JP5956422B2 - 糖尿病治療のためのテンプレート島細胞および小型島細胞クラスター - Google Patents
糖尿病治療のためのテンプレート島細胞および小型島細胞クラスター Download PDFInfo
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Description
本出願は、米国特許出願第11/589,063号(2006年10月30日出願)の一部継続である。上記出願は、参照により本明細書中で援用される。
(連邦政府による資金提供を受けた研究または開発に関する陳述)
この明細書中で引用される特許出願、特許および出版物はすべて、これらの記載内容が参照により本明細書中で援用される。矛盾する場合は、本発明の開示(定義を含む)が優先される。
B. 多層として付着される島細胞
C. ディボット化微小鋳型上の島の産生
ラット島単離
収率
生存度
移植試験
実施例2:個々の島細胞または小型島細胞クラスターへの大型島の変換
a. 酵素消化
b. 金属ベースの断片化
c. 酵素消化および金属分散液の組合せ
実施例3:パッチ生体物質足場上での個々の島細胞および小型島クラスターの調製
足場物質のスクリーニング
島細胞パッチの調製
実施例4:生体物質足場上の島細胞の予測試験
実施例5:微小鋳型を用いた最適サイズ化細胞の調製
微小鋳型の開発
微小鋳型内の細胞再凝集
以下の参考文献は、それらが本明細書中に記述されるものを補足する例示的手法的またはその他の詳細を提供する範囲で、参照により本明細書中で援用される。
SU-8 2000 - Permanent Epoxy Negative Photoresist, MicroChem, Newton, MA.
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Bosco D, Armanet M, Morel P, Niclauss N, Sgroi A, Muller YD, Giovannoni L, Parnaud G, Berney T, Unique arrangement of alpha- and beta-cells in human islets of Langerhans, Diabetes. Feb 25. [Epub ahead of print] (2010).
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Crim WS, Wu R, Carter JD, Cole BK, Trace AP, Mirmira RG, Kunsch C, Nadler JL, Nunemaker CS. AGI-1067, a novel antioxidant and anti-inflammatory agent, enhances insulin release and protects mouse islets.Mol Cell Endocrinol. Mar 6. [Epub ahead of print] (2010).
Cui Y-F, Ma M, Wang G-Y, D-E. H, Vollmar B, and Menger MD, Prevention of core cell damage in isolated islets of Langerhans by low temperature preconditioning, World J Gastroenter 11: 545-550, (2005).
Dean et al., Comparison of insulin autoantibodies in diabetes-related and healthy populations by precise displacement ELM, Diabetes (1989).
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Kaihow T, Masuda T, Sasano N, and Takahashi T, The size and number of Langerhans islets correlated with their endocrine function: a morphometry on immunostained serial sectioned adult human pancreases, Tohoku J Exp Med 149: 1-10, (1986).
Kawashima Y, Yamamoto H, Takeuchi H and Kuno Y, Mucoadhesive DL--lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin, Pharm Dev Technol 5:77-85 (2000).
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Kikugawa, R., H. Katsuta, et al. (2009). Differentiation of COPAS-sorted non-endocrine pancreatic cells into insulin-positive cells in the mouse. Diabetologia 52(4): 645-52.
Koh A, Senior P, Salam A, Kin T, Imes S, Dinyari P, Malcolm A, Toso C, Nilsson B, Korsgren O, Shapiro AM. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success., Transplantation. 89(4):465-71, (2010).
Krickhahn M, Buhler C, Meyer T, Thiede A, and Ulrichs K, The morphology of islets within the porcine donor pancreas determines the isolation result: successful isolation of pancreatic islets can now be achieved from young market pigs, Cell Transplant 11: 827-838, (2002).
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Mata A, Fleischman AJ, Roy S, Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems, Biomedical Microdevices 7(4): 281-293 (2005),
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O'Sullivan ES, Johnson AS, Omer A, Hollister-Lock J, Bonner-Weir S, Colton CK, Weir GC. (2010) Rat islet cell aggregates are superior to islets for transplantation in microcapsules. Diabetologia 2010 Jan 26. [Epub ahead of print].
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Qi Z, Shen Y, Yanai G, Yang K, Shirouzu Y, Hiura A, Sumi S. The in vivo performance of polyvinyl alcohol macro-encapsulated islets. Biomaterials. 31(14):4026-31, (2010).
Ritz-Laser B, Oberholzer J, Toso C, Brulhart MC, Zakrzewska K, Ris F, Bucher P, Morel P, and Philippe J, Molecular detection of circulating beta-cells after islet transplantation, Diabetes 51: 557-561, (2002).
Scharp DW, Lacy PE, Santiago J, McCullough C, Weide LG, Falqui L, Marchetti P, Gingerich R, Jaffe A, Cryer P, Anderson C, and Flye W, Insulin independence following islet transplantation into patient with Type 1, insulin dependent diabetes mellitus, Diabetes 39: 515-518, (1990).
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Sutherland DE, Gores PF, Farney AC, Wahoff DC, Matas AJ, Dunn DL, Gruessner RW, and Najarian JS, Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota, Am J Surg 166: 456-491, (1993).
Sweet IR, Khalil G, Wallen AR, Steedman M, Schenkman KA, Reems JA, Kahn SE, and Callis JB, Continuous measurement of oxygen consumption by pancreatic islets, Diabetes Technol Ther 4: 661-672, (2002).
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Veriter S, Mergen J, Goebbels RM, Aouassar N, Gregoire C, Jordan B, Leveque P, Gallez B, Gianello P
, Dufrane D. In Vivo Selection of Biocompatible Alginates for Islet Encapsulation and Subcutaneous Transplantation, Tissue Eng Part A. Feb 11, [Epub ahead of print], (2010).
von Mach MA, Schlosser 3, Weiland M, Feilen FJ, Ringel M, Hengstler JG, Weilemann LS, Beyer J, Kann P, and Schneider S, Size of pancreatic islets of Langerhans: a key parameter for viability after cryopreservation, Acta Diabetol 40: 123-129, (2003).
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Claims (22)
- 細胞を培養するための植込可能でない支持体であって、非接着性のディボットされた表面を有し、
前記表面は、実質的に平坦な上面、
前記支持体の表面は、実質的に平坦な上面がエッチングされた複数のディボットを含み、
各ディボットは、内部底面および内部側壁面を含み、
底面は、丸みを帯ており、
各ディボットは、直径100〜200μm、深さ50〜150μmであり、少なくとも膵臓由来の島細胞を直径150μmより大きいネイティブ大型島および直径が125μm未満であるネイティブ小型島から分離して、細胞培養液中の前記ディボット中で培養し、各ディボット内に再凝集島を形成でき、
細胞は個々のディボット中に分布され、細胞はディボット表面に接着せずそこから移動可能である支持体。 - 請求項1記載の支持体を含む、細胞を培養するためのデバイスであって、
前記平坦支持体を保持するための系をさらに含み、
前記系が底面および内部側壁面および内部容積を形成し、前記底および側壁が実質的に液密性であり、細胞および培地が内部容積中に分布される、デバイス。 - 前記細胞が島細胞である請求項1記載の支持体。
- 前記ディボットが直径100μmおよび深さ60μmである請求項1記載の支持体。
- 前記平坦上面がガラス製である請求項1記載の支持体。
- 滅菌性である請求項1記載の支持体。
- 細胞の培養方法であって、
請求項1に記載の支持体に細胞を導入すること、
を含み、
前記支持体を細胞培養条件に曝露する、細胞の培養方法。 - 前記細胞が島細胞であり、そしてデバイスおよび支持培養条件に曝露後に、前記細胞が小型島に再凝集する請求項7記載の細胞の培養方法。
- 前記細胞が20〜150細胞/1ディボットの比率でディボット中に沈下する請求項7記載の細胞の培養方法。
- 前記ディボットが直径100μmおよび深さ60μmである請求項7記載の方法。
- 導入化学物質に対する応答に関して複数の細胞試料を試験するための方法であって、
(a)請求項2に記載のデバイス中で細胞を培養するステップと、
(b)各ディボットに試験化学物質を導入するステップと、
(c)試験化学物質に対する細胞の応答を分析するステップと、
を包含する方法。 - 請求項1に記載の支持体中の細胞培養液中に保持される島の単離集団であって、
すべての島の少なくとも80%は、直径90μmより小さく、前記島が同一細胞培養液中のネイティブの大型島に比して生存するための多くの栄養および酸素を受け取ることができ、
前記島は、同一細胞培養液中のネイティブの小型および大型島に比して高い細胞生存度を有し、
島インスリン産生は、ネイティブ単離島より10倍以上大きいレベルにより特性化される、島の単離集団。 - 球形である請求項12記載の島の単離集団。
- 前記島が膵臓アルファ細胞、膵臓ベータ細胞および膵臓デルタ細胞である請求項12記載の島の単離集団。
- 前記島の少なくとも85%が生存可能である請求項12記載の島の単離集団。
- 全島の少なくとも80%が直径50μm未満である請求項12記載の島の単離集団。
- 前記島の少なくとも50%が直径37μm未満である請求項12記載の島の単離集団。
- 前記島ベータ細胞が、ネイティブ小型島またはネイティブ大型島から単離されるベータ細胞と比較してより多量にインスリンを産生する請求項12記載の島の単離集団。
- 前記島がネイティブ大型島に比して低拡散バリアを有する請求項12記載の島の単離集団。
- 前記細胞が、前記ディボットされた表面および支持培養条件に暴露した後3次元細胞凝集体に凝集する請求項7に記載の細胞の培養方法。
- 前記ディボット間の平均距離が30μm未満である請求項1に記載の支持体。
- 前記支持体表面は個々の細胞を前記表面に接着できる細胞接着分子が存在しない請求項1に記載の支持体。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/798,529 | 2010-04-06 | ||
US12/798,529 US8735154B2 (en) | 2006-10-30 | 2010-04-06 | Templated islet cells and small islet cell clusters for diabetes treatment |
PCT/US2011/030775 WO2011126921A2 (en) | 2010-04-06 | 2011-03-31 | Templated islet cells and small islet cell clusters for diabetes treatment |
Publications (3)
Publication Number | Publication Date |
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JP2013524787A JP2013524787A (ja) | 2013-06-20 |
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EP (1) | EP2555807B9 (ja) |
JP (1) | JP5956422B2 (ja) |
CN (1) | CN102958543B (ja) |
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US8735154B2 (en) * | 2006-10-30 | 2014-05-27 | The University Of Kansas | Templated islet cells and small islet cell clusters for diabetes treatment |
EP2286822A1 (en) | 2009-08-17 | 2011-02-23 | Universiteit Twente | Diabetes treatment |
US8895048B2 (en) | 2010-04-06 | 2014-11-25 | The University Of Kansas | Templated islet cells and small islet cell clusters for diabetes treatment |
JP2014521335A (ja) * | 2011-07-27 | 2014-08-28 | ユニバーシティ オブ カンザス | 糖尿病治療用膵島細胞および小膵島細胞クラスターテンプレート |
DK2838992T3 (en) * | 2012-04-20 | 2018-02-05 | Biolamina Ab | Maintaining differentiated cells with laminins |
WO2014008432A1 (en) * | 2012-07-06 | 2014-01-09 | The Regents Of The University Of California | Cryopreservation of cells inside a macro-encapsulation device |
JP6145257B2 (ja) * | 2012-10-18 | 2017-06-07 | 株式会社クラレ | エストロゲン活性を評価する方法 |
EP2909311B1 (en) * | 2012-10-18 | 2020-10-07 | The University of Kansas | Improved reliability of assays using a multi-divot platform and multi-source, multi-cell type clusters |
WO2014207578A2 (en) | 2013-06-13 | 2014-12-31 | Orgenesis Ltd. | Cell populations, methods of transdifferention and methods of use thereof |
US20160228377A1 (en) * | 2013-09-19 | 2016-08-11 | Beta-Cell Nv | Method for the treatment of diabetes mellitus |
US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
CN115569136A (zh) | 2014-10-21 | 2023-01-06 | 安克生命科学公司 | 人类治疗剂 |
WO2016181220A2 (en) | 2015-05-13 | 2016-11-17 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions and methods of use thereof |
US20160106687A1 (en) | 2014-10-21 | 2016-04-21 | Life Plus, LLC | Human therapeutic agents |
US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
CA3024296A1 (en) | 2016-05-11 | 2017-11-16 | Animal Cell Therapy - Act | Production of a canine beta cell line from an immature pancreas |
US10597639B2 (en) | 2016-10-20 | 2020-03-24 | Washington University | 3D-printed scaffold device for cell transplantation |
US10767164B2 (en) | 2017-03-30 | 2020-09-08 | The Research Foundation For The State University Of New York | Microenvironments for self-assembly of islet organoids from stem cells differentiation |
WO2018207179A1 (en) | 2017-05-08 | 2018-11-15 | Orgenesis Ltd. | Transdifferentiated cell populations and methods of use thereof |
CN110944653A (zh) * | 2017-05-29 | 2020-03-31 | 奥尔吉尼西丝有限公司 | 用于提供细胞替代疗法的组合物和方法 |
WO2019092135A1 (en) | 2017-11-08 | 2019-05-16 | Animal Cell Therapy - Act | Production of canine pancreatic islets from an immature pancreas |
CN111269873A (zh) * | 2018-12-05 | 2020-06-12 | 中国科学院大连化学物理研究所 | 一种基于微坑芯片的3d胰岛细胞血管化微球构建方法 |
CN114870093B (zh) * | 2022-05-07 | 2023-04-07 | 四川大学 | 基于数字光处理的3d打印组织工程胰岛及其制备方法和用途 |
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US20080103606A1 (en) * | 2006-10-30 | 2008-05-01 | Cory Berkland | Templated islet cells and small islet cell clusters for diabetes treatment |
US8735154B2 (en) * | 2006-10-30 | 2014-05-27 | The University Of Kansas | Templated islet cells and small islet cell clusters for diabetes treatment |
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EP2286822A1 (en) | 2009-08-17 | 2011-02-23 | Universiteit Twente | Diabetes treatment |
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WO2011126921A2 (en) | 2011-10-13 |
DK2555807T5 (da) | 2022-01-03 |
CA2795243C (en) | 2019-06-11 |
MX2012011644A (es) | 2013-02-11 |
US20140219997A1 (en) | 2014-08-07 |
BR112012025172B1 (pt) | 2018-08-28 |
EP2555807B9 (en) | 2021-12-08 |
JP2013524787A (ja) | 2013-06-20 |
DK2555807T3 (da) | 2019-11-11 |
CN102958543A (zh) | 2013-03-06 |
US8735154B2 (en) | 2014-05-27 |
US20100233239A1 (en) | 2010-09-16 |
EP2555807A2 (en) | 2013-02-13 |
AU2011238540A1 (en) | 2012-11-29 |
AU2011238540B2 (en) | 2014-12-04 |
WO2011126921A3 (en) | 2012-01-19 |
BR112012025172A2 (pt) | 2017-06-27 |
CA2795243A1 (en) | 2011-10-13 |
EP2555807B1 (en) | 2019-07-31 |
CN102958543B (zh) | 2016-01-13 |
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