Composition and methods for producing insulin producing islet cells

Inventors

THAI, NGOC • POLLETT, JONATHAN

Assignees

Imagine Pharma LLC

Abstract

Disclosed herein are compositions and methods to differentiate pancreatic cells into functional insulin-producing CD133/Ki-67-positive activated islet proliferating cells (AIPCs) derived from isolated pancreatic islets and expand derived-AIPCs in in vitro cultures using a culture medium comprising an active agent. Also disclosed herein is the use of the AIPCs for implantation into a mammal for in vivo therapy, specifically for pancreatic disorders, including diabetes type I.

Core Innovation

The invention relates to generating and expanding an activated islet proliferating cell (AIPC) population from isolated pancreatic islets by culturing a population of pancreatic islets in vitro with a cell culture medium comprising a base medium and a polypeptide according to the amino acid sequence of SEQ ID NO: 1 to obtain the AIPC population. The disclosed polypeptide may also be used as fragments corresponding to SEQ ID NOs 2-4, with sequence-identity scope described in the document.

The resulting AIPC population is defined by cell marker positivity and insulin production capability. In particular, at least 60% of the AIPC population comprises CD133 and Ki-67 cell marker positivity, and at least 60% of the AIPC population is capable of insulin production. Additional described embodiments further characterize a triple positive phenotype with insulin, CD133, and Ki-67 positivity.

The document further describes functional behaviors and in vivo performance of the AIPC population. The AIPCs are described as glucose-responsive with insulin secretion and ability to migrate out of islet clusters and form colonies, and histology indicates donor cell division (Ki-67+ donor cells) in the pancreas after engraftment/homing. The document additionally outlines treatment and implantation concepts, including encapsulated formulations, for pancreatic disorders such as type 1 diabetes.

Claims Coverage

The document provides one independent claim that defines the method of generating an activated islet proliferating cell (AIPC) population. The independent claim includes three core inventive elements: in vitro culturing of pancreatic islets with a base medium and a SEQ ID NO: 1 polypeptide, marker/threshold criteria for CD133 and Ki-67, and functional threshold criteria for insulin production capability.

Overall, the claim coverage centers on the generation of an AIPC population by in vitro culturing pancreatic islets with a base medium containing a SEQ ID NO: 1 polypeptide, followed by defining the resulting population by CD133 and Ki-67 marker positivity thresholds and by a functional insulin production capability threshold.

Stated Advantages

Documented Applications