"Steering Stem Cells to Treat Osteoporosis"
Robert
Sackstein, MD, PhD, Associate Professor of
Dermatology and of Medicine, Harvard Medical School; Head of the Translational
Research Program of the Bone Marrow Transplantation Unit,
Moderator:
Charles A. Vacanti, MD. Anesthesiologist-in-Chief, Leroy D.
Vandam/Benjamin G. Covino, Professor of Anaesthesia,
The successful clinical implementation of stem cell-based regenerative therapeutics depends critically on the ability to deliver stem cells to sites where they are needed. CD44 is a transmembrane glycoprotein that is expressed at high levels on most stem/progenitor cells. A specialized glycoform of CD44 called "Hematopoietic Cell E-/L-selectin Ligand" (HCELL) is a potent E-selectin ligand. E-selectin is an endothelial molecule that is expressed constitutively on the luminal surface of bone marrow microvascular endothelium, and is also found on post-capillary venules at all sites of tissue injury. E-selectin receptor/ligand interactions mediate shear-resistant adhesive interactions between cells in blood flow and endothelium, the critical first step in recruitment of circulating cells to any target tissue. Robert Sackstein's lab has developed a platform technology called "Glycosyltransferase-Programmed Stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells. Ex vivo glycan engineering of CD44 via GPS licenses osteotropism of human MSC to the bone, where these cells differentiate into osteoblasts and produce human osteoid in a NOD/SCID xenotransplant model. GPS technology thus has profound implications in therapy of generalized bone diseases such as osteoporosis, and may also be exploited for stem-cell based regenerative therapeutics for non-skeletal diseases.
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