Capture of endothelial progenitor cells by a bispecific protein/monoclonal antibody molecule induces reendothelialization of vascular lesions

Abstract

Tissue injury is inevitably accompanied by disruption of the endothelium and exposure of the subendothelial matrix. To generate a guidance molecule directing progenitor cells to sites of vascular lesions, we designed a bifunctional protein. The protein consists of the soluble platelet collagen receptor glycoprotein VI and an antibody to CD133 (hereafter called GPVI-CD133). In vitro and in vivo, this construct substantially mediates endothelial progenitor cell (EPC) homing to vascular lesions. Exposure of EPCs to GPVI-CD133 did not impair their capability to differentiate toward mature endothelial cells as verified by the formation of colony-forming units, the upregulation of endothelial markers CD31 and CD146 analyzed by flow cytometry or von Willebrand factor and endoglin assessed by immunofluorescence microscopy, as well as the presence of Weibel-Palade bodies using transmission electron microscopy. In vivo, GPVI-CD133 augments reendothelialization of vascular lesions. Thus, this bifunctional protein could be a potential new therapeutic option for cardiovascular diseases.

Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting

“…MagBICE and bispecific T-cell engager are similar in that both exploit conjoined antibodies to achieve molecular co-localization. Bispecific proteins and antibodies have also been used to enhance stem cell targeting and tissue regeneration16171819. MagBICE, however, differs fundamentally from bispecific antibodies in that the iron core enables visualization of tissue localization by MRI and enhancement of targeting efficacy by local magnetic fields.…”

Sandwich Immunoassay for Soluble Glycoprotein VI in Patients with Symptomatic Coronary Artery Disease

“…To date, a cooperative study has performed studies on this therapeutic principle and accomplished a phase I study that examined safety and pharmacokinetic and -dynamic profiles of an sGPVI called Revacept® in healthy volunteers in a single-center, open-label, dose-escalating study with 5 doses (28 ). Furthermore, a specially designed bifunctional protein of sGPVI may catch progenitor cells to induce reendothelialization of vascular lesions (29 ).…”

Current concepts and new developments for autologous in vivo endothelialisation of biomaterials for intravascular applications

“…CFU-EC colonies appear within 4-7 days of culture as discrete colonies comprising round cells in the centre and spindle-shaped cells sprouting at the periphery (Hill et al, 2003). "Late" EPCs can be obtained using the cultivation method reported by Lin and Ingram (Ingram et al, 2004;Lin et al, 2000). MNCs are incubated on collagen I-coated plates in endothelial specific growth medium.…”

“…Recently, a promising new concept for further modification of EPC specific capture molecules was developed by Langer and colleagues to guide the captured EPCs to vascular lesions (Langer et al, 2010). A bispecific molecule (called GPVI-CD133 construct) was designed, consisting of a recombinant form of the soluble platelet collagen receptor glycoprotein VI (GPVI) targeting collagen, which is the main component of the injured vessel wall, and a monoclonal antibody targeting CD133 on EPCs.…”