EP1192243A1 - Procede destine a promouvoir l'hematopoiese - Google Patents

Procede destine a promouvoir l'hematopoiese

Info

Publication number
EP1192243A1
EP1192243A1 EP00943131A EP00943131A EP1192243A1 EP 1192243 A1 EP1192243 A1 EP 1192243A1 EP 00943131 A EP00943131 A EP 00943131A EP 00943131 A EP00943131 A EP 00943131A EP 1192243 A1 EP1192243 A1 EP 1192243A1
Authority
EP
European Patent Office
Prior art keywords
hematopoiesis
vascular tissue
cells
subject
isolated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00943131A
Other languages
German (de)
English (en)
Other versions
EP1192243A4 (fr
Inventor
William H. Fleming
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Oregon Health Science University
Original Assignee
Oregon Health Science University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Oregon Health Science University filed Critical Oregon Health Science University
Publication of EP1192243A1 publication Critical patent/EP1192243A1/fr
Publication of EP1192243A4 publication Critical patent/EP1192243A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/44—Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells

Definitions

  • Agent that affects hematopoiesis A compound, antibody, nucleic acid molecule or protein that affects hematopoiesis.
  • the agent affects the growth, proliferation, maturation, or differentiation of hematopoietic cells.
  • An agent can be a naturally occurring molecule or a synthetic molecule.
  • the agent is a pharmaceutical compound.
  • the agent is a protein, such as a growth factor.
  • the agent is a nucleic acid molecule, such as an antisense or ribozyme molecule.
  • Supernatant The culture medium in which a cell is grown.
  • the culture medium includes material from the cell, including secreted growth factors.
  • the therapeutically effective portion of a vascular tissue will be dependent on the type of vascular tissue utilized (e.g. artery, vein or capillary), the subject being treated (e.g. the species or size of the subject), the degree that the subject is immunocompromised, and the location of the transplant (e.g. intraperitoneal, kidney capsule, etc).
  • the type of vascular tissue utilized e.g. artery, vein or capillary
  • the subject being treated e.g. the species or size of the subject
  • the degree that the subject is immunocompromised e.g. intraperitoneal, kidney capsule, etc.
  • Vascular Tissue Tissue consisting of, or containing, vessels as an essential part of a structure. vascular tissue operates by means of, or is made up of an arrangement of, vessels.
  • the subject can be an immunologically normal subject
  • the subject is immunocompromised (e g a phenotypcially or genetically immunocompromised subject)
  • the subject may be generally immunocompromised, so that the responses of all of the cells of the immune system are impaired, or the subject may be immunocompromised in one particular aspect of the immune response, such as the responsiveness of a specific cell type
  • T cell responses are impaired
  • B cell response is impaired
  • a monocyte or macrophage response is impaired
  • the liver then becomes the primary site of hematopoiesis during fetal development until late in gestation, when the medullary cavity of the bones is formed and seeded with hematopoietic precursors from the fetal liver.
  • the bone marrow has become the principal site of hematopoiesis and continues to produce blood cells throughout the lifetime of higher vertebrates.
  • This model is based on the orderly migration of hematopoietic precursors as determined primarily by morphologic studies of erythropoiesis during embryonic and fetal development. Modern transplantation studies however have revealed that hematopoietic stem cell development is more complex.
  • mice are phenotypically immunocompromised, such as by treatment with high doses of radiation, a marked depletion of hematopoietic progenitor cells and stem cells within the bone marrow is observed. This depletion of cells is accompanied by the production of a number of cytokines and growth factors that facilitate engraftment of transplanted donor hematopoietic cells (such as stem cells isolated from the bone marrow) into the irradiated hematopoietic microenvironment. It has previously been demonstrated that irradiated recipient mice will die within 3 weeks from bone marrow failure if they are not transplanted with a sufficient number of primitive donor hematopoietic cells.
  • Vascular tissue grafts give rise to colony forming cells in the spleen
  • Ly5.2 donor VC or TA grafts were implanted under the kidney capsule of irradiated Ly5.1 recipients. The percentage of Ly5.2 donor cells present in the peripheral blood was then evaluated (see Fig. 5). The results demonstrated that recipient cells could also participate in hematopoiesis. The results also demonstrate that the levels of donor cells decline over time. This indicates a very high degree of host recovery, and demonstrates a highly protective effect of components of the vascular graft on the host stem cells. This protective effect may be cytokine mediated. It should be noted that the use of higher doses of radiation can further compromise the host stem cells, and thus can ensure that donor cells predominate over time.
  • the experiments described above were performed using the largest blood vessels found in the murine circulatory system.
  • explants of normal ROSA26 adult heart and lung were transplanted into irradiated mice.
  • Any means of sampling the vascularized tissue can be utilized to sample differentiated tissues, including surgical removal or punch biopsy.
  • the tissue was dissected from donor animals, and a portion of the heart or lung (approximately 10 mg) was utilized.
  • Fourteen days after transplantation the recipients were sacrificed, and cross sections were prepared of the cardiac tissue or pulmonary tissue transplants.
  • ROSA26 donor mice are employed to demonstrate that these phenotypically defined cell populations are derived from the vascular graft donor and not a population of host cells that have subsequently migrated into the transplanted vascular tissue.
  • Immunoche istry provides tissue specific localization of phenotypically defined cells within the transplanted vascular graft. The primary limitation of this technique is that it is difficult to study the co-expression of more than 2 markers on an individual cell. To overcome this limitation, flow cytometry is used to examine the simultaneous expression of up to 4 cell surface markers on individual donor cells.
  • a first separation starting with at least about IX 10 10 to 3X 10 10 cells, antibodies are used for the various dedicated lineages (B cell, T cell, macrophage, etc.). These antibodies are each conjugated to different fluorochromes. Fluorochromes which may find use in a multi-color analysis include phycobiliproteins, e.g., phycoerythrin and allophycocyanins, fluorescein, Texas red, etc. While each of the lineages may be separated in a separate step, it is also possible to separate the lineages are separated at the same time. Generally, the number of cells obtained will be fewer than about 1% of the original cells, generally fewer than about 0.5% and may be as low as 0.2% or less. The cells can also be further separated by positively selecting for the expression of Thy
  • the particular order of separation is not critical
  • the cells are initially separated by a coarse separation, followed by a fine separation, negative selection for markers associated with lineage committed cells If positive selection of a marker associated with stem cells is utilized, it is performed at the same time as the negative selection, or following negative selection This separation is followed by an assay to determine if the cellular composition has multi-lineage potential and enhanced self-regeneration capability
  • a factor that protects normal stem cells from lethal irradiation may have a variety of clinical applications (e.g. to rescue the marrow of humans exposed to lethal irradiation, or to treat pateints with hematologic malignancies, such as by protecting normal stem cells while abnormal cells are removed).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Veterinary Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biotechnology (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Food Science & Technology (AREA)
  • Diabetes (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Microbiology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un procédé destiné à promouvoir l'hématopoïèse et consistant à transplanter, sur un sujet, au moins une portion efficace sur le plan thérapeutique d'un tissu vasculaire isolé, de manière que ce tissu vasculaire favorise l'hématopoïèse; elle concerne également un procédé de détection d'un agent agissant sur l'hématopoïèse, consistant à transplanter sur un sujet une portion d'un tissu vasculaire isolé, de manière que cette portion de tissu soit suffisante pour promouvoir l'hématopoïèse. On traite le tissu vasculaire à l'aide d'un agent, on détecte l'hématopoïèse chez le sujet, et on compare cette hématopoïèse avec celle d'un témoin, un changement dans l'hématopoïèse du sujet par rapport au témoin indiquant que l'agent agit sur l'hématopoïèse. L'invention concerne encore une technique d'isolation d'un facteur de croissance hématopoïétique, ainsi qu'une technique d'isolation d'une cellule souche hématopoïétique, dans lesquelles on utilise le procédé de l'invention. L'invention concerne en outre des compositions pharmaceutiques et des trousses destinées à promouvoir l'hématopoïèse, ainsi qu'un modèle animal non humain servant à l'essai des agents agissant sur l'hématopoïèse. Ce modèle est un animal non humain présentant une carence de type hématopoïétique et sur lequel on a transplanté une portion isolée d'un tissu vasculaire, suffisante pour promouvoir l'hématopoïèse.
EP00943131A 1999-06-23 2000-06-22 Procede destine a promouvoir l'hematopoiese Withdrawn EP1192243A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US14062899P 1999-06-23 1999-06-23
US140628P 1999-06-23
PCT/US2000/017427 WO2000078930A1 (fr) 1999-06-23 2000-06-22 Procede destine a promouvoir l'hematopoiese

Publications (2)

Publication Number Publication Date
EP1192243A1 true EP1192243A1 (fr) 2002-04-03
EP1192243A4 EP1192243A4 (fr) 2003-05-28

Family

ID=22492106

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00943131A Withdrawn EP1192243A4 (fr) 1999-06-23 2000-06-22 Procede destine a promouvoir l'hematopoiese

Country Status (5)

Country Link
EP (1) EP1192243A4 (fr)
JP (1) JP2003530899A (fr)
AU (1) AU780468B2 (fr)
CA (1) CA2375527A1 (fr)
WO (1) WO2000078930A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050208025A1 (en) * 2002-04-16 2005-09-22 Fleming William H Enhancement of hematopoietic stem cell survival
US9216219B2 (en) 2012-06-12 2015-12-22 Novartis Ag Anti-BAFFR antibody formulation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0730849A2 (fr) * 1995-03-09 1996-09-11 University Of Bristol Greffe artérioveineuse à bypass
US5637323A (en) * 1994-11-16 1997-06-10 The United States Of America As Represented By The Department Of Health And Human Services Method of mobilizing pluripotential hematopoietic stem cells with IL-7
WO1997022708A1 (fr) * 1995-12-19 1997-06-26 Systemix, Inc. Cellules souches hematopoietiques embryonnaires de primate, formant des groupements
US5643741A (en) * 1990-03-30 1997-07-01 Systemix, Inc. Identification and isolation of human hematopoietic stem cells
WO1998012304A1 (fr) * 1996-09-19 1998-03-26 Medical Research Council Systeme de mise en culture de cellules souches hematopoietiques

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE397769B (sv) * 1974-11-04 1977-11-21 Gambro Ab Insatselement till anvendning vid kerlkirurgi samt sett att framstella dylikt
GB9526423D0 (en) * 1995-12-22 1996-02-21 Koopmans Sietse Beheer Bv Wellhead apparatus

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5643741A (en) * 1990-03-30 1997-07-01 Systemix, Inc. Identification and isolation of human hematopoietic stem cells
US5637323A (en) * 1994-11-16 1997-06-10 The United States Of America As Represented By The Department Of Health And Human Services Method of mobilizing pluripotential hematopoietic stem cells with IL-7
EP0730849A2 (fr) * 1995-03-09 1996-09-11 University Of Bristol Greffe artérioveineuse à bypass
WO1997022708A1 (fr) * 1995-12-19 1997-06-26 Systemix, Inc. Cellules souches hematopoietiques embryonnaires de primate, formant des groupements
WO1998012304A1 (fr) * 1996-09-19 1998-03-26 Medical Research Council Systeme de mise en culture de cellules souches hematopoietiques

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GRIMEE RENEE ET AL: "Acute stress in rats produces a rapid and sustained increase in prostacyclin production in aortic tissue: Dependence on corticosterone." LIFE SCIENCES, vol. 57, no. 1, 1995, pages 69-81, XP002236305 ISSN: 0024-3205 *
LAMM P; ET AL: "NEW ALTERNATIVE CORONARY BYPASS GRAFT: FIRST CLINICAL EXPERIENCE WITH AN AUTOLOGOUS ENDOTHELIALIZED CRYOPRESERVED ALLOGRAFT" CIRCULATION, vol. 117, no. 6, 1999, pages 1217-1219, XP009005643 *
OHLSTEIN ELIOT H ET AL: "SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 91, no. 17, 1994, pages 8052-8056, XP002236306 1994 ISSN: 0027-8424 *
See also references of WO0078930A1 *

Also Published As

Publication number Publication date
WO2000078930A1 (fr) 2000-12-28
AU780468B2 (en) 2005-03-24
AU5764700A (en) 2001-01-09
CA2375527A1 (fr) 2000-12-28
JP2003530899A (ja) 2003-10-21
EP1192243A4 (fr) 2003-05-28

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