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New York, NY, United States

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The disclosure provides cancer stem cells responsible for vascular mimicry, for use in stimulating immune response against a cancer. Methods for preparing and purifying the cancer stem cells are provided.


The present disclosure provides reagents and methods for stimulating an immune response against an antigen associated with glioblastoma multiforme.


Patent
NeoStem | Date: 2013-03-25

The invention provides a composition comprising enriched extracellular vesicles, wherein the extracellular vesicles express VSEL markers. The extracellular vesicles are used to treat or regenerate damages or injured tissue in a subject.


The disclosure provides cancer stem cells, for use in stimulating immune response against a cancer, such as colon carcinoma (CC). Methods for preparing and purifying the cancer stem cells are provided.


The disclosure provides cancer stem cells, for use in stimulating immune response against a cancer, such as ovarian carcinoma. Methods for preparing and purifying the cancer stem cells are provided.


The disclosure provides cancer stem cells, for use in stimulating immune response against a cancer, such as hepatocellular carcinoma (HCC). Methods for preparing and purifying the cancer stem cells are provided.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 147.76K | Year: 2013

DESCRIPTION (provided by applicant): Scleroderma is an autoimmune, connective tissue disorder which causes fibrosis of the skin and internal organs. In the skin, there is overproduction of extracellular matrix, and type 1 and 3 collagen. The disease involves vascular breakdown where the blood vessels in the skin degenerate and are replaced by collagen to form fibrotic tissue. The sclerotic tissue can also lead to digital ischemia and ulcers. Because of the vasculopathy, there is diminished blood supply to the lesion making the ulcers difficult to heal, prone to infection and progression to gangrene can occur that requires amputation. The ischemic ulcers are frequent, painful, and cause significant morbidity. There are 300,000 people in the US who have scleroderma. There is presently no effective treatment of scleroderma or the ischemic ulcers. Studies by our collaborator, Dr. Vincent Falanga, have shown that one approach that seems effective in healing chronic wounds is through the use of autologous bone marrow (BM) derived stem cells (BMSC). Animal studies showed the BMSCs could effectively heal wounded skin and facilitate production of new blood vessels, and keratinocytes. Autologous BMSCs were also found effective in treating non-healing human chronic wounds in clinical studies. These studies suggest that autologous stem cells in the BM may provide a useful cell based therapy to treat chronic wounds, including digital ischemic ulcers in scleroderma. Studies by NeoStem and its collaborators have shown that within the BM is a resident population of adult, pluripotent stem cells referred to as very small embryonic-like stem cells (VSEL). Animal studies have indicated the potential of VSELs in regenerative medicine by their ability to repair cardiac tissue aftermyocardial infarct and their ability to reconstitute te immune system after radiation exposure. Adult murine and human VSELs are expressed in BM but can be mobilized to migrate to peripheral blood following G-CSF stimulation where they can be isolated byapheresis and FACS. Consequently, VSELs have potential advantages over use of BMSC in treating chronic wounds because they can be collected in a less invasive manner. In this phase 1 SBIR grant, we propose test the efficacy of VSELs in treating difficultto heal wounds in an animal model of scleroderma the tight skin (Tsk) mouse to establish the potential utility of these cells in treating a debilitating consequences of this disease. The Tsk mouse carries a heterogeneous mutation for the fibrillin-1 gene and rapidly exhibits the characteristic tight and thickened skin phenotype of scleroderma patients. The mice express many symptoms of the scleroderma patient including increases in collagen content in skin as well as immune system dysfunction. The mice havebeen used extensively to test for potential efficacy of treatments for scleroderma and we propose to employ them to test the potential wound healing capabilities of autologous VSELs in treating difficult to heal skin ulcers in this disease. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Studies proposed in this grant will test the ability of adult, pluripotent VSELs to heal difficult skin wounds in an animal model of Scleroderma. If successful, these efficacy results would support the continued development of VSELs as a therapeutic to heal chronic dermal wounds. NeoStem would pursue the development of VSEL therapy with Dr. Falanga in future clinical studies on humans with difficult to heal wounds.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.22M | Year: 2012

DESCRIPTION (provided by applicant): Bone loss due to fractures and disease is a serious medical condition in the US affecting millions of Americans. It is particularly a problem with oral craniofacial disorders were the costs of treating damage exceeds60 billion annually. Furthermore, periodontitis is associated with systemic disorders such as diabetes mellitus, preterm low birth weight, and cardiovascular disease. While major efforts have been made to understand mechanisms of healing of large bones andto develop therapeutics to treat overall bone loss, very little information is available on bone remodeling in the human craniofacial skeleton, nor the mechanisms involved in osteonecrosis of the jaw and there are few effective treatments. The results ofour phase 1 SBIR showed that a unique population of human, adult, pluripotent, Very Small Embryonic like (VSEL) stem cells, have important bone regenerative properties and could be useful in treating oral-craniofacial disorders. Human VSELs are pluripotentstem cells involved in the normal turnover and regeneration of tissues and their circulating levels greatly increase in response to injury. They are able to repair injured tissues such as the heart after myocardial infarct. Adult human VSELs, are SSEA-4+/Oct-4+/CD133+/CXCR4+/Lin-/CD45-, express pluripotency markers (Oct-4 and Nanog) and are capable of differentiation into cells from all three germ lineages. With our collaborator, Dr. Russell Taichman of the University of Michigan we showed that VSELs differentiate to osteoblastic lineage after intra-marrow transplant. Importantly, VSELs from adult humans repaired a calvarial defect in SCID mice. The human VSELs formed new bone when applied in the injured area as measured by u-CT scan, and histological analysis demonstrated osteogeneis, significant new bone formation, dense thickening of the trabeculae and bone marrow formation. Most importantly, new bone tissue was derived from the human VSELs. These studies show that VSELs can generate new bone and have thepotential to repair bone injuries. In this phase 2 SBIR, we propose to further test the effectiveness of human VSELs to regenerate bone in human patients. Specifically, we will test the ability of VSELs to promote bone remodeling in the human craniofacialskeleton. For our studies, we will test the efficacy of human VSELs to generate bone in humans in a tooth extraction model in which individuals requiring tooth extraction due to caries or periodontal disease will be the subjects. In these individuals, theunderlying jaw bone tissue is injured and depleted and while there is some healing overtime after tooth extraction, the process is slow. We will test whether VSELs isolated from the patient expedite bone growth in the oral cavity after tooth removal. TheVSELs are autologous and will not cause rejection and do not form tumors or cause other health risks. This is not a clinical trial but a focused patient based study intended to move forward the development of VSELs as a therapeutic for bone repair. It successful, these studies will provide the basis for the rapid clinical development of VSELs for craniofacial osseous regeneration and treatment of a number of other skeletal based disorders. PUBLIC HEALTH RELEVANCE: It is a goal of NeoStem to develop the therapeutic capabilities of Human VSELs to treat a host of diseases and disorders. Studies in this proposal are focused on establishing the utility of VSELs to repair bone and treat oral-craniofacial disorders. If the results of these studies in humans show safety and efficacy of adult autologous VSELs in bone repair, then we will attempt to further develop this cell therapy in clinical studies in the futureto establish the cells as a standard of care for the treatment of bone disease and loss.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 595.25K | Year: 2012

DESCRIPTION (provided by applicant): In the event of a nuclear accident or terrorist bomb, large numbers of casualties will have been exposed to acute high-dose radiation. Those exposed will have compromised immune systems such that the virulence and infectivity of biological agents is dramatically increased. A compromised immune system exacerbates the effects of infectious agents and may preclude use of vaccines. Death can occur within 1-6 weeks following radiation exposure due to overwhelming infectionor to massive bleeding. The primary cause of death from radiation injury is infection that is unrestrained due to the failure of the immune system. There is only one intervention that saves a fatally irradiated person - a rescue through stem cell transplantation. The cure rate for this treatment can be high, provided the treatment is delivered within 7-10 days following exposure to radiation. Our goal is to develop very small embryonic like stem cells (VSEL), which are autologous adult pluripotent stem cells, as a countermeasure to radiological and nuclear threat. The VSELs will be used to rescue the immune system of individuals suffering from the delayed effects of acute radiation syndrome (ARS). The cells are autologous and consequently when administered to a patient will not cause rejection or graft- versus host disease, a common cause of failure of allogeneic stem cell therapies. The cells are pluripotent and can be expanded and differentiated to all three germ cell lineages. In particular, VSELs can be differentiated to hemato/lymphopoietic lineage, and can rescue the immune system of mice exposed to lethal radiation. Furthermore, VSELs have been shown to repair damaged tissue in animal models of myocardial infarct and may also be effective in repairing other tissues including retina and pancreas. Consequently, VSELs might be an ideal cell therapy to regenerate the body's immune system and repair other tissues damaged by radiation exposure. Most importantly, VSELs are resistant to lethal irradiation, whichdestroys hematopoietic stem cells and most other stem cells in the body. Specifically, in mice exposed to lethal radiation, VSELs are alive in bone marrow and proliferate in response to the tissue damage caused by irradiation. Consequently, these cells represent a unique population of autologous PSCs that could be used to treat radiation exposure. Studies proposed in this grant will test whether irradiated VSELs, can rescue the immune system and prolong survival of irradiated mice. If successful, this finding would indicate that VSELs could be isolated from a person exposed to radiation and used to treat that same person. Furthermore, we will test whether human VSELs have the same curative effect as the murine VSELs and are able to reverse the loss of the hemato/lymphopoietic system resulting from whole body irradiation. Importantly, unlike the development of medicinal products which must undergo extensive preclinical testing before human trials, VSELs are autologous and may be more readily available for human testing once preclinical efficacy is established. PUBLIC HEALTH RELEVANCE: NeoStem's goal is to develop a human VSEL product that can be used to recover the lost immune system resulting from radiation exposure. The product, which is an autologous stem cell therapy derived from the patient, could be used to rescue patients that have been exposed to radiation due to nuclear accident or terrorist threat. The product could also be used to treat cancer patients who have undergone radiation therapy andwho consequently have compromised immune systems.


Patent
NeoStem | Date: 2014-03-07

This application provides compositions for wound repair comprising VSEL stem cells and methods for treating acute and chronic cutaneous wounds, including burns and ulcers.

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