Title:
CELL SHEET CONTAINING PERIPHERAL BLOOD MONONUCLEAR CELLS OR FIBROBLASTS ASSOCIATED WITH FACTOR SECRETED BY PERIPHERAL BLOOD MONONUCLEAR CELLS
Document Type and Number:
WIPO Patent Application WO/2016/068217
Kind Code:
A1
Abstract:
The present invention provides a cell sheet that is useful for treating intractable skin ulcers, and a method for producing the cell sheet. Specifically provided are: a cell sheet that sufficiently improves the healing of an ischemic ulcer in which blood circulation is inadequate by transplanting the cell sheet to the ulcer site, without producing an immune rejection reaction such as a reaction induced by an artificial dermis or the like; and a method for producing the cell sheet. The present invention involves a cell sheet that contains peripheral blood mononuclear cells and fibroblasts, and a cell sheet that contains fibroblasts that have been stimulated by a transforming growth factor or platelet-derived growth factor. The amount of blood vessel growth factor, which plays an important role in angiogenesis, produced in said sheet significantly increases, and upon transplanting said sheet to a skin ulcer site produced on the back of diabetic mouse, the cure rate of the wound site is significantly improved compared to transplanting the cell sheet with fibroblasts alone. In addition, by using cells acquired from a patient for the peripheral blood mononuclear cells and fibroblasts of the present invention, an immune rejection reaction to transplantation can be suppressed.
Inventors:
HAMANO KIMIKAZU (JP)
HOSOYAMA TOHRU (JP)
UENO KOJI (JP)
HOSOYAMA TOHRU (JP)
UENO KOJI (JP)
Application Number:
PCT/JP2015/080465
Publication Date:
May 06, 2016
Filing Date:
October 28, 2015
Export Citation:
Assignee:
UNIV YAMAGUCHI (JP)
International Classes:
C12N5/077; A61K35/14; A61K35/36; A61L15/16; A61L27/00; A61P17/02; C12N5/078
Foreign References:
| JP2003190273A | 2003-07-08 | |||
| JP2010046058A | 2010-03-04 | |||
| JP2012506258A | 2012-03-15 | |||
| JP2012044905A | 2012-03-08 | |||
| JP2013523720A | 2013-06-17 | |||
| JPS63214185A | 1988-09-06 |
Other References:
YAMANAKA, O. ET AL.: "Connective tissue growth factor modulates extracellular matrix production in human subconjunctival fibroblasts and their proliferation and migration in vitro.", JPN. J. OPHTHALMOL., vol. 52, no. 1, 2008, pages 8 - 15, ISSN: 0021-5155
FAWZI-GRANCHER, S. ET AL.: "Optimisation of biochemical condition and substrates in vitro for tissue engineering of ligament.", ANN. BIOMED. ENG., vol. 34, no. 11, November 2006 (2006-11-01), pages 1767 - 1777, ISSN: 0090-6964
TROMPEZINSKI, S. ET AL.: "Transforming growth factor-bl and ultraviolet Al radiationincrease production of vascular endothelial growth factor butnot endothelin-1 in human dermal fibroblasts.", BR. J. DERMATOL., vol. 143, no. 3, September 2000 (2000-09-01), pages 539 - 545, ISSN: 0007-0963
MANABU NONAKA ET AL.: "Distinct responsiveness of nasal fibroblasts to TGF-beta", MEN'EKI ALLERGY, vol. 19, no. 1, 2001, pages 1 - 4, ISSN: 0913-0691
FINKENZELLER, G. ET AL.: "Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C.", CANCER RES., vol. 52, no. 17, 1 September 1992 (1992-09-01), pages 4821 - 4823, ISSN: 0008-5472
KOJI UENO ET AL.: "Masshoketsu Tankakukyu to Sen'iga Saibo kara naru Saibo K onzai Sheet o Mochiita Nanjisei Hifu Kaiyo Chiryo no Kisoteki Kento", REGENERATIVE MEDICINE, vol. 14, 1 February 2015 (2015-02-01), pages 270, ISSN: 1347-7919
FAWZI-GRANCHER, S. ET AL.: "Optimisation of biochemical condition and substrates in vitro for tissue engineering of ligament.", ANN. BIOMED. ENG., vol. 34, no. 11, November 2006 (2006-11-01), pages 1767 - 1777, ISSN: 0090-6964
TROMPEZINSKI, S. ET AL.: "Transforming growth factor-bl and ultraviolet Al radiationincrease production of vascular endothelial growth factor butnot endothelin-1 in human dermal fibroblasts.", BR. J. DERMATOL., vol. 143, no. 3, September 2000 (2000-09-01), pages 539 - 545, ISSN: 0007-0963
MANABU NONAKA ET AL.: "Distinct responsiveness of nasal fibroblasts to TGF-beta", MEN'EKI ALLERGY, vol. 19, no. 1, 2001, pages 1 - 4, ISSN: 0913-0691
FINKENZELLER, G. ET AL.: "Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C.", CANCER RES., vol. 52, no. 17, 1 September 1992 (1992-09-01), pages 4821 - 4823, ISSN: 0008-5472
KOJI UENO ET AL.: "Masshoketsu Tankakukyu to Sen'iga Saibo kara naru Saibo K onzai Sheet o Mochiita Nanjisei Hifu Kaiyo Chiryo no Kisoteki Kento", REGENERATIVE MEDICINE, vol. 14, 1 February 2015 (2015-02-01), pages 270, ISSN: 1347-7919
Attorney, Agent or Firm:
OKUHARA Koji et al. (JP)
Yasushi Okuhara (JP)
Yasushi Okuhara (JP)
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