Compositions, methods, and devices for treating disease

Patent metadata

Field	Value
Publication number	US-2016331784-A1
Application number	US-201514967028-A
Country	US
Kind code	A1
Filing date	Dec 11, 2015
Priority date	Oct 11, 2006
Publication date	Nov 17, 2016
Grant date	—

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.

First claim

1 . A system for treating blood or plasma from a mammal, the system comprising an extracorporeal bioreactor (EB) comprising a fluid treatment compartment and a cell compartment, and a selectively permeable barrier separating the fluid treatment compartment and the cell compartment, wherein the cell compartment comprises a population of undifferentiated multipotent stromal cells (MSCs).

2 . The system of claim 1 , wherein the cell compartment further comprises a population of primary hepatocytes.

3 . The system of claim 1 , wherein the selectively permeable barrier comprises a bundle of hollow fibers.

4 . The system of claim 1 , wherein the EB further comprises a biological fluid inlet and a biological fluid outlet, wherein the biological fluid inlet and outlet permit fluid communication between the fluid treatment compartment and a bloodstream of the mammal.

5 . The system of claim 1 , further comprising a plurality of pumps for circulating the blood or plasma through the fluid treatment compartment.

6 . The system of claim 1 , the system further comprising an ultrafiltration cartridge in fluid communication with the fluid treatment compartment.

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15 . 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; (iv) fractionating the medium; (v) selecting a fraction of the medium that is capable of one or both of promoting hepatocyte proliferation or inhibiting hepatocyte death; and (vi) optionally, formulating the selected fraction for administration to a mammal.

16 . The method of claim 15 , wherein the composition is concentrated 25-fold.

17 . The method of claim 16 , wherein the medium comprises a serum free tissue culture medium or phosphate buffered saline (PBS).

18 . The method of claim 15 , further comprising lyophilizing the composition.

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28 . A method for identifying a biologically active compound for the treatment of a liver disease, the method comprising;
(a) obtaining one or more fractions of a medium containing factors secreted from a population of undifferentiated multipotent stromal cells (MSCs); (b) assaying the ability of one or more of the fractions to promote one or both of hepatocyte proliferation or inhibit hepatocyte death; (c) selecting a fraction of the medium that promotes one or both of hepatocyte proliferation or inhibit hepatocyte death; and (d) identifying one or more molecules present in the selected fraction.

29 . The method of claim 28 , wherein the fractions are obtained according to size.

30 . The method of claim 28 , wherein the fractions are obtained according to charge.

31 . The method of claim 28 , wherein the fraction of the medium is a heparin sulfate binding fraction of the medium.

Assignees

• The General Hospital Corp D/B/A Massachusetts General Hospital
• Massachusetts Inst Technology

Inventors

• Yarmush Martin Leon
• Parekkadan Biju

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61M1/3687

  Chemical treatment (A61M1/3675 takes precedence) · CPC title

• C12M29/16

  Hollow fibers (hollow fiber modules in general B01D63/02) · CPC title

• C12N2502/1358

  Bone marrow mesenchymal stem cells (BM-MSC) · CPC title

• A61M1/3489

  by biological cells, e.g. bioreactor · CPC title