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Prophylactic or therapeutic agent for organ fibrosis

A fibrosis and organ technology, applied in the field of cell preparation of pluripotent stem cells, to achieve the effect of improving function

Pending Publication Date: 2019-04-26
TOHOKU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no clear disclosure of the use of Muse cells in the prevention and / or treatment of fibrosis and the expected therapeutic effect

Method used

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  • Prophylactic or therapeutic agent for organ fibrosis
  • Prophylactic or therapeutic agent for organ fibrosis
  • Prophylactic or therapeutic agent for organ fibrosis

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0070] (2) Preparation and use of cell preparations

[0071] The cell preparation of the present invention is not limited, and can be obtained by suspending the Muse cells obtained in (1) above or a cell population containing Muse cells in physiological saline or an appropriate buffer (eg, phosphate-buffered saline). In this case, if the number of Muse cells isolated from autologous or non-autologous tissue is small, the cells may be cultured and proliferated before cell transplantation until a given number of cells can be obtained. It should be noted that, as already reported (International Publication No. WO2011 / 007900), Muse cells do not become tumors, so even if the cells recovered from the living tissue are directly contained in an undifferentiated form, the possibility of canceration Also lower is safe. In addition, the culture of recovered Muse cells is not particularly limited, and can be performed in a common growth medium (for example, α-minimal essential medium (α-...

Embodiment 1

[0083] Transplantation of Human Muse Cells to Liver Fibrosis Model Mice

[0084] All studies use CB17 / Icr-Prkdc / CrlCrlj (SCID) mice. All animal experiments were performed in accordance with the guidelines for the humane care and use of experimental animals of Tohoku University (Sendai, Japan). The experimental procedures for making liver fibrosis models also refer to International Journal of Molecular Science 2012; 13:3598-3617 and Journal of Biochemistry 2003; 134:551-558. Specifically, by using CCl 4 (0.5ml / kg) intraperitoneal injection to make the liver fibrosis model of SCID mice.

[0085] Human Muse cells or non-Muse cells (5×10 4 cells) into the tail vein of liver fibrosis model mice.

[0086] Statistical Analysis

[0087] Significant differences between the two groups were assessed using the Student's t-test. Statistically significant differences between more than 3 groups were evaluated using one-way ANOVA with Bonferroni's multiple comparison test. Th...

Embodiment 2

[0112] Evaluation of Muse cells in skin fibrosis model

[0113] According to the method described in Sci Rep.2015Aug 20;5:12466.doi:10.1038 / srep12466., a BLM-induced skin fibrosis model mouse was produced. As mice, C57BL / 6J, female (Nippon SLC Co., Ltd.) was used. Physiological saline was administered instead of BLM in the control group.

[0114] On day 14 from BLM administration, 1 × 10 6 Cells / body weight (kg) of Muse cells. On the other hand, the vehicle administration group was administered the vehicle from the tail vein on day 14.

[0115] On day 28 from BLM administration, skin tissue was isolated, and collagen quantification, hematoxylin-eosin (HE) staining, and thickness analysis of the dermal layer were performed.

[0116] Skin collagen analysis was performed as described below.

[0117] Skin pieces were homogenized using 0.5M acetic acid / pepsin solution and stirred overnight at 4°C. Using the obtained extract, the skin collagen concentration was me...

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Abstract

The present invention addresses the problem of providing a safe and easy-to-prepare cell preparation for prevention and / or treatment of organ fibrosis such as liver fibrosis. Provided is a cell preparation for prevention and / or treatment of organ fibrosis such as liver fibrosis, the cell preparation including a SSEA-3-positive pluripotent stem cell (Muse cell) derived from a vital mesenchymal tissue or a cultured mesenchymal cell.

Description

technical field [0001] The present invention relates to cell preparations in regenerative medicine. More specifically, it relates to a cell preparation containing pluripotent stem cells effective for the repair and regeneration of fibrotic organs. Background technique [0002] Organ fibrosis refers to the accumulation of infection, inflammation, fat and other substances in the living body caused by various reasons (including unknown reasons) such as microorganisms, chemical substances, immune reactions, etc., dietary habits, environment, genetic background, etc. , tissue or cell degeneration, etc. lead to organ damage, necrosis, etc., cannot fully regenerate, connective tissue increases and fibrosis occurs, and the resulting diseases are known to occur in the liver, lungs, heart, kidneys, brain nervous system, etc. In addition to various organs, it occurs in many organs and tissues such as muscles, bones, and skin. [0003] Liver cirrhosis is the fibrosis that occurs in th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/545A61P1/00A61P1/16A61P5/00A61P9/00A61P11/00A61P13/00A61P15/00A61P17/00A61P25/00
CPCA61P1/16A61P1/00A61P25/00A61P11/00A61P15/00A61P13/00A61P9/00A61P17/00A61P5/00A61K35/545A61P17/02A61P43/00A61K35/28
Inventor 出泽真理海野伦明山本登志弘神藤康弘原启人桝富直哉
Owner TOHOKU UNIV
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