Kliniken & Institute … Kliniken Zentrum für Orthopädie,… Forschungszentrum für… Publications

Selected publications

Stem Cell Biology

Kreuser, U., Buchert, J., Haase, A., Richter, W., Diederichs, S. (2020).  Initial WNT/β-Catenin Activation Enhanced Mesoderm Commitment, Extracellular Matrix Expression, Cell Aggregation and Cartilage Tissue Yield From Induced Pluripotent Stem Cells. Front. Cell Dev. Biol. 8:581331. doi: 10.3389/fcell.2020.581331.

Dreher, S. I., Fischer, J., Walker, T., Diederichs, S. and Richter, W. (2020). Significance of MEF2C and RUNX3 Regulation for Endochondral Differentiation of Human Mesenchymal Progenitor Cells. Front Cell Dev Biol. 2020 8;81. doi: 10.3389/fcell.2020.00081.

Diederichs, S., Klampfleuthner, F.A.M., Moradi, B., Richter, W. (2019). Chondral Differentiation of Induced Pluripotent Stem Cells Without Progression Into the Endochondral Pathway. Front Cell Dev Biol. 2019 Nov 1;7:270. doi: 10.3389/fcell.2019.00270.

Diederichs, S., Tonnier, V., März, M., Dreher, S.I., Geisbüsch, A., Richter, W. (2019). Regulation of WNT5A and WNT11 during MSC in vitro chondrogenesis: WNT inhibition lowers BMP and hedgehog activity, and reduces hypertrophy. Cell Mol Life Sci. 2019 Oct;76(19):3875-3889. doi: 10.1007/s00018-019-03099-0.

Buchert, J., Diederichs, S., Kreuser, U., Merle, C., Richter, W. (2019). The Role of Extracellular Matrix Expression, ERK1/2 Signaling and Cell Cohesiveness for Cartilage Yield from iPSCs. Int J Mol Sci. 2019 Sep 2;20(17). pii: E4295. doi: 10.3390/ijms20174295

Fischer, J., Knoch, N., Sims, T., Rosshirt, N., Richter, W. (2018). Time‐dependent contribution of BMP, FGF, IGF, and HH signaling to the proliferation of mesenchymal stroma cells during chondrogenesis. Cell Physiol. 2018; 233: 8962–8970.

Dexheimer, V., Gabler, J., Bomans, K., Sims, T., Omlor, G., Richter, W. (2016). Differential expression of TGF-β superfamily members and role of Smad1/5/9-signalling in chondral versus endochondral chondrocyte differentiation
Sci. Rep. 6, 36655; doi: 10.1038/srep36655.

Diederichs, S., Gabler, J., Autenrieth, J., Kynast, K. L., Merle, C., Walles, H., Utikal, J. and Richter, W. (2016). Differential regulation of SOX9 protein during chondrogenesis of induced pluripotent stem cells versus mesenchymal stromal cells: a shortcoming for cartilage formation. Stem Cells Dev. 2016 Apr 15;25(8):598-609. doi: 10.1089/scd.2015.0312.

Gabler, J., Ruetze, M., Kynast, K. L., Grossner, T., Diederichs, S. and Richter, W. (2015). Stage-Specific miRs in Chondrocyte Maturation: Differentiation-Dependent and Hypertrophy-Related miR Clusters and the miR-181 Family. Tissue Eng Part A 21, 2840-51

Diederichs, S., Zachert, K., Raiss, P. and Richter, W. (2014). Regulating chondrogenesis of human mesenchymal stromal cells with a retinoic Acid receptor-Beta inhibitor: differential sensitivity of chondral versus osteochondral development. Cell Physiol Biochem 33, 1607-19.

Fischer, J., Aulmann, A., Dexheimer, V., Grossner, T. and Richter, W. (2014). Intermittent PTHrP(1-34) exposure augments chondrogenesis and reduces hypertrophy of mesenchymal stromal cells. Stem Cells Dev 23, 2513-23.

Boeuf, S., Graf, F., Fischer, J., Moradi, B., Little, C. B. and Richter, W. (2012). Regulation of aggrecanases from the ADAMTS family and aggrecan neoepitope formation during in vitro chondrogenesis of human mesenchymal stem cells. Eur Cell Mater 23, 320-32.

Dexheimer, V., Frank, S. and Richter, W. (2012). Proliferation as a requirement for in vitro chondrogenesis of human mesenchymal stem cells. Stem Cells Dev 21, 2160-9.

Dexheimer, V., Mueller, S., Braatz, F. and Richter, W. (2011). Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age. PLoS One 6, e22980.

Boeuf, S. and Richter, W. (2010). Chondrogenesis of mesenchymal stem cells: role of tissue source and inducing factors. Stem Cell Res Ther 1, 31.

Fischer, J., Dickhut, A., Rickert, M. and Richter, W. (2010). Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis. Arthritis Rheum 62, 2696-706.

Weiss, S., Hennig, T., Bock, R., Steck, E. and Richter, W. (2010). Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J Cell Physiol 223, 84-93.

Boeuf, S., Borger, M., Hennig, T., Winter, A., Kasten, P. and Richter, W. (2009). Enhanced ITM2A expression inhibits chondrogenic differentiation of mesenchymal stem cells. Differentiation 78, 108-15.

Dickhut, A., Pelttari, K., Janicki, P., Wagner, W., Eckstein, V., Egermann, M. and Richter, W. (2009). Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in a desired differentiation stage. J Cell Physiol 219, 219-26.

Pelttari, K., Steck, E. and Richter, W. (2008). The use of mesenchymal stem cells for chondrogenesis. Injury 39 Suppl 1, S58-65.

Hennig, T., Lorenz, H., Thiel, A., Goetzke, K., Dickhut, A., Geiger, F. and Richter, W. (2007). Reduced chondrogenic potential of adipose tissue derived stromal cells correlates with an altered TGFbeta receptor and BMP profile and is overcome by BMP-6. J Cell Physiol 211, 682-91.

Pelttari, K., Winter, A., Steck, E., Goetzke, K., Hennig, T., Ochs, B. G., Aigner, T. and Richter, W. (2006). Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54, 3254-66.

Winter, A., Breit, S., Parsch, D., Benz, K., Steck, E., Hauner, H., Weber, R. M., Ewerbeck, V. and Richter, W. (2003). Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum 48, 418-29.

Brocher, J., Janicki, P., Voltz, P., Seebach, E., Neumann, E., Mueller-Ladner, U. and Richter, W. (2013). Inferior ectopic bone formation of mesenchymal stromal cells from adipose tissue compared to bone marrow: rescue by chondrogenic pre-induction. Stem Cell Res 11, 1393-406.

Janicki, P., Boeuf, S., Steck, E., Egermann, M., Kasten, P. and Richter, W. (2011). Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells. Eur Cell Mater 21, 488-507.

Janicki, P., Kasten, P., Kleinschmidt, K., Luginbuehl, R. and Richter, W. (2010). Chondrogenic pre-induction of human mesenchymal stem cells on beta-TCP: enhanced bone quality by endochondral heterotopic bone formation. Acta Biomater 6, 3292-301.

Kasten, P., Beyen, I., Niemeyer, P., Luginbuhl, R., Bohner, M. and Richter, W. (2008). Porosity and pore size of beta-tricalcium phosphate scaffold can influence protein production and osteogenic differentiation of human mesenchymal stem cells: An in vitro and in vivo study. Acta Biomater 4, 1904-1915.

Kasten, P., Vogel, J., Luginbuhl, R., Niemeyer, P., Weiss, S., Schneider, S., Kramer, M., Leo, A. and Richter, W. (2006). Influence of platelet-rich plasma on osteogenic differentiation of mesenchymal stem cells and ectopic bone formation in calcium phosphate ceramics. Cells Tissues Organs 183, 68-79.

Vogel, J. P., Szalay, K., Geiger, F., Kramer, M., Richter, W. and Kasten, P. (2006). Platelet-rich plasma improves expansion of human mesenchymal stem cells and retains differentiation capacity and in vivo bone formation in calcium phosphate ceramics. Platelets 17, 462-9.

Kasten, P., Vogel, J., Luginbuhl, R., Niemeyer, P., Tonak, M., Lorenz, H., Helbig, L., Weiss, S., Fellenberg, J., Leo, A. et al. (2005). Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier. Biomaterials 26, 5879-89.

Steck, E., Bertram, H., Abel, R., Chen, B., Winter, A. and Richter, W. (2005). Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 23, 403-11.

Melnik, S., Werth, N., Boeuf, S., Hahn, E.M., Gotterbarm, T., Anton, M., Richter, W. (2019). Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells. Stem Cell Res Ther. 2019 Mar 5;10(1):73. doi: 10.1186/s13287-019-1187-z.

Ruetze, M. and Richter, W. (2014). Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity. Expert Rev Mol Med 16, e9.

Boeuf, S., Steck, E., Pelttari, K., Hennig, T., Buneb, A., Benz, K., Witte, D., Sultmann, H., Poustka, A. and Richter, W. (2008). Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers. Osteoarthritis Cartilage 16, 48-60.

Richter, W. (2007). Cell-based cartilage repair: illusion or solution for osteoarthritis. Curr Opin Rheumatol 19, 451-6.

Tissue Engineering

Gerstner, M., Severmann, A.-C., Chasan, S., Vortkamp, A., & Richter, W. (2021). Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading. Int. J. Mol. Sci., 22(7), 3726. https://doi.org/10.3390/ijms22073726

Hecht, N., Johnstone, B., Angele, P., Walker, T., Richter, W. (2019). Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage. Osteoarthritis Cartilage. 2019 Aug;27(8):1208-1218. doi: 10.1016/j.joca.2019.04.010.

Kunisch, E., Knauf, A.K., Hesse, E., Freudenberg, U., Werner, C., Bothe, F., Diederichs, S., Richter, W. (2018). StarPEG/heparin-hydrogel based in vivo engineering of stable bizonal cartilage with a calcified bottom layer. Biofabrication. 2018 Oct 30;11(1):015001. doi: 10.1088/1758-5090/aae75a.

Praxenthaler, H., Krämer, E., Weisser, M., Hecht, N., Fischer, J., Grossner, T., Richter, W. (2018) Extracellular matrix content and WNT/β-catenin levels of cartilage determine the chondrocyte response to compressive load. Biochim Biophys Acta. 1864, 851-859
https://www.sciencedirect.com/science/article/pii/S0925443917304787

Hesse, E., Freudenberg, U., Niemietz, T., Greth, C., Weisser, M., Hagmann, S., Binner, M., Werner, C., and Richter, W.(2017) Peptide-functionalized starPEG/heparin hydrogels direct mitogenicity, cell morphology and cartilage matrix distribution in vitro and in vivo. J Tissue Eng Regen Med, doi: 10.1002/term.2404.[Ahead of print]

Scholtes, S., Krämer, E., Weisser, M., Roth, W., Luginbühl, R., Grossner, T., Richter, W. (2018) Global chondrocyte gene expression after a single anabolic loading period: Time evolution and re-inducibility of mechano-responses. J Cell Physiol. 2018; 233: 699–711

Fischer, J., Ortel, M., Hagmann, S., Hoeflich, A., Richter, W. Role of PTHrP(1-34) Pulse Frequency Versus Pulse Duration to Enhance Mesenchymal Stromal Cell Chondrogenesis. J Cell Physiol. 2016 Dec;231(12):2673-81. doi: 10.1002/jcp.25369

Fischer, J., Aulmann, A., Dexheimer, V., Grossner, T. and Richter, W. Intermittent PTHrP(1-34) exposure augments chondrogenesis and reduces hypertrophy of mesenchymal stromal cells. Stem Cells Dev 23, 2513-23 (2014).

Krase, A., Abedian, R., Steck, E., Hurschler, C. and Richter, W. (2014). BMP activation and Wnt-signalling affect biochemistry and functional biomechanical properties of cartilage tissue engineering constructs. Osteoarthritis Cartilage 22, 284-92.  

Wagner-Ecker, M., Voltz, P., Egermann, M. and Richter, W. (2013). The collagen component of biological bone graft substitutes promotes ectopic bone formation by human mesenchymal stem cells. Acta Biomater 9, 7298-307.    

Diederichs, S., Baral, K., Tanner, M. and Richter, W. (2012). Interplay between local versus soluble transforming growth factor-beta and fibrin scaffolds: role of cells and impact on human mesenchymal stem cell chondrogenesis. Tissue Eng Part A 18, 1140-50.

Steck, E., Boeuf, S., Gabler, J., Werth, N., Schnatzer, P., Diederichs, S. and Richter, W. (2012). Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions. J Mol Med (Berl) 90, 1185-95.

Dickhut, A., Dexheimer, V., Martin, K., Lauinger, R., Heisel, C. and Richter, W. (2010). Chondrogenesis of human mesenchymal stem cells by local transforming growth factor-beta delivery in a biphasic resorbable carrier. Tissue Eng Part A 16, 453-64.

Steck, E., Bertram, H., Walther, A., Brohm, K., Mrozik, B., Rathmann, M., Merle, C., Gelinsky, M. and Richter, W. (2010). Enhanced biochemical and biomechanical properties of scaffolds generated by flock technology for cartilage tissue engineering. Tissue Eng Part A 16, 3697-707.

Dickhut, A., Gottwald, E., Steck, E., Heisel, C. and Richter, W. (2008). Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo. Front Biosci 13, 4517-28.

Pelttari, K., Lorenz, H., Boeuf, S., Templin, M. F., Bischel, O., Goetzke, K., Hsu, H. Y., Steck, E. and Richter, W. (2008). Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo. Arthritis Rheum 58, 467-74.

Fehrenbacher, A., Steck, E., Roth, W., Pahmeier, A. and Richter, W. (2006). Long-term mechanical loading of chondrocyte-chitosan biocomposites in vitro enhanced their proteoglycan and collagen content. Biorheology 43, 709-20.

Benz, K., Breit, S., Lukoschek, M., Mau, H. and Richter, W. (2002). Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes. Biochem Biophys Res Commun 293, 284-92.

Regenerative Orthopaedics

Bothe, F., Lotz, B., Seebach, E., Fischer, J., Hesse, E., Diederichs, S., Richter, W. (2018). Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen. Acta Biomater. 2018 Aug;76:135-145. doi: 10.1016/j.actbio.2018.06.026.

Seebach, E., Holschbach, J., Buchta, N., Bitsch, R. G., Kleinschmidt, K. and Richter, W. (2015). Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis. Acta Biomater.

Kleinschmidt, K., Wagner-Ecker, M., Bartek, B., Holschbach, J. and Richter, W. (2014). Superior angiogenic potential of GDF-5 and GDF-5(V453/V456) compared with BMP-2 in a rabbit long-bone defect model. J Bone Joint Surg Am 96, 1699-707.

Seebach, E., Freischmidt, H., Holschbach, J., Fellenberg, J. and Richter, W. (2014). Mesenchymal stroma cells trigger early attraction of M1 macrophages and endothelial cells into fibrin hydrogels, stimulating long bone healing without long-term engraftment. Acta Biomater 10, 4730-41.

Kleinschmidt, K., Ploeger, F., Nickel, J., Glockenmeier, J., Kunz, P. and Richter, W. (2013). Enhanced reconstruction of long bone architecture by a growth factor mutant combining positive features of GDF-5 and BMP-2. Biomaterials 34, 5926-36.

Geiger, F., Bertram, H., Berger, I., Lorenz, H., Wall, O., Eckhardt, C., Simank, H. G. and Richter, W. (2005). Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects. J Bone Miner Res 20, 2028-35.

Diederichs, S., Renz, Y., Hagmann, S., Lotz, B., Seebach, E., Richter, W. (2017). Stimulation of a calcified cartilage connecting zone by GDF-5-augmented fibrin hydrogel in a novel layered ectopic in vivo model. J Biomed Mater Res B Appl Biomater. 2018 Aug;106(6):2214-2224. doi: 10.1002/jbm.b.34027.

Niemietz, T., Zass, G., Hagmann, S., Diederichs, S., Gotterbarm, T. and Richter, W. (2014). Xenogeneic transplantation of articular chondrocytes into full-thickness articular cartilage defects in minipigs: fate of cells and the role of macrophages. Cell Tissue Res 358, 749-61.   

Gotterbarm, T., Breusch, S. J., Vilei, S. B., Mainil-Varlet, P., Richter, W. and Jung, M. (2013). No effect of subperiosteal growth factor application on periosteal neo-chondrogenesis in osteoperiosteal bone grafts for osteochondral defect repair. Int Orthop 37, 1171-8.

Zeifang, F., Oberle, D., Nierhoff, C., Richter, W., Moradi, B. and Schmitt, H. (2010). Autologous chondrocyte implantation using the original periosteum-cover technique versus matrix-associated autologous chondrocyte implantation: a randomized clinical trial. Am J Sports Med 38, 924-33.

Steck, E., Fischer, J., Lorenz, H., Gotterbarm, T., Jung, M. and Richter, W. (2009). Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage. Stem Cells Dev 18, 969-78.

Gotterbarm, T., Richter, W., Jung, M., Berardi Vilei, S., Mainil-Varlet, P., Yamashita, T. and Breusch, S. J. (2006). An in vivo study of a growth-factor enhanced, cell free, two-layered collagen-tricalcium phosphate in deep osteochondral defects. Biomaterials 27, 3387-95.

Omlor, G.W., Lorenz, S., Nerlich, A.G., Guehring, T., Richter, W. (2018). Disc cell therapy with bone‑marrow‑derived autologous mesenchymal stromal cells in a large porcine disc degeneration model. Eur Spine J. 2018 Oct;27(10):2639-2649. doi: 10.1007/s00586-018-5728-4.

Omlor, G. W., Fischer, J., Kleinschmitt, K., Benz, K., Holschbach, J., Brohm, K., Anton, M., Guehring, T. and Richter, W. (2014). Short-term follow-up of disc cell therapy in a porcine nucleotomy model with an albumin-hyaluronan hydrogel: in vivo and in vitro results of metabolic disc cell activity and implant distribution. Eur Spine J 23, 1837-47.

Omlor, G. W., Bertram, H., Kleinschmidt, K., Fischer, J., Brohm, K., Guehring, T., Anton, M. and Richter, W. (2010). Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs. Eur Spine J 19, 601-12.

Kroeber, M. W., Unglaub, F., Wang, H., Schmid, C., Thomsen, M., Nerlich, A. and Richter, W. (2002). New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine (Phila Pa 1976) 27, 2684-90.