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DISEASE MODEL

Foreign code F200010233
File No. (S2019-0209-N0)
Posted date Oct 29, 2020
Country WIPO
International application number 2020JP003159
International publication number WO2020158794
Date of international filing Jan 29, 2020
Date of international publication Aug 6, 2020
Priority data
  • P2019-014778 (Jan 30, 2019) JP
Title DISEASE MODEL
Abstract The present invention provides a method for producing a disease model, the method including a step for introducing cancer cells or fibroblasts into recellularized organs or tissue.
Outline of related art and contending technology BACKGROUND ART
Cancer is 1 major factors of human death. Studies on methods of treatment of cancer have been actively progressed, but the 5-year survival rate remains low, for example, in the case of lung cancer, the 5-year survival rate of lung cancer patients remains at about 15 %. In recent years, development of anticancer agents targeting molecules expressed in cancer has been progressed, and as the target 1, epidermal growth factor receptor (EGFR), which is recognized to be overexpressed in various malignant tumors such as non-small cell lung cancer (NSCLC), has been focused. For example, it has been reported that administration of a EGFR inhibitor has an antitumor effect to NSCLC patients with a EGFR mutation that causes EGFR activation. However, there is also reported a problem that the number of patients having the gene mutation is small, and the secondary mutation of the gene causes cancer cells to have drug resistance, for example, Non-Patent Document 1). Therefore, in order to provide drugs and combinations of drugs for treating diseases such as cancer suitable for individual patients, it is believed that understanding of biological mechanisms of diseases including diversity and mechanism of acquisition of resistance is indispensable (, for example, Non-Patent Document 2).
Fibrosis is a disease in which abnormal accumulation of fibrotic tissue due to tissue damage, autoimmune reaction, and the like is recognized, and fibrosis in various organs and tissues such as lung, liver, pancreas, kidney, heart, bone marrow, and skin is known in humans. Fibrosis whose cause can be identified is often cured by removal of the cause or administration of anti-inflammatory agents such as steroids. On the other hand, steroids and immunosuppressants are generally used for the treatment of pulmonary fibrosis and interstitial pneumonia accompanied by fibrosis, but there is no effective treatment method for improving prognosis.
In addition, in the development of anticancer agents, there are many cases in which development of anticancer agents is forgotten due to clinical failure in the late stage of clinical trials of Phase II and Phase III, for example, Non-Patent Document 3). 1 for this reason is the lack of a model system capable of accurately predicting pharmacological effects. Although the response of cancer to a drug is affected by complex interactions of several factors, including tissue-specific microenvironments, mechanical stimuli, etc., it is very difficult to assess these effects in conventional two-dimensionally cultured cells. Therefore, it is desired to develop a model system which reproduces a disease, especially a disease model having a three-dimensional structure, which is useful for elucidating biological mechanisms of diseases such as cancer and fibrosis, and can predict therapeutic effects on the disease more accurately.
Incidentally, in the field of transplantation, there is a great expectation toward a decellularized organ in which a decellularized organ skeleton is decellularized by its own cell. Decellularized tissue skeletons are relatively easily obtained from tissues and organs of animals and humans, and therefore are widely used as medical materials in practical clinical practice. Biological valves (HANCOK II (R), PERIMOUNT Magna (R), human biological valve (Synegraft) (R)) and the like derived from pig or cow are used as the medical material in the cardiovascular surgery area, Human derived skin (AlloDerm (®)), pig small intestine (OASIS (®)), artificial bone (AlloCraft C-Ring (®)), and the like are used in the area of the orthopedic surgery. Engraftment of "autologous cells" to these medical materials used in clinical theory makes it possible to create autologous organs from other types of organs. (, for example, Non-Patent Document 4), has been reported as a method for engraftment of a self cell or the like, a method for engraftment of a self cell or the like by engraftment of the self cell to the organ on decellularization of the organ to produce a recellular organ. However, as long as the inventors know, it has not been reported that a disease model could be produced from a recellular organ.
Scope of claims (In Japanese)[請求項1]
 再細胞化された臓器又は組織にがん細胞又は線維芽細胞を導入する工程を含む、疾患モデルを製造する方法。

[請求項2]
 前記臓器又は組織が肺又は肺組織である、請求項1に記載の方法。

[請求項3]
 前記がん細胞が肺がん細胞である、請求項1又は2に記載の方法。

[請求項4]
 前記がん細胞が、A549細胞、PC-9細胞、H520細胞、H1975細胞、HCC827細胞及びPC-6細胞からなる群から選択される1種以上の細胞である、請求項1~3のいずれか1項に記載の方法。

[請求項5]
 前記再細胞化された肺又は肺組織が、脱細胞化された肺又は肺組織に上皮細胞及び内皮細胞を導入することにより製造された肺又は肺組織である、請求項2~4のいずれか1項に記載の方法。

[請求項6]
 請求項1~5のいずれか1項に記載の方法により製造された疾患モデル。

[請求項7]
 前記疾患モデルが肺疾患モデルである、請求項6に記載の疾患モデル。

[請求項8]
 (1)請求項6又は7に記載の疾患モデルに被験物質を接触させる工程、及び
 (2)該被験物質と接触させる前の疾患モデル又は該被験物質と接触させていない疾患モデルと比較して、該被験物質との接触によりがん細胞若しくは線維芽細胞の数が減少した、又は該細胞の増殖速度が低下した場合に、該被験物質を疾患の治療又は予防の候補物質として選別する工程
を含む、疾患の治療又は予防剤のスクリーニング方法。

[請求項9]
 前記疾患が肺疾患である、請求項8に記載の方法。

[請求項10]
 (1)請求項6又は7に記載の疾患モデルに被験物質を接触させる工程、及び
 (2)該被験物質との接触による疾患モデルの損傷の程度を評価する工程
を含む、該被験物質の副作用の評価方法。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NAGASAKI UNIVERSITY
  • Inventor
  • TSUCHIYA, Tomoshi
  • NAGAYASU, Takeshi
  • MIZOGUCHI, Satoshi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN WS ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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