizant Comm. Corp. All rights reserved.


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.


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.


Gonzales-Portillo G.S.,University of South Florida | Sanberg P.R.,University of South Florida | Franzblau M.,University of South Florida | Gonzales-Portillo C.,University of South Florida | And 4 more authors.
Cell Transplantation | Year: 2014

Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood-brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy. © 2014 Cognizant Comm. Corp.


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.


Jiang L.,University of South Florida | Womble T.,University of South Florida | Saporta S.,University of South Florida | Chen N.,University of South Florida | And 4 more authors.
Stem Cells and Development | Year: 2010

When human umbilical cord blood (HUCB) cells are systemically administered following middle cerebral artery occlusion (MCAO) in rats, they produce a reduction in infarct size resulting in recovery of motor function. Rats receiving HUCB cells have a less severe inflammatory response compared to MCAO stroke rats. The purpose of this study was to determine the interaction between HUCB cells and the main resident immune cells of the brain (microglia) under normoxic and hypoxic conditions in vitro. Primary microglial cultures were incubated for 2 h in no oxygen (95% N, 5% CO2) and low glucose (1%) media. Mononuclear HUCB cells were added to half the cultures at the beginning of the hypoxia conditions. Microglial viability was determined using fluorescein diacetate/propidium iodide (FDA/PI) labeling and cytokine expression using ELISA. In some studies, CD11b+ or CD19+ cells isolated from the HUCB mononuclear fraction with magnetic antibody cell sorting (MACS) were used instead of the mononuclear fraction. Co-culturing mononuclear HUCB cells with microglia decreased viability of the microglia during hypoxia. In the microglial monocultures, hypoxia significantly increased release of IL-1β compared to normoxia, while adding HUCB cells in the hypoxia condition decreased IL-1β concentrations to the same level as in the normoxia monocultures. Both CD11b+ and CD19+ HUCB cells decreased microglial viability during normoxia and hypoxia. Our data suggest that HUCB cells may produce a soluble factor that decreases viability of microglia. © 2010 Mary Ann Liebert, Inc.


Chen N.,University of South Florida | Newcomb J.,University of South Florida | Garbuzova-Davis S.,University of South Florida | Sanberg C.D.,Saneron Ccel Therapeutics, Inc. | And 3 more authors.
Aging and Disease | Year: 2010

In experimental models of central nervous system (CNS) aging, injury and disease, administering human umbilical cord blood (HUCB) cells induce recovery, most likely by interacting with multiple cellular processes. The aim of this study was to examine whether the HUCB cells produce trophic factors that may enhance survival and maturation of hippocampal neurons in an in vitro test system. We co-cultured the mononuclear fraction of HUCB cells with hippocampal neurons isolated from either young (7-months of age) or aging (21 month of age) rat brain for 14, 21, 28, 35 and 42 days in vitro (DIV), respectively. Immunocytochemistry was then employed to identify neurons (MAP2+) and glial cells (GFAP+) as well as arborization of neurites. The average number of MAP2+ hippocampal neurons cells in both young and aging neuronal-HUCB co-cultures was significantly higher than in the control cultures (hippocampal mono-cultures). These MAP2+ neurons in co-culture were richly arborized, especially in 21 and 28 DIV co-cultures, and expressed functional enzymes (Synaptophysin, tyrosine hydryoxlase (TH)), gamma amino butyric acid receptor (GABAAr) and glutamate transporter (EAAC1). The majority of hippocampal neurons in both co-culture systems grew very well and survived for up to 42 DIV with an increment of immature neurons which were positive for Nestin and TuJ1. Using a multiplex protein array, a number of secreted proteins that could have trophic effects on the neurons were identified.


Darlington D.,University of South Florida | Deng J.,University of South Florida | Deng J.,Chongqing Medical University | Giunta B.,University of South Florida | And 9 more authors.
Stem Cells and Development | Year: 2013

Alzheimer's disease (AD) is the most common progressive age-related dementia in the elderly and the fourth major cause of disability and mortality in that population. The disease is pathologically characterized by deposition of β-amyloid plaques neurofibrillary tangles in the brain. Current strategies for the treatment of AD are symptomatic only. As such, they are less than efficacious in terms of significantly slowing or halting the underlying pathophysiological progression of the disease. Modulation by cell therapy may be new promising disease-modifying therapy. Recently, we showed reduction in amyloid-β (Aβ) levels/β-amyloid plaques and associated astrocytosis following low-dose infusions of mononuclear human umbilical cord blood cells (HUCBCs). Our current study extended our previous findings by examining cognition via (1) the rotarod test, (2) a 2-day version of the radial-arm water maze test, and (3) a subsequent observation in an open pool platform test to characterize the effects of monthly peripheral HUCBC infusion (1×106 cells/μL) into the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) from 6 to 12 months of age. We show that HUCBC therapy correlates with decreased (1) cognitive impairment, (2) Aβ levels/β-amyloid plaques, (3) amyloidogenic APP processing, and (4) reactive microgliosis after a treatment of 6 or 10 months. As such, this report lays the groundwork for an HUCBC therapy as potentially novel alternative to oppose AD at the disease-modifying level. © 2013, Mary Ann Liebert, Inc.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 422.95K | Year: 2013

DESCRIPTION (provided by applicant): Diabetes mellitus (DM) leads to a 3-4 fold higher risk of experiencing ischemic stroke. In addition, DM stroke patients are more prone to develop more and earlier white matter (WM) high-intensity lesions than non DM stroke patients. Treatment of stroke with tissue plasminogen activator (rtPA) at 2-3 hours after stroke decreases lesion volume in non-DM rats. However, tPA does not reduce lesion volume nor improve functional outcome, but increases the incidence of brain hemorrhage and blood-brain barrier (BBB) leakage in the ischemic brain of DM rats. In addition, treatment of stroke with bone marrow stromal cells (BMSCs) improves functional outcome in wild-type (WT)-stroke rats but not in DM-stroke rats. Therefore, effective therapy of stroke in the non-DM population may not necessarily transfer to the DM population, prompting the need to develop therapeutic approaches specifically designed to reduce neurological deficits after stroke in the DM population. Human umbilical cord blood cells (HUCBCs) are less mature than bone marrow and can be successfully used even when there is only a half-match. We found that treatment of stroke with HUCBCs starting at 1 or 3 days after middle cerebral artery occlusion (MCAo) improves recovery of neurological function in DM rats. In a novel and clinically relevant approach, based on our robust preliminary data, we therefore, propose to use HUCBCs for the treatment of stroke in the type two DM (T2DM) rats. The following specific aims and associated hypotheses will develop HUCBC as a safe and novel neurorestorative therapy which improves neurological function and reduces WM dysfunction and vascular damage in T2DM rats subjected to MCAo. In Aim 1 will investigate the safety and therapeutic effectof treatment of stroke in T2DM rats with HUCBCs. In addition, we will test the therapeutic effect of combination of HUCBC with tPA in T2DM rats; we will identify any potential adverse effects of tPA on HUCBCs and determine whether HUCBC treatment attenuates tPA induced adverse effects in T2DM rats. In Aim 2, we will elucidate the neurorestorative effect of HUCBC on WM remodeling after stroke in T2DM rats. HUCBCs have great commercialization potential as therapeutic agents, since they are readily available and easy to isolate without serious ethical and technical problems. HUCBCs can be used for autologous transplantation or allogeneic transplantation, when and if needed. The potential therapeutic impact of HUCBC on recovery on neurological function after stroke in the diabetic brain and the corresponding remodeling of the ischemic brain in DM rats opens enormous possibilities. This proposal is highly clinically relevant and if successful, will significantly impact the treatment of diabetic and possibly all stroke patients. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Diabetes mellitus (DM) is a severe health problem associated with both microvascular and macrovascular disease and leads to a 3-4 fold higher risk of experiencing ischemic stroke.Efficacious therapies for stroke in the non-DM population do not necessarily transfer to the DM population, prompting the need to develop therapeutic approaches specifically designed to reduce neurological deficits after stroke in the DM population. Our preliminary data show that human umbilical cord blood cell (HUCBC) treatment improves functional outcome after stroke in DM rats. Thus, we propose to develop HUCBC cell-based therapy as a neurorestorative treatment for stroke in the DM population.


Trademark
Saneron Ccel Therapeutics, Inc. | Date: 2012-12-14

umbilical cord blood. umbilical cord blood for medical applications.

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