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COMPOSITION FOR VASCULAR REGENERATION THERAPY, CONTAINING DEDIFFERENTIATED FAT CELLS AS ACTIVE INGREDIENT meetings

Foreign code F170008941
File No. (S2015-0856-N0)
Posted date Jan 20, 2017
Country WIPO
International application number 2016JP059386
International publication number WO 2016158670
Date of international filing Mar 24, 2016
Date of international publication Oct 6, 2016
Priority data
  • P2015-065598 (Mar 27, 2015) JP
Title COMPOSITION FOR VASCULAR REGENERATION THERAPY, CONTAINING DEDIFFERENTIATED FAT CELLS AS ACTIVE INGREDIENT meetings
Abstract The present invention addresses the problem of providing a cell for use in a vascular regeneration therapy, which has a superior blood flow-improving effect compared with a bone marrow-derived MSC, an ASC or the like that is a conventional cell for use in a therapy, and which can be obtained easily in an amount sufficient enough for transplantation, and which has stable quality. It is found that a human DFAT has a high neovascularization ability, can exhibit a high proliferation ability after being subcultured and therefore can be produced easily in an amount needed for transplantation, and does not undergo transformation. Therefore, it is found for the first time that a human DFAT is effective for a vascular regeneration therapy for a human body. These findings lead to the accomplishment of the present invention. That is, the present invention provides a blood flow-improving agent containing human dedifferentiated fat cells (human DFAT) as an active ingredient.
Outline of related art and contending technology BACKGROUND ART
Conventional, drug therapy and surgical therapy refractory not adapted peripheral arterial disease (hereinafter, simply referred to as PAD) to, autologous bone marrow mononuclear cells were (i) in the ischemic angiogenesis therapy is performed by administering, its effectiveness has been confirmed (TACT study). Then, G-CSF mobilization (ii) peripheral blood mononuclear cells, adipose tissue-derived stromal vascular fraction (SVF) (iii) cells, peripheral blood mononuclear cells (iv), (v) CD34 positive cells G-CSF mobilization, bone marrow-derived CD133 positive cells (vi), (vii) cultured bone marrow mesenchymal stem cells (MSC) (viii) culturing adipose tissue-derived stem cells (ASC) in the same manner as in many forms such as angiogenic therapy using autologous cells has been performed. (I) - (viii) of the above, (vi) - (i) does not perform cell culture, the necessary number of cells in order to obtain large amounts of tissue be needed for high invasiveness and given to the patient. For this reason the collection with a relatively low-invasive (iv) normal 1 except that the number of treatment only once. In addition, (iv) - (i) cells, because the miscellaneous cell population, and safety of the implantation effects is not constant. In addition, (v), (vi) cells, the stem cell marker using the antibodies selected in uniformity of cells by performing an operation can be improved, the complexity associated with preparing the antibody screening efficiency, and thus increases the cost for preparing the problem. (Vii) 10 ml of the cells are harvested and the number of bone marrow fluid, and then used adhesion culture and propagate, (viii) cells, adipose tissue in an enzyme treatment, in the same manner as (vii) to use the adhesion culture and propagate. Therefore, (vii), (viii) cells together, a large amount from a relatively small amount of tissue that can be prepared that has an advantage of being, the method includes traces in adult tissue stem cell is cultured, grown in the method of the invention, it is unavoidable that the cells are mixed into the other, in order to obtain the necessary number of cells in the treatment of culture needs to be repeated several times. The number of treatment is usually performed only once in the 1. The performance of a cell such as the ability to propagate and other individual differences, age, easily influenced by the underlying disease a demerit that. (i) - (Viii) is the problem that common cells, in proportion to the treatment cost, performance and other individual differences, the number of cells required is not obtained (non-responder) and a treatment not cases the presence, in consideration of invasion of the patient and the normal 1 remain in a single treatment, in. At the present time, with the cells of these peripheral arterial disease (PAD) refractory many clinical studies have been made, placebo, control test cells does not yet have a significant effect. Also, in addition to this, rat adipose tissue-derived progenitor cells or a rat adipose tissue-derived mesenchymal stem cells of blood vessels disclosed to be effective (Patent Document 1, 2). The inventors of the present invention, of a non-human animal such as a mouse mature adipocytes derived from adipose tissue to induce de-differentiation of preadipocytes as de-differentiated adipocytes (DFAT) for the first time to establish (Patent Document 3) can be successful, it is possible to induce the differentiation of DFAT, osteoblasts, myoblasts, chondrocytes, can acquire the functions of nerve cells has been shown (patent document 4). In addition, the inventors of the present invention, mouse and rat DFAT angiogenesis can be used together has been clearly positioned in the (non-patent document 1-3). However, a mouse or a rat DFAT attached and of low capacity to proliferate after implantation and increased up to the necessary number of the difficult, transformed by subculture Bench (immortalized) resulting in a higher possibility of the tumor may be implanted safely. For these reasons, in a mouse or a rat human DFAT DFAT of the same phenomenon occurs, is not suitable for the treatment and it has been considered.
Scope of claims (In Japanese)[請求項1]
ヒト脱分化脂肪細胞(ヒトDFAT)を有効成分とする血流改善剤。
[請求項2]
ヒト脱分化脂肪細胞(ヒトDFAT)を有効成分とする血管新生促進剤。
[請求項3]
ヒト脱分化脂肪細胞(ヒトDFAT)を有効成分とする虚血性疾患治療剤。
[請求項4]
虚血性疾患が末梢動脈疾患(PAD)または虚血性心筋症である、請求項3に記載の虚血性疾患治療剤。
[請求項5]
ヒト脱分化脂肪細胞(ヒトDFAT)が、1~4代継代培養されたヒト脱分化脂肪細胞(ヒトDFAT)である、請求項1~4のいずれかに記載の剤。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NIHON UNIVERSITY
  • Inventor
  • MATSUMOTO, Taro
  • KANO, Koichiro
  • KAZAMA, Tomohiko
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 DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR 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 SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN 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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