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Sc-beta cells and compositions and methods for generating the same

a technology applied in the field of scbeta cells and compositions and methods for generating the same, can solve the problems that the hpsc-derived insulin-expressing cells generated by existing methods fail to secrete insulin appropriately in response to the addition of various substances

Inactive Publication Date: 2017-02-02
JANSSEN BIOTECH INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention describes methods to create pancreatic β cells that can produce and secrete insulin. These cells can be used for transplant therapy, drug screening, and research. These cells also have the potential to be used as a platform for tissue engineering. The technical effects of this invention are the creation of a new tool for research and potential treatment of diabetes.

Problems solved by technology

In contrast to normal islets or dispersed adult β cells, which release high levels of insulin in response to high levels of glucose in the “glucose stimulated insulin secretion” (GSIS) assay and can do so repeatedly, hPSC-derived insulin-expressing cells generated by existing methods fail to secrete insulin appropriately in response to the addition of various concentrations of glucose.

Method used

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  • Sc-beta cells and compositions and methods for generating the same
  • Sc-beta cells and compositions and methods for generating the same
  • Sc-beta cells and compositions and methods for generating the same

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Generation of Functional Pancreatic β Cells In Vitro

[0584]Summary

[0585]The generation of insulin-producing pancreatic β cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many characteristics of bona fide β cells including function in vitro and / or in vivo. The work described herein demonstrates an exemplary scalable differentiation protocol that generates SC-β cells from hPSC in vitro. Surprisingly, and unexpectedly, these SC-β cells secrete amounts of insulin comparable to adult β cells in response to multiple sequential glucose challenges, flux Ca2+, express markers found in β cells, and package insulin into secretary granules. As a proof of concept, SC-β cells also respond to known diabetes drugs and proliferative cues in vitro. Furthermore, the SC-β cells secrete high levels of human insulin in...

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Abstract

Disclosed herein are methods, compositions, kits, and agents useful for inducing β cell maturation, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 833,898, filed on Jun. 11, 2013, and U.S. Provisional Application No. 61 / 972,212, filed on Mar. 28, 2014, the contents of which are hereby incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]Research to-date has generated only abnormally functioning insulin-expressing cells, which do not secrete appropriate amounts of insulin in response to sequentially varied glucose levels, or pancreatic progenitor cells that can only mature into functioning insulin-expressing cells after 3 months of transplantation into a mouse host (Cheng et, al., 2012; D′Amour et al., 2005; D′Amour et al., 2006; Kroon et al., 2008; Nostro et al., 2011; Rezania et al., 2012; Schulz et al., 2012; Xie et al., 2013). In contrast to normal islets or dispersed adult β cells, which release high levels of insulin in response to high levels of glucose in the “glucose stimulated...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N5/071
CPCC12N5/0678C12N2501/727C12N2501/395C12N2501/998C12N2501/11C12N2501/41C12N2501/385C12N2506/22C12N2501/15C12N2501/117C12N2501/16C12N2501/999C12N2506/02C12N2506/45C12N5/0606C12N5/0696C12N2501/375C12N5/0676A61P5/48A61P5/50A61P3/10A61K35/39C12N2501/40C12N2500/38C12N2506/03
Inventor PETERSON, QUINN P.PAGLIUCA, FELICIA J.MELTON, DOUGLAS A.MILLMAN, JEFFREY R.SEGEL, MICHAEL SARISGURTLER, MADSREZANIA, ALIREZAFRYER, BENJAMIN
Owner JANSSEN BIOTECH INC
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