Biomimicry and Regenerative
Therapeutics
4:00PM Biomimicry
- Nature as Model, Measure and Mentor
Jeffrey Karp, PhD, Instructor in Medicine
and Health Sciences and Technology, Harvard Medical School, Brigham and Women's
Hospital; Director, Laboratory for Advanced Biomaterials and
Stem-Cell-Based Therapeutics, BWH, jmkarp@partners.org
Moderator:
Frederick J. Schoen, MD, PhD, Professor of Pathology and Health
Sciences and Technology, Harvard Medical School; Director of Cardiac Pathology
and Executive Vice-Chairman,Department of Pathology, Brigham and Women’s
Hospital, CIMIT Site Miner, BWH, fschoen@partners.org
Evolved
designs in nature offer opportunities for biomedical engineering. Jeffrey Karp
will explain two biomimetic approaches currently employed. The first is in the
field of biomedical adhesives using nano and microscale approaches, based on
the understanding gecko mobility. Geckos attach to smooth vertical surfaces and
support their weight with a single toe. The mechanism of this biological phenomenon
was recently elucidated; nearly two millennia after Aristotle first reported
it. The second is creating materials to capture cells mimicking the vascular
endothelium’s ability to initiate cell rolling in viscous shear flow. Surface
engineering through covalent immobilization of selectins can achieve long term
precise control over cell rolling, which may be useful for capturing and
separating cells for diagnostic and therapeutic applications.
4:50PM 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, Massachusetts General
Hospital and the Dana-Farber Cancer Institute, rsackstein@partners.org
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.