The recombinant bifunctional protein αCD133–GPVI promotes repair of the infarcted myocardium in mice

Baumer, Yvonne; Leder, Christoph; Ziegler, Melanie; Schönberger, Tanja; Ochmann, Carmen; Perk, Aliye Aras; Degen, Heidrun; Schmid-Horch, Barbara D.; Elvers, Margitta; Münch, Götz; Ungerer, Martin; Schlosshauer, Bürkhard; Gawaz, Meinrad

doi:10.1111/j.1538-7836.2012.04710.x

Cited by 12 publications

(7 citation statements)

References 53 publications

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“…PIM-1, a pro-survival and proliferation gene kinase, has been used to enhance CPCs with demonstrated long-term engraftment, increased cardiac function and reduced fibrotic scar as compared to regular CPCs or placebo in both small [130] and large animal models [132]. On a molecular level, a bi-functional genetically engineered fusion protein can be created to augment engraftment and binding of the functional stem cell(s) to damaged tissue, such as modification of αCD133-GPVI to bind CD133+ progenitor cells to damaged vessels producing higher capillary density and tissue vascularization [137]. Through a variety of approaches, the use of genetic modification provides a means to amplify and enhance traits associated with therapeutic success.…”

Section: Current Status Of Adult Stem Cell Therapiesmentioning

confidence: 99%

Empowering Adult Stem Cells for Myocardial Regeneration V2.0

Broughton

Sussman

2016

Circulation Research

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Much has changed since our survey of the landscape for myocardial regeneration powered by adult stem cells four years ago (Mohsin et al., Empowering adult stem cells for myocardial regeneration. Circ Res. 2011; 109(12):1415–1428) [1]. The intervening years since that first review has witnessed an explosive expansion of studies that advance both understanding and implementation of adult stem cells in promoting myocardial repair. Painstaking research from innumerable laboratories throughout the world is prying open doors that may lead to restoration of myocardial structure and function in the wake of pathologic injury. This global effort has produced deeper mechanistic comprehension coupled with an evolving appreciation for the complexity of myocardial regeneration in the adult context. Undaunted by both known and (as yet) unknown challenges, pursuit of myocardial regenerative medicine mediated by adult stem cell therapy has gathered momentum fueled by tantalizing clues and visionary goals. This concise review takes a somewhat different perspective than our initial treatise, taking stock of the business sector that has become an integral part of the field while concurrently updating “state of affairs” in cutting edge research. Looking retrospectively at advancement over the years as all reviews eventually must, the fundamental lesson to be learned is best explained by Jonatan Mårtensson: “Success will never be a big step in the future. Success is a small step taken just now.”

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Section: Current Status Of Adult Stem Cell Therapiesmentioning

confidence: 99%

Empowering Adult Stem Cells for Myocardial Regeneration V2.0

Broughton

Sussman

2016

Circulation Research

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“…The controversial aspects of CD34 for cell capture are outlined above. CD133 is evident on EPCs localized in the bone marrow and has been integrated into chimeric proteins together with the collagen‐binding protein GPVI in order to recruit EPCs to traumatized vascular sites (Baumer et al ., ). However, circulating EPCs appear to downregulate CD133 (Hristov et al ., ) and thus significantly decrease the homing via this antigen.…”

Section: Discussionmentioning

confidence: 97%

Towards a biofunctionalized vascular prosthesis: immune cell trapping via a growth factor receptor

Liebler

Fritz²,

Thompson³

et al. 2016

J Tissue Eng Regen Med

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To improve the clinical performance of vascular prostheses, which is inacceptably low for implants with small diameters (< 6 mm), biofunctionalization of synthetic implants by endothelialization has become a major, although still unreached, aim. In order to be able to recruit native endothelial progenitor cells (EPCs) to luminal implant surfaces from the blood stream, we generated monoclonal antibodies against the EPC-specific vascular endothelial growth factor receptor 2 (VEGFR-2). Employing the very efficient genetic immunization strategy, > 10 000 hybridoma clones were generated. Screening with various deletion mutants of VEGFR-2, 49 highly-specific monoclonal antibodies (mAbs) covering all seven Ig domains of VEGFR-2 were selected. mAb 9H10 was characterized in detail. Once immobilized on synthetic surfaces, mAb 9H10 allowed, within min, nearly 100-fold enrichment of VEGFR-2-expressing cells under continuous flow conditions. Cell trapping was cell-type specific and essentially not affected by competing VEGFR-2-negative cells. To exclude that the antibody would adversely modify receptor responses, four different in vitro assays were employed. Cell proliferation, angiogenic tube formation, acetylated low-density lipoprotein uptake and VEGFR-2 phosphorylation remained unaffected, suggesting that the antibody did not interfere with the receptor functioning of human umbilical vascular endothelial cells. The molecular and cellular characteristics make the selected monoclonal antibody a very promising tool for the biofunctionalization of vascular implants. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Mice were anaesthetized 24 h after surgery and the ischemic and infarcted area was estimated by Evans Blue/triphenyltetrazolium chloride (TTC) staining as described previously4748. Briefly, the LAD was re-ligated with the same suture and 4% Evans Blue (AppliChem) was injected as a negative staining for perfused regions.…”

Section: Methodsmentioning

confidence: 99%

Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets

Ziegler

Alt

Paterson

et al. 2016

Sci Rep

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A reliable method for the diagnosis of minimal cardiac ischemia would meet a strong demand for the sensitive diagnosis of coronary artery disease in cardiac stress testing and risk stratification in patients with chest pain but unremarkable ECGs and biomarkers. We hypothesized that platelets accumulate early on in ischemic myocardium and a newly developed technology of non-invasive molecular PET imaging of activated platelets can thus detect minimal degrees of myocardial ischemia. To induce different degrees of minimal cardiac ischemia, the left anterior descending artery (LAD) was ligated for 10, 20 or 60 min. Mice were injected with a newly generated scFvanti-GPIIb/IIIa-64CuMeCOSar radiotracer, composed of a single-chain antibody that only binds to activated integrin GPIIb/IIIa (αIIbβIII) and thus to activated platelets, and a sarcophagine cage MeCOSar complexing the long half-life PET tracer copper-64. A single PET/CT scan was performed. Evans Blue/TTC staining to detect necrosis as well as classical serological biomarkers like Troponin I and heart-type fatty acid-binding protein (H-FABP) were negative, whereas PET imaging of activated platelets was able to detect small degrees of ischemia. Taken together, molecular PET imaging of activated platelets represents a unique and highly sensitive method to detect minimal cardiac ischemia.

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The recombinant bifunctional protein αCD133–GPVI promotes repair of the infarcted myocardium in mice

Cited by 12 publications

References 53 publications

Empowering Adult Stem Cells for Myocardial Regeneration V2.0

Empowering Adult Stem Cells for Myocardial Regeneration V2.0

Towards a biofunctionalized vascular prosthesis: immune cell trapping via a growth factor receptor

Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets

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