Persistent inflammation is a major contributor to the pathogenesis of many musculoskeletal diseases. Melanie’s current aim is to combine her previous expertise in therapeutic and preventive strategies for reducing inflammation in hypoxic tissues (i.e. inhibiting the destructive effects of the complement system; promoting adenosine-mediated anti-inflammatory effects), with her more recent expertise in tissue engineering and regenerative techniques.

During Melanie’s research activities from 1998 to 2011, she investigated mechanistic aspects of the complement system in HIV infection, as well as in ischemia-reperfusion injury. She demonstrated how the complement system acts protectively against HIV viral infections, but causes substantial tissue damage in tissue that has undergone ischemia and reperfusion. Melanie also worked extensively in this period on the mechanism of adenosine-mediated anti-inflammatory effects in ischemia-reperfused organs, as well as the effects of potentially clinically therapeutic substances to treat organ damage (e.g. ischemia-reperfusion damage or excessive aggregation/thrombosis).

In recent years Melanie’s focus has changed to how tissue can be regenerated (e.g. supporting and inducing differentiation of human stem and progenitor cells for tissue-specific therapeutic developments). Her group currently aims to protect and enhance regeneration of cells during tissue repair, while simultaneously preventing unwanted inflammation in degenerative and traumatic tissues of the musculoskeletal system such as in osteoarthritis or in fracture settings.

Publications

Khella CM, Asgarian R, Horvath JM, Rolauffs B, Hart ML. An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications. Int J Mol Sci. 2021 Feb 17;22(4)

Park E, Hart ML, Rolauffs B, Stegemann JP, Annamalai RT. Bioresponsive microspheres for on‐demand delivery of anti‐inflammatory cytokines for articular cartilage repair. J Biomed Mater Res A. 2020. PMID: 31788947

Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology. Felka T, Rothdiener M, Bast S, Uynuk-Ool T, Zouhair S, Ochs BG, De Zwart P, Stoeckle U, Aicher WK, Hart ML, Shiozawa T, Grodzinsky AJ, Schenke-Layland K, Venkatesan JK, Cucchiarini M, Madry H, Kurz B, Rolauffs B. Osteoarthritis Cartilage. 2016 Jul;24(7):1200-9

Human placenta-derived CD146-positive mesenchymal stromal cells display a distinct osteogenic differentiation potential. Ulrich C, Abruzzese T, Maerz JK, Ruh M, Amend B,Benz K, Rolauffs B, Harald A, Hart ML, Aicher WK. Stem Cells and Development. 2015. 24(13): 1558-1569

Nitric oxide activates signalling by c-Raf, MEK, p-JNK and p53 in human mesenchymal stromal cells inhibits their osteogenic differentiat

Regeneration of cartilage and bone by defined subsets of mesenchymal stromal cells–potential and pitfalls. Aicher WK, Bühring HJ, Hart M, Rolauffs B, Badke A, Klein G. Advanced Drug Delivery Review. 2011. 63:342-351

ion by blocking expression of Runx2. Felka T, Ulrich C, Rolauffs B, Mittag F, Kluba T, Hart ML, Aicher WK. Journal of Stem Cell Research and Therapy. June 2014.  4: 195. doi: 10.4172/2157-7633.1000195

The TGF-β1-induced expression of matrix metalloproteinases in mesenchymal stromal cells is influenced by type of substrate. Warstat K, Felka T, Mittag F, Kluba T, Rolauffs B, Klein G, Hart ML, Aicher WK. Journal of Tissue Science & Engineering. 2011; 22:108

Cutting Edge: A2B Adenosine receptor signaling provides potent protection during intestinal ischemia/reperfusion injury.Hart ML, Jacobi B, Schittenhelm J, Henn M, Eltzschig HK. Journal of Immunolology 2009. 182:3965-3968

Extracellular adenosine production by ecto-5′-nucleotidase protects during murine hepatic ischemic preconditioning. Hart ML, Much C, Gorzolla IC, Schittenhelm J, Kloor D, Stahl GL, Eltzschig HK. Gastroenterology. 2008. 135:1739-1750

Direct treatment of mouse or human blood with soluble 5′-nucleotidase inhibits platelet aggregation. Hart ML, Köhler D, Eckle T, Kloor D, Stahl GL, Eltzschig HK. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008. 28:1477-1483

Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury. Hart ML, Henn M, Köhler D, Kloor D, Mittelbronn M, Gorzolla IC, Stahl GL, Eltzschig HK. FASEB Journal. 2008. 22:2784-2797

CD39/ectonucleoside triphosphate diphosphohydrolase 1 provides myocardial protection during cardiac ischemia/reperfusion injury. Köhler D, Eckle T, Faigle M, Grenz A, Mittelbronn M, Laucher S, Hart ML, Robson SC, Müller CE, Eltzschig HK. Circulation. 2007. 116:1784-1794

Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo. McMullen ME, Hart ML, Walsh MC, Buras J, Takahashi K, Stahl GL. Immunobiology. 2006. 211:759-766

Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. Hart ML, Ceonzo KA, Shaffer LA, Takahashi K, Rother RP, Reenstra WR, Buras JA, Stahl GL. Journal of Immunology. 2005. 174:6373-6780

Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.Pachori AS, Melo LG, Hart ML, Noiseux N, Zhang L, Morello F, Solomon SD, Stahl GL, Pratt RE, Dzau VJ. Proceedings of the National Academy of Sciences (PNAS). 2004. 101:12282-12287

Reduction of myocardial reperfusion injury by aprotinin after regional ischemia and cardioplegic arrest. Khan TA, Bianchi C, Voisine P, Feng J, Baker J, Hart M, Takahashi M, Stahl G, Sellke FW. The Journal of Thoracic and Cardiovascular Surgery. 2004. 128:602-608

Osteopetrosis, femoral fracture, and chronic osteomyelitis caused by Staphylococcus aureus small colony variants (SCV) treated by girdlestone resection–6-year follow-up.Rolauffs B, Bernhardt TM, von Eiff C, Hart ML, Bettin D. Archives of Orthopaedic and Trauma Surgery. 2002. 122:547-550

Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. Hart ML, Saifuddin M, Spear GT. Journal of General Virology. 2003. 84:353-360

High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. Hart ML, Saifuddin M, Uemura K, Bremer EG, Hooker B, Kawasaki T, Spear GT. AIDS Research and Human Retroviruses. 2002. 18:1311-1317

Cellular factors influence the binding of HIV type 1 to cells. Olinger GG, Saifuddin M, Hart ML, Spear GTAIDS Research and Human Retroviruses. 2002. 18:259-267

Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1. Saifuddin M, Hart ML, Gewurz H, Zhang Y, Spear GT. Journal of General Virology. 2000. 81:949-955