TOP > 外国特許検索 > Activator for mesenchymal stem cells, activated mesenchymal stem cells, and method for producing same

Activator for mesenchymal stem cells, activated mesenchymal stem cells, and method for producing same NEW

外国特許コード F180009488
整理番号 13008-EP01
掲載日 2018年10月30日
出願国 欧州特許庁(EPO)
出願番号 15761691
公報番号 3118307
出願日 平成27年3月11日(2015.3.11)
公報発行日 平成29年1月18日(2017.1.18)
国際出願番号 JP2015057217
国際公開番号 WO2015137419
国際出願日 平成27年3月11日(2015.3.11)
国際公開日 平成27年9月17日(2015.9.17)
優先権データ
  • 20140-048202 JP
  • 2015JP57217 (2015.3.11) WO
発明の名称 (英語) Activator for mesenchymal stem cells, activated mesenchymal stem cells, and method for producing same NEW
発明の概要(英語) [Problem] To activate an abnormal mesenchymal stem cell whose therapeutic effect is lost or reduced, or rather which has a disease-exacerbating effect so as to be in a state suitable for cell transplant therapy.
[Solution] An activator for mesenchymal stem cells, mesenchymal stem cells activated by the activator, a method for producing the same, and a pharmaceutical containing the activated mesenchymal stem cells are provided.
従来技術、競合技術の概要(英語) Background Art
Globally, the number of diabetic patients continuously increases.Various complications caused by chronic hyperglycemia due to diabetes threaten QOL and life of the patients, which has become a serious problem.
The so-called three major diabetic complications: diabetic nephropathy, diabetic retinopathy and diabetic neuropathy are developed due to organ damage caused by microangiopathy, which is a pathological change occurring in thin blood vessels, mainly capillaries.These complications can be prevented to a certain extent by appropriately controlling blood glucose with dietary therapy, drug therapy or the like.However, when the complications become serious, there is no fundamental therapy.
It is known that mesenchymal stem cells (hereinafter, also referred to as "MSCs") are cells capable of differentiating into not only mesenchymal cells but also diverse cells beyond the germ layer and have an ability of controlling the tissue development, repair and reproduction.
Since the isolation and cultivation of mesenchymal stem cells are easy and mesenchymal stem cells have a vigous proliferation potential, it is possible to ensure the number of transplantable cells in a short period.In addition, mesenchymal stem cells can be transplanted autologously with no immunological rejection, which causes few ethical problems.Furthermore, allogenic transplantation of mesenchymal stem cells without pretreatment is realistic because of their low immunogenicity.Accordingly, the therapeutic applications of mesenchymal stem cells as a material for ideal cell transplant therapy for diverse diseases are proceeding.
For example, the therapeutic effects of mesenchymal stem cells have been confirmed in diabetes and its complications described above (Non Patent Literatures 1 and 2) as well as diseases such as brain and cardiovascular disease (Patent Literature 1), autoimmune disease (Non Patent Literature 3), experimental autoimmune encephalomyelitis model of multiple sclerosis (Non Patent Literature 4), and inflammatory disease (refer to Non Patent Literature 5 on pulmonary fibrosis model, refer to Non Patent Literature 6 on inflammatory bowel disease) .
When used for disease therapy, it is necessary to prepare mesenchymal stem cells with a certain level of quality rapidly and in a large amount.In order to allow the mesenchymal stem cells obtained from donors to proliferate in vitro, growth promoting substances, cell culture substrates and the like are variously examined.For example, Patent Literature 2 discloses that an umbilical cord extract can be used as a serum alternative on cultivation of stem cells in a serum free medium.Concerning the quality of cells, for example, Patent Literature 3 discloses a cell growth medium for suppressing senescence of mesenchymal stem cells during subculturing.
However, the umbilical cord extract disclosed in Patent Literature 2 is simply the serum alternative.The medium in Patent Literature 3 intends to maintain the quality or suppress the degree of deterioration of mesenchymal stem cells during in vitro proliferation, and does not improve or modify the quality of mesenchymal stem cells that are not appropriate for therapy, i.e. low quality mesenchymal stem cells.
Citation List
Patent Literatures
Patent Literature 1: WO2005/007176
Patent Literature 2: WO2013/009100
Patent Literature 3: JP2006-325444 A

Non-Patent Literatures
Non-Patent Literature 1: Ezquer, F. E. et al., Biol Blood Marrow Transplant, 2008; 14 (6): 631-40
Non-Patent Literature 2 : Lee, R. H. et al. , Proc Natl Acad Sci USA, 2006; 103 (46): 17438-43
Non-Patent Literature 3 : Dj ouad, F. et al. , Arthritis Rheum, 2005; 52(5): 1595-1603
Non-Patent Literature 4: Zappia E. et al., Blood 2005; 106: 1755-1761
Non-Patent Literature 5: Ortiz, A. L. et al., Proc Natl Acad Sci USA, 2003; 100 (14): 8407-8411
Non-Patent Literature 6: Tanaka H. et al. , J Gastroenterol, 2011; 46: 143-152

特許請求の範囲(英語) [claim1]
1. An activator for abnormal mesenchymal stem cell, including an extract from mammalian fetal appendage as an active ingredient.
[claim2]
2. The activator according to Claim 1, wherein the fetal appendage is an umbilical cord tissue, a placental tissue or a placental membrane.
[claim3]
3. The activator according to Claim 1 or 2, wherein the extract does not contain cells that are derived from the mammal and have proliferation potency.
[claim4]
4. The activator according to any one of Claims 1 to 3, wherein the abnormal mesenchymal stem cell is a bone-marrow-derived mesenchymal stem cell.
[claim5]
5. The activator according to any one of Claims 1 to 4, wherein the abnormal mesenchymal stem cell is separated from a subject with a disease.
[claim6]
6. The activator according to Claim 5, wherein the disease is diabetes, an autoimmune disease, a chronic inflammatory disease, an allergic disease or osteoporosis.
[claim7]
7. The activator according to Claim 5, wherein the disease is diabetes or rheumatoid arthritis.
[claim8]
8. A method for producing an activated mesenchymal stem cell including:
treating an abnormal mesenchymal stem cell separated from a subject with an activator that includes an extract from mammalian fetal appendage as an active ingredient.
[claim9]
9. The method for producing a mesenchymal stem cell according to Claim 8, wherein the abnormal mesenchymal stem cell is a bone-marrow-derived mesenchymal stem cell.
[claim10]
10. The method for producing a mesenchymal stem cell according to Claim 8 or 9, wherein the subject is a subject with a disease.
[claim11]
11. The method for producing a mesenchymal stem cell according to Claim 10, wherein the disease is diabetes, an autoimmune disease, a chronic inflammatory disease, an allergic disease or osteoporosis.
[claim12]
12. The method for producing a mesenchymal stem cell according to Claim 10, wherein the disease is diabetes or rheumatoid arthritis.
[claim13]
13. A mesenchymal stem cell for the treatment and/or prevention of a disease, wherein the cell is produced by the method according to any one of Claims 8 to 12.
[claim14]
14. The mesenchymal stem cell according to Claim 13, wherein the disease is diabetes or its complications, an autoimmune disease, a chronic inflammatory disease, an allergic disease or osteoporosis.
[claim15]
15. The mesenchymal stem cell according to Claim 13, wherein the disease is diabetic nephropathy, diabetic retinopathy, diabetic neuropathy or rheumatoid arthritis.
[claim16]
16. A pharmaceutical for the treatment and/or prevention of a disease including the mesenchymal stem cell according to any one of Claims 13 to 15 and/or its culture.
  • 出願人(英語)
  • SAPPORO MEDICAL UNIVERSITY
  • 発明者(英語)
  • FUJIMIYA MINEKO
  • NAGAISHI KANNA
  • MIZUE YUKA
  • CHIKENJI TAKAKO
国際特許分類(IPC)
指定国 Contracting States: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

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