Pharmaceutical composition comprising glia-like cells induced from late-passage human mesenchymal stem cells as active ingredient for treatment of stroke

Patent metadata

Field	Value
Publication number	US-2022331368-A1
Application number	US-202017615570-A
Country	US
Kind code	A1
Filing date	Aug 24, 2020
Priority date	Aug 22, 2019
Publication date	Oct 20, 2022
Grant date	—

Abstract

The present invention relates to a pharmaceutical composition comprising glia-like cells differentiated from human mesenchymal stem cells as an active ingredient for treatment of stroke. Specifically, as a result of injecting the glia-like cells differentiated from human mesenchymal stem cells (ghMSCs) of the present invention to cerebral infarction-induced animal models, the infarct volume remarkably decreased by 50% or more and neural functions were remarkably improved, compared to a control group and a group treated with human mesenchymal stem cells (hMSCs), demonstrating that ischemic stroke (infarction) is treated by the Akt pathway of IGFBP-4 via IGF-1R. Thus, the differentiated glia-like cells of the present invention can be advantageously used as a cell therapy product for stroke.

First claim

1 . A method for treating stroke in a subject comprising:
administering an effective amount of glia-like cells (ghMSCs) to the subject, wherein in the ghMSCs are induced from late-passage human mesenchymal stem cells (hMSCs), thereby treating the subject.

2 . The method for treating stroke according to claim 1 , wherein the ghMSCs are oligodendroglia, astrocytes, microglia, radial glia, or a combination thereof.

3 . The method for treating stroke according to claim 1 , wherein the stroke is ischemic stroke or hemorrhagic stroke.

4 . The method for treating stroke according to claim 1 , wherein the late-passage hMSCs have been passaged 10 to 15 times.

5 . The method for treating stroke according to claim 1 , wherein the ghMSCs are derived from bone marrow, adipose tissue, blood, umbilical cord blood, liver, skin, gastrointestinal tract, placenta or uterus.

6 . The method for treating a stroke according to claim 1 , wherein the ghMSCs release IGFBP-4 (insulin-like growth factor binding protein-4).

7 . The method for treating stroke according to claim 1 , wherein the ghMSCs activate the PI3K/Akt pathway of IGFBP-4 via IGF-1R.

8 . The method for treating stroke according to claim 1 , wherein the ghMSCs are administered at a density of 6×10 5 ˜6×10 7 cells/kg.

9 . The method for treating stroke according to claim 1 , wherein the ghMSCs are adminstered as a cell therapy product.

10 . The method for treating stroke according to claim 1 , wherein the ghMSCs are administered parenterally.

11 . A method for producing late-passage human mesenchymal stem cells (hMSCs) induced into glia-like cells (ghMSCs) comprising the following steps:
1) obtaining late-passage human mesenchymal stem cells by culturing human mesenchymal stem cells; 2) primary culturing the late-passage human mesenchymal stem cells obtained in step 1) for 22˜26 hours in DMEM containing 10% FBS and 1 mM β-mercaptoethanol; 3) secondary culturing the late-passage human mesenchymal stem cells for 68˜76 hours in DMEM containing 10% FBS and 0.28 μg/ml of tretinoin (all-trans-retinoic acid); and 4) tertiary culturing the late-passage human mesenchymal stem cells for 8 days in DMEM containing 10% FBS, 10 ng/ml of bFGF (basic fibroblast growth factor), 5 ng/ml of PDGF-AA, 10 μM Forskolin and 200 ng/ml of HRG-β1 (Heregulin-β1).

12 . A composition for intra-individual IGFBP-4 (insulin-like growth factor binding protein-4) delivery comprising late-passage glia-like cells (ghMSCs) differentiated from human bone marrow-derived mesenchymal stem cells as an active ingredient.

13 . A method for treating stroke comprising a step of:
administering late-passage human mesenchymal stem cells (hMSCs) induced into glia-like cells (ghMSCs) to a subject.

Assignees

• Seoul Nat Univ R&Db Foundation
• Iucf Hyu

Inventors

• Chang Mi-Sook
• Koh Seong-Ho

Classifications

• A61P9/10 Primary

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K35/30 Primary

  Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue · CPC title

• A61K35/28

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• C12N2506/1346

  from mesenchymal stem cells · CPC title

• C12N5/0622

  Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells · CPC title