Compositions, methods, and devices for treating disease

• US 10,363,276 B2
• Filed: 12/11/2015
• Issued: 07/30/2019
• Est. Priority Date: 10/11/2006
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Yarmush, Martin Leon, Parekkadan, Biju
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US14/967,028
• Publication Number:
  US 20160331784A1
• Time in Patent Office: 1,327 Days
• Field of Search: None
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3689 by biological cells
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C12M 29/16 Hollow fibers hollow fiber modules in general B01D63/02
• CPC Class Codes: C12N 2502/1358 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/067 Hepatocytes
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 2800/085 Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
• CPC Class Codes: G01N 33/5067 Liver cells
• CPC Class Codes: G01N 33/5073 Stem cells

Abstract

Described are compositions and methods for treating liver disease, e.g., acute liver disease, using bone marrow-derived stem cells and bone marrow-derived stem cell conditioned media.

Claims

1. A method of preparing a composition for the treatment of liver disease, the method comprising:

(i) obtaining a population of undifferentiated multipotent stromal cells (MSCs);

(ii) culturing the MSCs in a medium;

(iii) obtaining the medium resulting from the culturing of (ii);

(iv) fractionating the medium obtained in (iii);

(v) selecting a fraction of the medium that is capable of one or both of promoting hepatocyte proliferation or inhibiting hepatocyte death; and

(vi) formulating the selected fraction to form a composition for administration to a mammal.

2. The method of claim 1, wherein the composition is concentrated 25-fold.

3. The method of claim 2, wherein the medium comprises a serum free tissue culture medium.

4. The method of claim 1, further comprising lyophilizing the composition.

5. A method of preparing a composition for the treatment of liver disease, the method comprising:

(i) obtaining a population of undifferentiated multipotent stromal cells (MSCs);

(ii) culturing the MSCs in a medium;

(iii) obtaining the medium resulting from the culturing of (ii);

(iv) formulating a selected fraction of the medium obtained in (iii) to form a composition for administration to a mammal wherein the fraction has been selected based on its capability of one or both of promoting hepatocyte proliferation or inhibiting hepatocyte death.