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Multipotent Adult Stem Cells And Uses of Multipotent Adult Stem Cells To Treat Inflammation

Inactive Publication Date: 2010-07-08
MESOBLAST INT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]In accordance with the present technology, multipotent adult stem cells can be used, for example, to treat an autoimmune disease, treat an inflammatory response, treat an allergic disease, treat a pulmonary disease having fibrotic and / or inflammatory components, repair epithelial damage, and promote wound healing in subjects, including a human subject. Autoimmune diseases that can be treated with multipotent adult stem cells include, for example, Type 1 Diabetes, inflammatory bowel disease, Crohn's disease, and uveitis. Pulmonary diseases that can be treated with multipotent adult stem cells include, but are not limited to, Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and asthma. Inflammatory responses, including those associated with autoimmune diseases or pulmonary diseases, can be reduced with multipotent adult stem cells. An inflammatory response can be reduced by, for example, reducing the production or expression of pro-inflammatory mediators, increasing the production or expression of anti-inflammatory mediators, or a combination thereof.
[0009]The present technology provides one or more cell preparations comprising adult bone marrow-derived stem cells in one or more doses effective to treat an inflammatory response in a subject. The subject can be a human having, for example, inflammatory bowel disease. The stem cells can be capable of differentiating into at least one cell type of each of the endodermal, ectodermal, and mesodermal embryonic lineages. The effective dose of the cell preparation can contain a sufficient number of stem cells to provide about 1×105 to about 1×107 cells per kilogram of the subject. In certain embodiments, the subject can be a mammal. The mammal can be, for example, a primate, including a human and a non-human primate. Administration of the cell preparation can, for example, elevate interferon-beta levels in the subject.
[0016]Furthermore, it is believed that multipotent adult stem cells stimulate dendritic cells (DCs) to produce Interferon-Beta (IFN-β), which promotes tumor suppression and immunity against viral infection.

Problems solved by technology

These immunological properties of MSCs can enhance their transplant engraftment and limit the ability of the recipient's immune system to recognize and reject allogeneic cells following transplantation.

Method used

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Examples

Experimental program
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Effect test

example 1

[0106]Materials and Methods Culture of human MSCs. Human MSCs were cultured as described by Pittenger et al., Science, Vol. 284, pg. 143 (1999). Briefly, marrow samples were collected from the iliac crest of anonymous donors following informed consent by Poietics Technologies, Div of Cambrex Biosciences. MSCs were cultured in complete Dulbecco's Modified Eagle's Medium-Low Glucose (Life Technologies, Carlsbad, Calif.) containing 1% antibiotic-antimyotic solution (Invitrogen, Carlsbad, Calif.) and 10% fetal bovine serum (FBS, JRH BioSciences, Lenexa, Kans.). MSCs grew as an adherent monolayer and were detached with trypsin / EDTA (0.05% trypsin at 37° C. for 3 minutes). All MSCs used were previously characterized for multilineage potential and retained the capacity to differentiate into mesenchymal lineages (chondrocytic, adipogenic, and osteogenic) (Pittenger, et al., Science, Vol. 284, pg. 143 (1999)).

[0107]Isolation of Dendritic cells. Peripheral blood mononuclear cells (PBMCs) were...

example 2

[0125]Mesenchymal stem cells were given to a 33-year-old female patient suffering from severe Grade IV gastrointestinal graft-versus-host disease (GVHD). The patient was refractory to all other GVHD treatments. Endoscopic views of the patient's colon showed areas of ulceration and inflammation prior to treatment. Histology of the patient's colon showed that the graft-versus-host disease had destroyed the vast majority of the patient's intestinal crypts, prior to treatment.

[0126]The patient was given an intravenous infusion of allogeneic mesenchymal stem cells in 50 ml of Plasma Lyte A (Baxter) in an amount of 3×106 cells per kilogram of body weight.

[0127]The patient was evaluated at two weeks post-infusion. At two weeks post-infusion, an endoscopic view of the patient's colon showed that the areas of inflammation and ulceration visible prior to treatment were resolved. In addition, a biopsy of the patient's colon showed significant regeneration of intestinal crypts. Thus, the admini...

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Abstract

Disclosed are cell preparations comprising multipotent adult stem cells and methods for using multipotent adult stem cells to treat autoimmune diseases, treat allergic responses, treat cancer, treat inflammatory diseases, treat fibrotic disorders, reduce inflammation and / or fibrosis, promote would healing, repair epithelial damage, and / or promote angiogenesis.

Description

RELATED APPLICATIONS[0001]This application is a continuation of application Ser. No. 11 / 541,853, filed Oct. 2, 2006, which is a continuation-in-part of application Ser. No. 11 / 080,298, filed Mar. 15, 2005, which claims priority based on provisional application Ser. No. 60 / 555,118, filed Mar. 22, 2004; the contents of each application are hereby incorporated by reference in their entireties.FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]The present technology was made with Government support under Contract No. N66001-02-C-8068 awarded by the Department of the Navy. The Government has certain rights in this technologyBACKGROUND OF THE INVENTION[0003]Mesenchymal stem cells (MSCs), which are present in adult bone marrow, are a kind of multipotent stem cell that can differentiate readily into lineages including osteoblasts, myocytes, chondrocytes, and adipocytes. (Pittenger, et al., Science, Vol. 284, pg. 143 (1999); Haynesworth, et al., Bone, Vol. 13, pg. 69 (1992); Prockop, Science, ...

Claims

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Application Information

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IPC IPC(8): A61K35/12A61P35/00A61P17/02A61K35/14A61K35/28C12N5/00C12N5/0775H04Q7/20
CPCA61K35/28C12N5/0663A61K38/2066A61K2035/124A61K38/2026C12N5/0675C12N5/0662C12N5/0664C12N5/0665C12N5/0666C12N5/0667C12N5/0668A61P1/00A61P1/02A61P1/04A61P11/00A61P13/08A61P17/00A61P17/02A61P17/06A61P17/14A61P19/02A61P19/08A61P25/00A61P27/02A61P29/00A61P35/00A61P37/00A61P37/02A61P37/06A61P37/08A61P43/00A61P5/14A61P7/04A61P7/06A61P9/00A61P3/10Y02A50/30A61K35/12A61K45/06
Inventor PITTENGER, MARK F.AGGARWAL, SUDEEPTA
Owner MESOBLAST INT
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