Date: Monday, June 3, 2019
Session Name: Concurrent Session: Islet and Cell Transplantation
Session Time: 4:30pm-6:00pm
Presentation Time: 4:54pm-5:06pm
Location: Room 309
*Purpose: Islet transplantation can cure Type 1 diabetes; however, multiple donors are needed due to extensive perioperative loss of islets when removed from their native blood supply. We recently discovered that CD34+45- vascular endothelial cells from parathyroid glands (PTG), another richly vascular endocrine organ, have an extraordinary ability to promote beta cell engraftment and function. This study aimed to generate a human embryonic stem-cell (hESC) derived source of CD34+45- vascular endothelial cells that could equitably protect islet grafts.
*Methods: hESC-derived β-cells (eBCs) and CD34+45- (scCD34+) cells were differentiated from the same stem cell line and were co-transplanted in the subcutaneous (SQ) and intramuscular (IM) sites of immunodeficient mice. scCD34+ cells were FACS purified.
*Results: Using the same hESC line that we have used to produce eBCs, we have succeeded in generating CD34+CD45- cells after 9 days of in-vitro differentiation. These scCD34+ cells lack the hematopoietic marker CD45 and contain the endothelial precursor marker CD146+ (Fig A). Moreover, these cells efficiently formed tubular structures in 4 hours in an in vitro angiogenesis assay, suggesting that these cells are vascular endothelial progenitor cells (Fig B). Transplantation of scCD34+ cells in an in-vivo angiogenesis model, using mouse skin flaps, resulted in increased vascular density and number of vessel junctions compared to sham and hematopoietic CD34+45+ cells differentiated simultaneously. Co-transplantation of scCD34+ with eBCs in SQ and IM sites resulted in significant improvement of graft mass preservation when compared with eBC transplanted alone. Moreover, we developed a novel co-clustering method to combine scCD34+ with eBCs prior to transplantation, creating vascularized beta cells, which showed further engraftment protection in the SQ and IM via luciferase imaging when compared to control.
*Conclusions: While the βετα-cell-protective activity of PTG CD34+ cells is remarkable, a renewable source of CD34+ cells that possess the same activities of PTG CD34+ cells is highly desired to enable wide application of βετα-cell replacement therapy. This study show that vascular progenitor cells can be generated from stem cells and used to support the engraftment of stem cell derived beta cells.
To cite this abstract in AMA style:Ward C, Vo L, Klerk EDe, Faleo G, Kelly Y, Bluestone J, Hebrok M, Stock P, Tang Q. Preservation of Pancreatic Islets with Stem Cell Derived CD34+ Vascular Endothelial Progenitor Cells [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/preservation-of-pancreatic-islets-with-stem-cell-derived-cd34-vascular-endothelial-progenitor-cells/. Accessed September 24, 2020.
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