METASTATIC CANCER DECOY TRAP

A method of treating or preventing cancer metastasis in a subject is described. The method includes implanting a decoy trap within the subject, the decoy trap comprising an implantable trap device including a metastatic cancer attractant. Methods of diagnosing cancer metastasis in a subject using the decoy traps are also described. The methods include implanting the decoy trap in the subject and allowing the decoy trap to remain within the subject for a period of time, and then diagnosing the subject as having metastatic cancer if metastatic cancer cells are detected in the decoy trap. 1. A method of treating or preventing cancer metastasis in a subject , comprising implanting a decoy trap within the subject , the decoy trap comprising an implantable trap device including a metastatic cancer attractant.2. The method of claim 1 , wherein the cancer metastasis is bone metastasis claim 1 , and the metastatic cancer attractant is a bone-seeking cancer attractant.3. The method of claim 2 , wherein the bone-seeking cancer attractant is pericytes.4. The method of claim 3 , wherein the subject is human and the pericytes are human pericytes.5. The method of claim 2 , wherein the implantable trap device comprises bone tissue.6. The method of claim 2 , wherein the implantable trap device comprises a porous calcium phosphate ceramic.7. The method of claim 1 , wherein the method is used to treat the metastasis originating from breast cancer claim 1 , prostate cancer claim 1 , or lung cancer primary tumors.8. The method of claim 1 , wherein the decoy trap comprises a composite vascular structure.9. The method of claim 1 , wherein the decoy trap further comprises a labeled probe that specifically binds to cancer cells.10. The method of claim 1 , wherein the decoy trap is implanted in contact with a blood vessel.11. A method of diagnosing cancer metastasis in a subject claim 1 , comprising implanting a decoy trap within the subject claim 1 , the decoy trap comprising an implantable ...

MESENCHYMAL STEM CELL COMPOSITIONS FOR THE TREATMENT OF MICROBIAL INFECTIONS

A method of treating a microbial infection in a subject includes administering to the subject a therapeutically effective amount of MSCs and an antimicrobial agent, wherein the MSCs potentiate the therapeutic activity of the antimicrobial agent, and the therapeutically effective amount is the amount effective to inhibit microbial growth and suppress microbial infection associated inflammation in the subject. 1. A method of treating a microbial infection in a subject comprising administering to the subject a therapeutically effective amount of MSCs , wherein the therapeutically effective amount is the amount effective to inhibit microbial growth and suppress microbial infection associated inflammation in the subject.2. The method of claim 1 , wherein the MSCs are provided in a pharmaceutical composition with a pharmaceutically acceptable carrier and administered to the subject via intramuscular claim 1 , inhalation claim 1 , intravenous or retro-orbital administration.3. The method of claim 1 , wherein the MSCs are allogeneic or autologous MSCs.4. The method of claim 1 , the MSCs comprising preconditioned MSCs claim 1 , wherein the preconditioned MSCs are cultured in a microbial infection associated disease setting prior to administration of the MSCs to the subject.5. The method of claim 4 , the disease setting comprising one or more inflammatory cytokines related to a microbial infection.7. The method of claim 5 , the inflammatory cytokines selected from the group consisting of TNFα claim 5 , IFNγ claim 5 , IL-1β claim 5 , IL-6 claim 5 , IL-10 claim 5 , IL-17 and MIP-1α.8Pseudomonas aeruginosa, Staphylococcus aureusStreptococcus pneumoniae. The method of claim 1 , wherein the microbial infection is a respiratory microbial infection associated with cystic fibrosis claim 1 , the microbial infection selected from the group consisting of claim 1 , and microbial infection.9. A method of treating a microbial infection in a subject comprising administering to the subject a ...

ISOLATING AND THERAPEUTIC USE OF PERIVASCULAR MEDICINAL CELLS

Disclosed are perivascular medicinal cells (PVMCs), methods of isolating PVMCs, and a composition comprising PVMCs having medicinal capabilities. Specifically, the disclosure provides a method of isolating PVMCs from an umbilical cord blood vessel or from bone. The disclosure further provides a method of making an enhanced, autologous bone graft, a method of stimulating bone regeneration comprising administering a therapeutically effective amount of bone-derived PVMCs, a method of reconstructing bone tissue, and methods of treating a disease that affects cellular function. PVMCs capable of secreting a site-dependent trophic factor are also described. 174.-. (canceled)75. A composition comprising pure , substantially pure , or impure isolated PVMCs , wherein the PVMCs have medicinal capabilities.76. The composition of claim 75 , wherein the isolated PVMCs may be capable of expressing CD146 claim 75 , CD105 claim 75 , CD166 claim 75 , CD44 claim 75 , CD73 claim 75 , CD90 claim 75 , or a combination thereof.77. The composition of claim 75 , wherein the isolated PVMCs are isolated from bone.78. The composition of claim 77 , wherein bone comprises a bone chip claim 77 , a trabecular bone cavity claim 77 , bone marrow claim 77 , bone cavity lavage claim 77 , or a combination thereof.79. The composition of claim 75 , wherein the medicinal capabilities of the isolated PVMC are defined by the spectrum of molecules secreted by the PVMC.80. The composition of claim 79 , wherein the spectrum of molecules secreted by the isolated PVMC is site dependent.81. The method of claim 75 , wherein the pure claim 75 , substantially pure or impure isolated PVMCs further comprise bone chips claim 75 , fully demineralized bone chips claim 75 , or partially demineralized bone chips.82. A method for isolating PVMCs from bone the method comprising: (i) providing a sample of bone tissue from a subject; (ii) extracting the PVMCs from the bone; and (iii) concentrating the extracted PVMCs.83. The ...

PERICYTE ASSAY FOR TRANSENDOTHELIAL MIGRATION

A test animal for identifying blood vessel transendothelial migration-affecting factors or agents is described. The test animal comprises an implanted tissue mimicking model with a composite vascular structure comprising pericytes on test animal vasculature. The test animal can be used in a method of identifying or evaluating a blood vessel transendothelial migration-affecting agent that includes administering the agent to a test animal and determining the effect of the agent on the level of blood vessel transendothelial migration into or out of the tissue model. The test animal can also be used in a method of identifying or characterizing a metastasis-facilitating factor that includes administering or inducing circulating tumor cells in a test animal in which one or more factors in the pericyte have been silenced, and determining if the level of tumor cell migration into the tissue model has increased or decreased. 1. A method of identifying or evaluating a blood vessel transendothelial migration-affecting agent , comprising administering the agent to a test animal comprising an implanted tissue mimicking model with a composite vascular structure comprising donor pericytes on test animal vasculature , and determining the effect of the agent on the level of blood vessel transendothelial migration into or out of the tissue model.2. The method of claim 1 , wherein the blood vessel transendothelial migration is the facilitated transport of circulating cancer cells claim 1 , and the blood vessel transendothelial migration-affecting agent is an antimetastatic agent.3. The method of claim 1 , wherein the tissue mimicking model is a bone tissue model.4. The method of claim 1 , wherein the tissue mimicking model comprises a porous calcium phosphate ceramic cube.5. The method of claim 3 , wherein the blood vessel transendothelial migration is the facilitated extravasation of circulating melanoma cancer cells into the bone tissue model.6. The method of claim 1 , wherein the ...

COMPOSITIONS AND METHODS FOR TREATING LUNG REMODELING DISEASES

In one aspect, the present disclosure can relate to a method for treating a lung remodeling disease in a subject. One step of the method can include assaying one or more mesenchymal stem cells (MSCs) for one or more of the following effects: (1) reduce collagen deposition in the lungs of the subject; (2) increase expression of a transcription factor in an alveolar macrophage of the subject; (3) decrease expression of a cytokine in an alveolar macrophage of the subject; (4) decrease expression of a toll-like receptor (TLR) in an alveolar macrophage of the subject; (5) decrease mRNA synthesis of collagen 1 and/or collagen 3 in the subject; and (6) decrease the level of hyaluronic acid in the subject. A therapeutically effective amount of the one or more assayed MSCs found to have one or more of effects (1)-(6) can then be administered to the subject. 1. A method for treating a lung remodeling disease in a subject , the method comprising the steps of:assaying one or more mesenchymal stem cells (MSCs) for one or more of the following effects: (1) reduce collagen deposition in the lungs of the subject; (2) increase expression of a transcription factor in an alveolar macrophage of the subject; (3) decrease expression of a cytokine in an alveolar macrophage of the subject; (4) decrease expression of a toll-like receptor (TLR) in an alveolar macrophage of the subject; (5) decrease mRNA synthesis of collagen 1 and/or collagen 3 in the subject; (6) decrease the level of hyaluronic acid in the subject; (7) decrease the number of macrophages in lung tissue of the subject; (8) decrease the number of eosinophils in lung tissue of the subject; (9) decrease the number of polymorphonuclear leukocytes (PMNs) in lung tissue of the subject; (10) decrease systemic levels of an antibody in the subject; (11) decrease weight loss in the subject; and (12) decrease epithelial cell hyperplasia in the subject; andadministering to the subject a therapeutically effective amount of the one or ...

Human mesenchymal stem cells

Isolated human mesenchymal stem cells which can differentiate into more than one tissue type (e.g. bone, cartilage, muscle or marrow stroma), a method for isolating, purifying, and culturally expanding human mesenchymal stem cells (i.e. "mesenchymal stem cells" or "hMSCs"), and characterization of and uses, particularly research reagent, diagnostic and therapeutic uses for such cells. The stem cells can be culture expanded without differentiating. Monoclonal antibodies specific for human mesenchymal stem cells and the monoclonal hybridoma cell lines (ATCC nos. 10743-10745) that synthesize and secrete these monospecific antibodies, and uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Biomatrix for soft tissue regeneration using mesenchymal stem cells

An implant for repair of a tissue defect comprises a plurality of physiologically compatible load-bearing sutures for securing under tension tissue adjacent to the defect to be repaired, the sutures for supporting a tissue reparative cell mass in the defect and a tissue reparative cell mass supported thereby. The sutures have a central portion encapsulated in a cell containing matrix which is contracted under a tensile load by the cells thereof and formed into a mat sheet during the contraction. Spring metal wires hold the sutures in tension during the contraction. The matrix is a collagen gel or other material which the cells contract, the cells comprising human mesenchymal stem cells. The mat sheet is then rolled into a spiral roll with the sutures extending from opposite roll ends to form the desired implant. Different embodiments are disclosed.

Osteoarthritis cartilage regeneration

For repair of cartilage damaged as part of the degenerative effects of osteoarthritis, the inventors have found that the human mesenchymal stem cell approach makes it possible to: (1) regenerate both shallow cartilage chondral defects and full thickness cartilage defects (osteochondral lesions); (2) broaden the suitable clinical population to routinely include middle-aged patients; (3) eliminate the use of autologous tissue grafts (mature cartilage and the periosteal covering) to repair an articular cartilage injury; (4) regenerate other types of injured cartilage such as patellar and spinal disk cartilage; (5) regenerate articular joint cartilage in older patients with osteoarthritis; and (6) form new cartilage and subchondral bone which fully integrate into the adjacent normal tissue.

Method for enhancing the implantation and differentiation of marrow-derived mesenchymal cells

The present invention is directed to a method and device for enhancing the implantation and differentiation of marrow-derived mesenchymal cells (i.e. mesenchymal stem cells). The method and device of the invention are an effective means for treating skeletal and other connective tissue disorders.

Method for treating connective tissue disorders

The present invention is directed to various processes and devices for utilizing isolated and culturally expanded marrow-derived mesenchymal cells (i.e. mesenchymal stem cells) for treating skeletal and other connective tissue disorders.

Enhancing bone marrow engraftment using MSCS

Method and preparations for enhancing bone marrow engraftment in an individual by administering (i) a culturally expanded mesenchymal stem cell preparation and (ii) a bone marrow graft. The mesenchymal stem cells are administered in an mount effective to promote engraftment of the bone marrow.

Connective tissue regeneration using human mesenchymal stem cell preparations

Isolated human mesenchymal stem cells, a method for isolating, purifying, and culturally expanding human mesenchymal stem cells (i.e. mesenchymal stem cells or "MSCs"), and characterization of (including by cytokine expression profiling) and uses, particularly research reagent, diagnostic and therapeutic uses for such cells. The stem cells can be culture expanded without differentiating. Monoclonal antibodies specific for human mesenchymal stem cells and the monoclonal hybridoma cell lines (ATCC nos. 10743-10745) that synthesize and secrete these monospecific antibodies, and uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Monoclonal antibodies for human mesenchymal stem cells

The invention relates to isolated human mesenchymal stem cells, a method for isolating, purifying, and culturally expanding human mesenchymal stem cells (i.e. mesenchymal stem cells or "MSCs"), and characterization of (including by cytokine expression profiling) and uses, particularly research reagent, diagnostic and therapeutic uses for such cells. The stem cells can be culture expanded without differentiating. Further disclosed are monoclonal antibodies specific for human mesenchymal stem cells and the monoclonal hybridoma cell lines (ATCC nos. 10743-10745) that synthesize and secrete these monospecific antibodies, and uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Bone regeneration in osteoporosis using human bone marrow mesenchymal cells

The method of osteoporosis treatment and infusion compositions of the invention increase the number of the patient's own progenitor cells (hMSCs) and the reservoir of available bone-forming osteoblasts. They can be used to generate cortical and cancellous bone which has been lost as a result of post-menopausal osteoporosis, male idiopathic osteoporosis, congenital osteoporosis and other bone resorption diseases. Most cases of osteoporosis can be treated with a metered intravenous infusion of the composition of the invention over the course of 15-30 minutes, using customary cell reinfusion therapy techniques.

Cell targeting methods and compositions

In certain aspects, the invention relates to cell delivery compositions comprising a chondrogenic cell and a targeting moiety. Such compositions may be used, for example, in administering a targeted cell therapy to a subject.

Skin regeneration using mesenchymal stem cells

Disclosed is a multilayer skin equivalent having (i) a scaffold layer incorporated with dermis-forming cells, and (ii) a keratinocyte layer. Also disclosed is a multilayer dermal equivalent having at least one of (i) a first layer of at least one skin-associated extracellular matrix component containing papillary dermal fibroblasts; and, in laminar relationship therewith, (ii) a second layer of at least one skin-associated extracellular matrix component containing reticular dermal fibroblasts. Preferred embodiments include those where the scaffold or dermis-forming layer is a multilayer selected from the group consisting of (a) a layer containing isolated papillary dermis-forming cells and a layer containing isolated reticular dermis-forming cells; (b) a layer containing isolated papillary dermis-forming cells and a layer containing isolated, culture expanded mesenchymal stem cells; and (c) a layer containing isolated reticular dermisforming cells and a layer containing isolated, culture expanded mesenchymal stem cells. Also enclosed is a multilayer skin equivalent having (i) a scaffold layer comprising a first layer of at least one skin-associated extracellular matrix component containing papillary dermal fibroblasts and, in laminar relationship therewith, a second layer of at least one skin-associated extracellular matrix component containing reticular dermal fibroblasts; and (ii) a keratinocyte layer. Also disclosed is an injectable composition of dermis-forming cells and at least one skin-associated extracellular matrix component in a pharmaceutically acceptable injectable carrier. The injectable composition can further include keratinocytes.

Lineage-directed induction of human mesenchymal stem cell differentiation

Methods for in vitro or ex vivo lineage directed induction of isolated, culture expanded human mesenchymal stem cells comprising contacting the mesenchymal stem cells with a bioactive factor effective to induce differentiation thereof into a lineage of choice as well as such compositions including isolated culture expanded human mesenchymal stem cells and bioactive factors effective to induce directed lineage induction are disclosed. Further disclosed is this method which also includes introducing such culturally expanded lineage-induced mesenchymal stem cells into a host from which they have originated for purposes of mesenchymal tissue regeneration or repair.

Cell targeting methods and compositions

In certain aspects, the invention relates to cell delivery compositions comprising a progenitor cell and a targeting moiety, and methods related thereto. Such compositions and methods may be used, for example, in administering a targeted cell therapy to a subject.

Monoclonal antibodies for human osteogenic cell surface antigens

Monoclonal antibodies specific for normal human osteogenic cell subsets and the monoclonal hybridoma cell lines that synthesize and secrete these monospecific antibodies, as well as the uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Lineage-directed induction of human mesenchymal stem cell differentiation

Methods for in vitro or ex vivo lineage directed induction of isolated, culture expanded human mesenchymal stem cells comprising contacting the mesenchymal stem cells with a bioactive factor effective to induce differentiation thereof into a lineage of choice as well as such compositions including isolated culture expanded human mesenchymal stem cells and bioactive factors effective to induce directed lineage induction are disclosed. Further disclosed is this method which also includes introducing such culturally expanded lineage-induced mesenchymal stem cells into a host from which they have originated for purposes of mesenchymal tissue regeneration or repair.

Bone protein purification process

A process of extracting and purifying a bone protein capable of stimulating chondrogenic expression in undifferentiated cells in culture. The purification process is monitored at various stages by bioassaying the bone protein for chondrogenic activity in embryonic limb bud mesenchymal cell cultures.

Bone protein purification process

Monoclonal antibodies for human osteogenic cell surface antigens

Monoclonal antibodies specific for normal human osteogenic cell subsets and the monoclonal hybridoma cell lines that synthesize and secrete these monospecific antibodies, as well as the uses of the monoclonal antibodies for diagnostic and/or therapeutic purposes.

Skin regeneration using mesenchymal stem cells

Monoclonal antibodies specific for marrow-derived mesenchymal cells

Lineage-directed induction of human mesenchymal stem cell differentiation

BIOMATRIZ FOR THE REGENERATION OF FABRICS.

LA INVENCION SE REFIERE A UN IMPLANTE (1) PARA REPARAR UN DEFECTO DE UN TEJIDO, EL IMPLANTE (1) COMPRENDE UN MATERIAL EN FORMA DE HEBRA O SUTURA (2) Y UNA MATRIZ DE GEL (4) QUE CONTIENE CELULAS REPARADORAS (6) QUE SE HAN DISPUESTO ALREDEDOR DE UNA PARTE CENTRAL (8) DE LA SUTURA (2). LA SUTURA (2) TIENE EXTREMOS LIBRES (10 Y 12) QUE SE UTILIZAN PARA VOLVER A UNIR EL TEJIDO ADYACENTE AL DEFECTO. LOS EXTREMOS LIBRES (10 Y 12) PUEDE COSERSE DENTRO DEL CUERPO DEL TEJIDO SUJETANDO DE ESTA FORMA LOS EXTREMOS DEL TENDON EN SU SITIO Y SUJETANDO TAMBIEN LA MATRIZ DE GEL (4) EN LA POSICION DEL DEFECTO. THE INVENTION REFERS TO AN IMPLANT (1) TO REPAIR A DEFECT OF A FABRIC, THE IMPLANT (1) INCLUDES A MATERIAL IN THE FORM OF A THREAT OR SUTURE (2) AND A GEL MATRIX (4) CONTAINING REPAIR CELLS (6) THAT HAVE BEEN AROUND A CENTRAL PART (8) OF THE SUTURE (2). THE SUTURE (2) HAS FREE EXTREMES (10 AND 12) THAT ARE USED TO BIND THE ADJECTIVE FABRIC TO THE DEFECT. THE FREE EXTREME (10 AND 12) CAN BE SEWED WITHIN THE BODY OF THE FABRIC, SUBJECTING THE EXTREME TENDED IN THEIR SITE AND SUBJECTING THE GEL MATRIX (4) IN THE POSITION OF THE DEFECT.

Skin regeneration using mesenchymal stem cells

Cell targeting methods and compositions

Methods for generating cartilage tissue

A hyaline-like, single layer cartilage tissue construct includes chondrogenic cells dispersed within an endogenously produced extracellular matrix. The single layer cartilage tissue construct has a glycosaminoglycan content substantially equal to the glycosaminoglycan content of native cartilage tissue. A method for generating a single layer cartilage tissue construct includes isolating a population of chondrogenic cells and then expanding the population of chondrogenic cells. Next, the population of chondrogenic cells is seeded into a bioreactor having a volume defined by oppositely disposed gas permeable membranes. The population of chondrogenic cells is then cultured in a serum- free culture medium for a time sufficient to permit the population of chondrogenic cells to differentiate and form the single layer cartilage tissue construct.

Biomatrix für geweberegenaration

Procedimento di trattamento di cellule con proteine ossee solubili per renderle idonee a stimolare la crescita di tessuti cartilaginei ed ossei,e prodotto ottenuto

Menschliche mesenchym-stammzellen aus dem mark und monoklonale antikörper spezifisch gegen diese zellen

Zellinien-gerichtete induktion der menschlichen mesenchymalen stammzelldifferenzierung

Procedimento di purificazione di proteine ossee

Process of and material for stimulating growth of cartilage and bony tissue at anatomical sites