Biomat03 - Stem Cell Recruiting by Novel CXCR4 Ligands

Research outline

The stimulation of stem and progenitor cell recruitment by means of activation of the chemokine receptor CXCR4 will be investigated. New, highly active CXCR4 peptoid ligands recently developed in our laboratories will be studied. These compounds, which show an affinity for CXCR4 similar or higher compared to the natural ligand, CXCL12, are expected to strongly enhance the mobilization of adult stem cells. To achieve a controlled and continuous release, new degradable hydrogels capable of immobilizing or integrating the ligands will be developed.

We will further investigate the recruitment, attachment and fate of CXCR4-positive stem cells on polymeric matrices and artificial surfaces (e.g. titanium) of implants decorated with newly developed CXCR4 ligands immobilized on the aforementioned materials by means of suitable spacer and anchoring units. As differentiation and proliferation of stem cells is expected to occur at the site of injury (implantation), enhanced and faster healing of the damaged tissue is expected. Whereas attracted mesenchymal stem cells will differentiate into osteoblasts and hence promote bone remodeling, distinct stem cell types (e.g. hematopoietic stem cells) and progenitor cells (e.g. endothelial progenitor cells) may promote neovascularization and angiogenesis and fasten wound healing and tissue regeneration.

Publications

Schottelius, M., Osl, T., Poschenrieder, A. et al.: "[177Lu]pentixather: comprehensive preclinical evaluation of a first CXCR4-directed endoradiotherapeutic agent", 2017.

Hyafil, F., Pelisek, J., […], Poschenrieder, A. et al.: "Imaging the cytokine receptor CXCR4 in atherosclerotic plaques with the radiotracer 68Ga-pentixafor for positron emission tomography", 2017.

Poschenrieder, A., Schottelius, M., Schwaiger, M., & Wester, H.: "[64Cu]NOTA- pentixather enables high resolution PET imaging of CXCR4 expression in a preclinical lymphoma model", 2017.

Poschenrieder, A., Schottelius, M., Schwaiger, M., & Wester, H.: "Preclinical evaluation of [68Ga]NOTA-pentixafor for PET imaging of CXCR4 expression in vivo - a comparison to [68Ga]pentixafor", 2016.

Poschenrieder, A., Schottelius, M., Schwaiger, M., Kessler, H., & Wester, H.: "The influence of different metal-chelate conjugates of pentixafor on the CXCR4 affinity", 2016.

Poschenrieder, A., Osl, T., Schottelius, M. et al. : "First 18F-labeled pentixafor-based imaging agent for PET imaging of CXCR4- expression in vivo", 2016.

Kapp, T. G., Fottner, M., Maltsev, O., Kessler, H.: "Small Cause, Great Impact: Modification of the Guanidine Group in the RGD Motif Controls Integrin Subtype Selectivity", 2016.

Maltsev, O., Marelli, U., Kapp, T. G., Di Leva, F., Kessler, H.: "Stable Peptides Instead of Stapled Peptides: Highly Potent avß6-Selevtive Integrin Ligands", 2016.

Notni, J., Steiger, K., Hoffmann, F., Reich, D., Kapp, T. G., Rechenmacher, F., Wester H. J.: "Complementary, Selective PET-Imaging of Integrin Subtypes a5ß1 and avß3 Using Ga-68-Aquibeprin and Ga-68-Avebetrin”, 2016.

Mas-Moruno, C., Fraioli, R., Rechenmacher, F., Neubauer, S., Kapp, T. G., Kessler, H.: “The quest towards avß3- or a5ß1-integrin selective peptidomimetics for surface coating - History, recent advances and future perspectives”, 2016.

Stenken, J. & Poschenrieder, A.: "Bioanalytical chemistry of cytokines–A review", 2015.

Schottelius, M., Konrad, M., Osl, T., Poschenrieder, A., & Wester, H.: "An optimized strategy for the mild and efficient solution phase iodination of tyrosine residues in bioactive peptides", 2015.

Herrmann, K. & Poschenrieder, A.: "First-in-man experience of CXCR4-directed endoradiotherapy with 177Lu-and 90Y-labelled pentixather in advanced stage multiple myeloma with extensive intra-and extramedullary disease", 2015.

Rodriguez Camargo, D. C., Tripsianes, K., Kapp, T. G., et al.: "Cloning, expression and purification of the human Islet Amyloid Polypeptide (hIAPP) from Escherichia coli", 2015.

Simecek, J., Notni, J., Kapp, T. G., et al.: "Benefits of NOPO as Chelator in Gallium-68 Peptides, Examplified by Preclinical Characterization of 68Ga-NOPO-c/RGDfK)", 2014.

Rechenmacher, F., Steigerwald, K., Laufer, B., Neubauer, S., Kapp, T. G., et al.: "The Integrin Ligand c(RGDf(NMe)Nal) Reduces Neointimal Hyperplasia in a Polymer-Free Drug-Eluting Stent System", 2014.

Ray, A. M., Kapp, T. G., et al.: "Single cell tracking assay reveals an opposite effect of selective small non-peptidic integrin antagonists in U87MG glioma cells", 2014.

Kapp, T. G., et al.: "Integrin modulators: a patent review", 2013.

Simecek, J., Hermann, P., Havlickova, J., Herdtweck, E., Kapp, T. G., et al.: "A Cyclen-Based Tetraphosphinate Chelator for the Preparation of Radiolabeled Tetrameric Bioconjugates", 2013.

Team

Project team leader

PD Dr. Margret Schottelius
Pharmaceutical Radiochemistry

Alumnus

Dr. rer. nat. Tobias Kapp
Organic Chemistry and Biochemistry II

Alumna

Dr. rer. nat. Theresa Osl
Pharmaceutical Radiochemistry

Alumnus

Dr. rer. nat. Andreas Poschenrieder
Pharmaceutical Radiochemistry

Principal investigator

Professor Horst Kessler
Organic Chemistry and Biochemistry II

Principal investigator

Professor Hans-Jürgen Wester
Pharmaceutical Radiochemistry