Tissue Engraftment Research Articles

Abstract 560: Surface Glycoengineering of Mesenchymal Stem Cells and Cardiosphere-Derived Cells Enhances Selectin-Mediated Cell Rolling and Tethering

Background: Of the current stem cell delivery routes, vascular injection has the advantage of not being limited by the poor vascular accessibility of the donor cells as in the cases of intramyocardial injection and cell-sheet placement. However, there is concern about the lower cell retention in the heart; thus, we access the hypothesis that modifying the cell surface glycosylation on MSCs and CDCs can enhance their interaction to inflammatory sites by increasing interactions with endothelial selectins. Methods: Two approaches were taken to address the hypothesis. First, the non-covalent coupling of a P-selectin glycoprotein ligand-1 (PSGL-1) fusion protein called 19Fc[FUT7 + ] to MSCs and CDCs is performed using two types of protein G lipid conjugates, either PPG or DPG. Second, we investigated the increased of α(1,3) fucose on the cell surface glycans by overexpression of three fucosyltransferases (FUT6, FUT7, and FUT9). Results: MSCs functionalized with 19Fc[FUT7 + ] were captured onto stimulated endothelial cell monolayers at wall shear stresses up to 4 dyn/cm 2 . Both MSCs and CDCs could be captured onto P-selectin substrates up to 6 dyn/cm 2 , (Table 1). In the case of fucosyltransferase overexpression, FUT7 improved the number of both MSCs and CDCs captured onto P- and E-selectin substrates. FUT9 also significantly improved the number of CDCs captured to E-selectin. Conclusion: The current work presents a robust strategy for enabling leukocyte-like capture and rolling under constant flow conditions to enhance cell delivery efficiency thereby increasing tissue engraftment. This method could be employed to increase tissue engraftment of cells used in stem cell therapy.

Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2−/−γc−/−CD47−/− background

C57BL/6 Rag2−/−γc−/−CD47−/− triple-knockout mice engrafted with fetal human bone marrow, liver, thymus (TKO-BLT) not only develop high levels of multi-lineage hematopoiesis but also organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissues of human origin. A unique advantage of these mice is that they sustain human cell and tissue engraftment long-term without the development of graft versus host disease. Thus they can be used for long-term studies not previously feasible with other models. The production of TKO-BLT mice to obtain healthy mice with high level reconstitution of human cells and tissues requires specialized methods that are presented in detail.

Wnt7a stimulates myogenic stem cell motility and engraftment resulting in improved muscle strength

Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse satellite cells and human myogenic progenitors through activation of Dvl2 and the small GTPase Rac1. Importantly, these effects can be exploited to potentiate the outcome of myogenic cell transplantation into dystrophic muscles. We observed that a short Wnt7a treatment markedly stimulated tissue dispersal and engraftment, leading to significantly improved muscle function. Moreover, myofibers at distal sites that fused with Wnt7a-treated cells were hypertrophic, suggesting that the transplanted cells deliver activated Wnt7a/Fzd7 signaling complexes to recipient myofibers. Taken together, we describe a viable and effective ex vivo cell modulation process that profoundly enhances the efficacy of stem cell therapy for skeletal muscle.

Histopathological characteristics of human non-tumor thyroid tissues in a long-term model of adenomatous goiter xenografts in the NOD/Shi-scid, IL-2Rγnull mouse

There is a growing need for modeling the human thyroid to link data obtained from animals to humans because of its sensitivity to radiation exposure and endocrine disruption chemicals. In a scid mouse model produced by transplanting human thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the scid mouse can complicate the interpretation of experimental results. Considering that the NOD.Cg-PrkdcscidIl2rgtm1Sug/Jic mouse (NOD/Shi-scid, IL-2Rγnull or NOG mouse) may be a better host because this strain has low incidence of leakiness and thymic lymphoma, we have evaluated the potential of a model that allows long-term observation of non-tumor human thyroid tissues in this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and examined the tissues histopathologically. The morphology of human adenomatous goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG mice with no noted differences between donor-matched tissues or the weeks after transplantation. The tissues expressed thyroglobulin protein and mRNA as well as thyroperoxidase. Endothelial cells originating from human were found in the transplanted tissues and were thought to be a characteristic of this model. The intactness of the tissues before transplantation was found to affect the rate of tissue engraftment. From the present results we have concluded that transplanted thyroid tissues in NOG mice maintain the histopathological characteristics of their origin for long terms. Therefore this model was thought feasible for toxicity evaluation.

The Effect of Projection Microstereolithographic Fabricated Implant Geometry on Myocutaneous Revascularization

Understanding cell behavior inside three-dimensional (3D) microenvironments with controlled spatial patterning of physical and biochemical factors could provide insight into the basic biology of tissue engraftment, vascular anastomosis, and revascularization. A simple layer by layer projection microstereolithography (PμSL) method was utilized to investigate the effects of a nonporous and porous bioinert barrier on myocutaneous flap engraftment and revascularization. A cranial-based, peninsular-shaped myocutaneous flap was surgically created on the dorsum of C57Bl6 mice. Porous (SP) and nonporous (S) silicone implants were tailored to precise flap dimensions and inserted between the flap and recipient bed prior to sutured wound closure. Porous implant myocutaneous flaps became engrafted to the recipient site with complete viability. In contrast, distal cutaneous necrosis and resultant flap dehiscence was evident by day 10 in nonporous implant flap mice. Laser speckle contrast imaging demonstrated flap revascularization in (SP) mice, and markedly reduced distal flap reperfusion in (S) mice. Histologic analysis of day 10 (SP) flaps revealed granulation tissue rich in blood vessels and macrophages growing through the implant pores and robust neovascularization of the distal flap. In contrast, the nonporous implant prevented tissue communication between recipient bed and flap with lack of bridging inflammatory cells and neovasculature and resultant distal tissue necrosis. We have fabricated porous and nonporous silicone implants via a simple and inexpensive technique of PμSL. Using a graded-ischemia wound healing model, we have shown that porous implants allowed contact between flap and recipient bed resulting in proximal flap arteriogenesis and neovascularization of the distal flap. Future research will utilize variations in implant pore size, spacing, and location to gain a better understanding of the cellular and molecular mechanisms responsible for myocutaneous flap engraftment, vascular anastomosis, and revascularization.

The Effect of Projection Microstereolithographic Fabricated Implant Geometry on Myocutaneous Revascularization

Understanding cell behavior inside three-dimensional (3D) microenvironments with controlled spatial patterning of physical and biochemical factors could provide insight into the basic biology of tissue engraftment, vascular anastomosis, and revascularization. A simple layer by layer projection microstereolithography (PμSL) method was utilized to investigate the effects of a nonporous and porous bioinert barrier on myocutaneous flap engraftment and revascularization. A cranial-based, peninsular-shaped myocutaneous flap was surgically created on the dorsum of C57Bl6 mice. Porous (SP) and nonporous (S) silicone implants were tailored to precise flap dimensions and inserted between the flap and recipient bed prior to sutured wound closure. Porous implant myocutaneous flaps became engrafted to the recipient site with complete viability. In contrast, distal cutaneous necrosis and resultant flap dehiscence was evident by day 10 in nonporous implant flap mice. Laser speckle contrast imaging demonstrated flap revascularization in (SP) mice, and markedly reduced distal flap reperfusion in (S) mice. Histologic analysis of day 10 (SP) flaps revealed granulation tissue rich in blood vessels and macrophages growing through the implant pores and robust neovascularization of the distal flap. In contrast, the nonporous implant prevented tissue communication between recipient bed and flap with lack of bridging inflammatory cells and neovasculature and resultant distal tissue necrosis. We have fabricated porous and nonporous silicone implants via a simple and inexpensive technique of PμSL. Using a graded-ischemia wound healing model, we have shown that porous implants allowed contact between flap and recipient bed resulting in proximal flap arteriogenesis and neovascularization of the distal flap. Future research will utilize variations in implant pore size, spacing, and location to gain a better understanding of the cellular and molecular mechanisms responsible for myocutaneous flap engraftment, vascular anastomosis, and revascularization.

Concise Review: Engineering Myocardial Tissue: The Convergence of Stem Cells Biology and Tissue Engineering Technology

Abstract Advanced heart failure represents a leading public health problem in the developed world. The clinical syndrome results from the loss of viable and/or fully functional myocardial tissue. Designing new approaches to augment the number of functioning human cardiac muscle cells in the failing heart serve as the foundation of modern regenerative cardiovascular medicine. A number of clinical trials have been performed in an attempt to increase the number of functional myocardial cells by the transplantation of a diverse group of stem or progenitor cells. Although there are some encouraging suggestions of a small early therapeutic benefit, to date, no evidence for robust cell or tissue engraftment has been shown, emphasizing the need for new approaches. Clinically meaningful cardiac regeneration requires the identification of the optimum cardiogenic cell types and their assembly into mature myocardial tissue that is functionally and electrically coupled to the native myocardium. We here review recent advances in stem cell biology and tissue engineering and describe how the convergence of these two fields may yield novel approaches for cardiac regeneration. Stem Cells 2013;31:2587–2598

Humanized NOD-SCID IL2rg–/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies

Humanized mouse models have been developed and utilized in cancer research for decades. Newly developed combined immunodeficient NOD-SCID-IL2rg–/– mice are more permissive for human cells and tissue engraftment. In this review, we discuss the use of NOD-SCID-IL2rg–/– mice as a preclinical tool in cancer research and its potential use for individualized cancer therapies.

Autologous Pancreatic Islet Transplantation in Human Bone Marrow

The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans.

The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling

Mesenchymal stem/stromal cells (MSCs) are an important candidate for cell-based therapy since they can be easily isolated and expanded, secrete beneficial paracrine factors, and differentiate into multiple lineages. Since the endothelium at sites of injury and inflammation often express adhesion molecules belonging to the selectin family, methods to endow MSCs with selectin-ligands can enhance the efficacy of cell delivery and tissue engraftment. Here, we describe a construct 19Fc[FUT7+], where the first 19 amino acids of the pan-selectin ligand PSGL-1 (P-selectin glycoprotein ligand-1) was fused to a human IgG1. When expressed in HEK293T cells over-expressing the α(1,3)fucosyltransferase FUT7, 19Fc[FUT7+] is decorated by a core-2 sialyl Lewis-X sialofucosylated O-glycan. The non-covalent coupling of this protein onto MSC surface using palmitated protein G (PPG) enhanced cell binding to E- and P-selectin under hydrodynamic shear, without altering MSC multipotency. MSCs functionalized with 19Fc[FUT7+] were captured/tethered onto stimulated endothelial cell monolayers at wall shear stresses up to 4 dyn/cm2. Once captured, the cells rolled robustly up to the highest shear stress tested, 10 dyn/cm2. Unlike previous work where MSCs could only be captured onto selectin-bearing substrates at low or no-flow conditions, the current work presents a ‘glycan engineering’ strategy to enable leukocyte-like capture and rolling.

Mo1986 Vasoactive Intestinal Peptide (VIP) Plays a Role in the Regulation of Orexigenic and Anorexigenic Hormones and Body Fat and Lean Mass Composition

Aim: To create HEK293 cells and murine ES cell lines that synthesize and release either GIP or the specific GIPR antagonist GIP(5-42). Methods: Using PCR, chimeric genes, consisting of the mouse growth hormone leader (mGH), the furin cleavage site, and either GIP or GIP(5-42), were generated and cloned into a lentiviral vector downstream of a constitutive promoter. After the generation of lentiviral pseudoparticles containing the chimeric genes, mGH-GIP and mGH-GIP(5-42), HEK 293 and ES cells were transduced with ~108 pseudoparticles. Pools of cells containing the co-expressed fluorescent marker ZsGreen were isolated using flow cytometry before supernates from cultured cells were collected, and a specific ELISA was employed to quantify GIP immunoreactivity. To assess GIP bioactivity in supernates, a specific bioassay consisting of reporter cells expressing GIPR and containing the LacZ gene under the control of a cAMP-responsive promoter was used. To demonstrate antagonist activity, peptides in supernates from HEK 293 cells containing mGH-GIP(5-42) were concentrated 50-fold using a C-18 reverse phase column before being mixed with 1010 M GIP and added to reporter cells. Results: HEK 293 cells containing mGH-GIP and mGH-GIP(5-42) expressed 8x10-4 and 10-4 pg/cell/h, respectively, while ES cells containing mGH-GIP and mGH-GIP(5-42) expressed 10-4 and 6x10-3 pg/cell/h, respectively. Supernates from HEK 293 and ES cells containing mGH-GIP were both shown to induce LacZ expression, demonstrating the presence of bioactive GIP. As expected, supernates from either HEK 293 cells or ES cells containing mGH-GIP(5-42) did not induce LacZ expression. However, after concentration, supernates from HEK 293 cells containing mGH-GIP(5-42) inhibited LacZ expression induced by 10-10 M GIP, indicating the presence of antagonist activity. Summary and Conclusion: The results of these studies demonstrate the successful engineering of HEK 293 and ES cells to express bioactive GIP and GIP(5-42). Although early in its development, engraftment of tissue derived fromGIP(5-42) expressing stem cells may provide a method for treating obesity.

Establishment of a Novel dsRed NOD/Scid Mouse Strain to Investigate the Host and Tumor Cell Compartments

Here we describe a NOD/Scid mouse strain expressing the dsRed transgene. The strain is maintained by inbreeding of homozygous dsRed NOD/Scid siblings, and expresses red fluorescence from various organs. The model allows engraftment of human tumor tissue, and engrafted tumors were separated into stromal and malignant cell compartments. Furthermore, we compared tumor-associated and normal fibroblast for expression of fibroblast-associated markers, and identified a marker panel that was upregulated in the tumor-associated fibroblasts. In conclusion, we propose that this model may be used in a variety of studies of tumor progression and to elucidate the role of the tumor microenvironment.

Tissue engraftment of hypoxic‐preconditioned adipose‐derived stem cells improves flap viability

Adipose-derived stem cells (ASCs) have the ability to release multiple growth factors in response to hypoxia. In this study, we investigated the potential of ASCs to prevent tissue ischemia. We found conditioned media from hypoxic ASCs had increased levels of vascular endothelial growth factor (VEGF) and enhanced endothelial cell tubule formation. To investigate the effect of injecting rat ASCs into ischemic flaps, 21 Lewis rats were divided into three groups: control, normal oxygen ASCs (10(6) cells), and hypoxic preconditioned ASCs (10(6) cells). At the time of flap elevation, the distal third of the flap was injected with the treatment group. At 7 days post flap elevation, flap viability was significantly improved with injection of hypoxic preconditioned ASCs. Cluster of differentiation-31-positive cells were more abundant along the margins of flaps injected with ASCs. Fluorescent labeled ASCs localized aside blood vessels or throughout the tissue, dependent on oxygen preconditioning status. Next, we evaluated the effect of hypoxic preconditioning on ASC migration and chemotaxis. Hypoxia did not affect ASC migration on scratch assay or chemotaxis to collagen and laminin. Thus, hypoxic preconditioning of injected ASCs improves flap viability likely through the effects of VEGF release. These effects are modest and represent the limitations of cellular and growth factor-induced angiogenesis in the acute setting of ischemia.

Trophic Actions of Bone Marrow-Derived Mesenchymal Stromal Cells for Muscle Repair/Regeneration

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent the leading candidate cell in tissue engineering and regenerative medicine. These cells can be easily isolated, expanded in vitro and are capable of providing significant functional benefits after implantation in the damaged muscle tissues. Despite their plasticity, the participation of BM-MSCs to new muscle fiber formation is controversial; in fact, emerging evidence indicates that their therapeutic effects occur without signs of long-term tissue engraftment and involve the paracrine secretion of cytokines and growth factors with multiple effects on the injured tissue, including modulation of inflammation and immune reaction, positive extracellular matrix (ECM) remodeling, angiogenesis and protection from apoptosis. Recently, a new role for BM-MSCs in the stimulation of muscle progenitor cells proliferation has been demonstrated, suggesting the potential ability of these cells to influence the fate of local stem cells and augment the endogenous mechanisms of repair/regeneration in the damaged tissues.

Autologous Ectopic Grafting of Cryopreserved Testicular Tissue Preserves the Fertility of Prepubescent Monkeys That Receive Sterilizing Cytotoxic Therapy

Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed. Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts. However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production. In this study, we used a prepubescent simian model to address the possibility that testicular tissue engraftment is insufficiently supported in the model to allow suitable maturation of germ cells. Briefly, we carried out autologous orthotopic grafting of cryopreserved testicular tissue from four prepubescent monkeys and one pubescent rhesus monkey after testicular irradiation and castration of the host animal. Five months after implantation of scrotal grafts, we determined that 3% to 7% of the autografts could be recovered with spermatogenesis proceeding through spermatozoa formation in 13% to 17% of the seminiferous tubules formed in the grafts. In contrast, Sertoli cell-only tubules were detected in parallel xenografts transplanted into immunocompromised mice. Our results show that cryopreservation of testicular tissue from prepubescent primates can maintain the fully functional capacity of spermatogonia to produce sperm, but that host conditions are critical for spermatogenic maturation. Furthermore, our results establish an initial perspective on the quantity of cryopreserved material needed to ensure success in preserving fertility through testicular tissue grafts.

Skin graft vascular maturation and remodeling: a multifractal approach to morphological quantification.

One important contributor to tissue graft viability is angiogenic maturation of the graft tissue bed. This study uses scale-invariant microvascular morphological quantification to track vessel maturation and remodeling in a split-thickness skin-grafting model over 21 days, comparing the results to classical techniques. Images from a previous study of split-thickness skin grafting in rats were analyzed. Microvascular morphology (fractal and multifractal dimensions, lacunarity, and vessel density) within fibrin interfaces of samples over time was quantified using classical semi-automated methods and automated multifractal and lacunarity analyses. Microvessel morphology increased in density and complexity, from three to seven days after engraftment and then regressed by 21 days. Vessel density increased from 0.07 on day 3 to 0.20 on day 7 and then decreased to 0.06 on day 21. A similar trend was seen for the fractal dimension that increased from 1.56 at three days to 1.77 at seven days then decreased to 1.57 by 21 days. Vessel diameters did not change whereas complexity and density did, signaling remodeling. This new automated analysis identified design parameters for tissue engraftment and could be used in other models of graft vessel biology to track proliferation and pruning of complex vessel beds.

External Volume Expansion Increases Subcutaneous Thickness, Cell Proliferation, and Vascular Remodeling in a Murine Model

Fat grafting is a powerful tool for soft-tissue reconstruction; however, the science behind recipient bed preparation has not been thoroughly explored. External volume expansion using suction before fat grafting has been used clinically to improve reliability and consistency of graft survival. The authors developed a murine model to investigate the underlying mechanism of external volume expansion. The authors created an external volume expansion device using a soft-silicone dome connected to a vacuum source (25 mmHg) to treat the dorsum of mice, and the response was compared with treatment with an occlusive dressing. Treated areas were monitored with magnetic resonance imaging. Remodeling of microvasculature was studied with corrosion casting on day 7. Effects on tissue thickness, number of adipocytes, cell proliferation, and blood vessel density were analyzed at 28 days. Macroscopic analysis showed tissue swelling at sites treated with the external volume expansion device by 21 days, without skin damage. On day 28, external volume expansion increased the thickness of the subcutaneous fat layer twofold, consistent with magnetic resonance imaging observations. The proliferation rate in the subcutaneous layer of expansion-treated areas increased twofold, with a net 2.2-fold increase in number of adipocytes in columns; remodeling of the vessels network occurred, with reorientation and increase of vessel diameters shown by corrosion casting and 1.9-fold augmentation of vessels density. External volume expansion applied to mouse integument induces highly proliferative and vascularized subcutaneous tissue. Recipient-site preparation using external volume expansion devices may be a promising tool to enhance cell and tissue engraftment.

Regraft from Amputated Forehead Tissue of a 4×7 cm Skin Defect Containing Bony Defects

Regraft from Amputated Forehead Tissue of a 4×7 cm Skin Defect Containing Bony Defects

In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide

Background— Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice–compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans. Methods and Results— Peripheral blood mononuclear cells 1–5×10 9 were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10 8 SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10 9 SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin. Conclusions— Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells. Clinical Trial Registration— URL: http://www.clinicaltrials.gov ; Unique identifier: NCT00972946, NCT01169935.

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

Bone-marrow-derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell-based therapy of diseased myocardium is limited by a low level of tissue engraftment. The aim of this study was the development of the bifunctional protein αCD133-glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms. We have generated and characterized a bifunctional molecule (αCD133-GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133(+) progenitor cells with high affinity. αCD133-GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133-GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133-GPVI-labeled progenitor cells reduces infarction size and preserves myocardial function. The bifunctional trapping protein αCD133-GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.