840-P: Proof of Concept of I.P. Administered Neo-Islet (NI) T1DM Biotherapy: Omentum Becomes the New Endocrine Pancreas by Spontaneous Redifferentiation of In Vitro Dedifferentiated Islet Cells

We published that treatment with allogeneic, species specific NIs, organoids of Mesenchymal Stromal Cells (MSCs) and culture expanded islet cells (ICs) functionally cured/improved the diabetic state in NOD mice, insulin dependent pet dogs, and NOD/SCID mice treated with dog or human NIs without requiring antirejection drugs or encapsulation devices (see also abstract this meeting) . Fig 1 summarizes the mode of action of NI therapy and experimental detail: Dedifferentiated ICs (∼ 6 PDLs) are incorporated into NIs and implanted into diabetic animals. They redifferentiate in vivo and normalize blood glucose levels as demonstrated by gene expression analysis on NIs retrieved from euglycemic diabetic mice at 21 weeks post administration. As seen in the right portion of the graph, gene expression levels of islet endocrine hormones in retrieved NIs are not significantly different from those of freshly isolated islets (log10 (RQ) < ± 2) . These data demonstrate that although culture expansion of islet cells decreases endocrine gene expression as a function of PDLs, incorporation of ICs into NIs and implantation into a diabetic subject results in redifferentiation of the ICs, reestablishment of euglycemia, and restoration of islet hormone gene expression.