CD56 positive human adult pancreatic endocrine progenitor cells

Patent Number: 7,371,576

The quest for a stem cell therapy for diabetes has led to the evaluation of numerous cellular sources ranging from embryonic stem cells, to bone marrow derived stem cells, to mesenchymal stem cells. One interesting method of expanding insulin producing cells is through extraction of pancreatic progenitors from pancreatic tissue and expanding them.

The current patent teaches a method of isolating pancreatic progenitor cells based on expression of the marker CD56. To immunologists, CD56 is classically known as a marker of the natural killer cell. The full name of CD56 is neural cell adhesion molecule (NCAM), and besides its role in adhesion of NK cells to their targets, CD56 has been shown to play a fundamental role in plasticity of neurons, and other activities such as outgrowth and neuron-neuron reorganization. In addition to expression on NK cells and neurons, CD56 is found on skeletal muscles and non-neuronal CNS cells such as glia.

The patent consists of 2 independent claims. The first covers "A method of obtaining a culture of propagating pancreatic cells that exhibit a CD56 protein". The second independent claim covers "A method of producting an aggregate of insulin producing pancreatic cells."

The first set of claims essentially teaches the dissociation of pancreatic tissue, culturing of pancreatic cells so as to allow expression of CD56 on the undifferentiated progenitors, and purification of the CD56 positive cells that are "propagating". The dependent claims cover ways of isolating the CD56 positive cells, either with antibodies to CD56 or with lectins that bind sugars associated with the CD56 molecule. Furthermore, the dependent claims include "differentiation" into an aggregate of insulin producing cells, with methods of differentiation listed including treatment with HGF, KGF, exendin-4, and also culture on collagen IV.

The second set of claims appear similar to the first set with the exception that instead of producting proparaging pancreatic cells, what is produced is "an aggregate of insulin producing cells."

Reading of the Examples section provides detailed information regarding culture conditions and expansion of the CD56 positive pancreatic cells from a 20 year old donor. Additionally, in vivo production of C-peptide in immune deficient mice injected with the ex vivo propagated cells is demonstrated.

View this patent on the USPTO website.