DFG Collaborative Research Centre 1444
This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.
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Promoting humeral head fracture healing by local immunomodulation - A phase I/IIa, prospective, mono-centre, randomized, open labelled, controlled study
The process of fracture healing begins with a pro-inflammatory response that involves the activation and accumulation of immune cells at the site of injury and the production of high levels of cytokines such as TNF and IFN. The timely resolution of this acute inflammation is critical for the subsequent healing phases in which the original architecture of the damaged tissue is restored. T cells are important modulators of endogenous regeneration, and inadequate fracture healing in humans correlates significantly with elevated levels of circulating CD8+ effector memory T cells, which locally maintain an inflammatory environment and delay tissue regeneration. A local pharmacological treatment designed to modulate the balance between CD8+ effector and CD4+ regulatory T cells to promote healing is being tested in a current phase I/IIa clinical trial (IloBone). Mechanistic studies are also being performed to better understand the role of injury-related inflammatory processes in other tissues (e.g. cartilage, tendon or muscle) and to investigate the mode of action of other therapeutic approaches. This including exploratory efficacy studies on cell-based therapies or (already clinically used) immunomodulatory interventions, such as the use of platelet-rich plasma.
Ilobpone Study
A phase I/IIa, prospective, mono-center, randomized, open labeled, controlled study to assess the safety and efficacy of applying Iloprost locally in the fracture site to promote bone healing in patients with proximal humeral fracture
Sponsor Protocol Code: SIFU17
EudraCT Number: 2017-003813-24
The influence of circulating and local immune cells on tissue regeneration
Inflammatory Response | Energy Supply & Consumption
We are investigating how the systemic and local immune cell composition influences the initial inflammatory response and the process of tissue healing. Our study provides new insights into the immunology of the human bone marrow and its involvement in orthopedic conditions.
Bucher et al. Exp Mol Med. 2022 | In collaboration subproject P01 and the central service project C01
Cell-based approaches to enhance musculoskeletal regeneration
Inflammatory Response | Energy Supply & Consumption
Fundamental understanding of their regenerative function, their interaction with the injury microenvironment and their impairment by adverse conditions are essential for effective application of cell-based therapies.
Kotsaris G et al. NPJ Regen Med. 2023 | In collaboration with subproject P04
Hochmann et al. Sci Transl Med. 2023 | In collaboration with subprojects P01, P02 and P05
Drzeniek NM et al. Biomaterials. 2023 | In collaboration with subproject P01
Brachtl et al. Cells. 2022 | In collaboration subprojects with P01 and P05
Drzeniek NM et al. Biofabrication. 2021 | In collaboration with subproject P01
Quality and efficacy of platelet-rich plasma (PRP) therapies
Inflammatory Response | Energy Supply & Consumption
Platelet-rich plasma (PRP) therapy is a promising approach for the treatment of musculoskeletal disorders such as tendinopathies and osteoarthritis (OA). The composition of PRP is determined by the immune cell and cytokine profile of the donor and the method of preparation, which affects its efficacy.
Niemann et al. Arthritis Research & Therapy 2023 | In collabroation with the central service project C01
Initial immune reactions during joint inflammation
Inflammatory Response | Energy Supply & Consumption
Rheumatoid arthritis is a chronic disease in which the immune system attacks and damages joint tissue. To study the interactions between immune and tissue cells at the onset of the disease, we have established an animal model of collagen antibody-induced arthritis (CAIA).
Maleitzke et al. STAR Protoc.2022 | In collaboration with subproject P15
The infrapatellar fat pad as a source of inflammation in knee osteoarthritis (OA) and its interactions with the surrounding joint tissue
Inflammatory Response | Energy Supply & Consumption
The infrapatellar fat pad (IFP) may play a role in knee OA by influencing cartilage inflammation, degradation and repair. We describe the complex relationships between the IFP and adjacent tissues. This may provide a better understanding of the causes and targeted treatments of knee OA.
Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation
Inflammatory Response | Energy Supply & Consumption
Osteochondritis dissecans (OCD) is a condition in which fragments of cartilage (loose bodies (LBs) become completely detached from the joint. However, these LBs could be used for autologous chondrocyte implantation (ACI) to repair the cartilage defects.
Textor M et al. Int J Mol Sci. 2023 | In Zusammenarbeit mit Teilprojekt P05 und dem Zentralen Service Projekt C01
Team
Ilobone Study
Shaping the inflammatory injury response: Clinical validation of Iloprost as a local immune modulation strategy to enhance bone regeneration - IloBone a phase I/IIa study
Ilobone Study | Knee Osteoarthritis (OA)
Joint Inflammmation | Knee Osteoarthritis
Ilobone Study
Immune Cells & Tissue Regeneration | Platelet Rich Plasma (PRP) Therapies
Ilobone Study
Mechanism of Regenerative Cell Action in Osteoarthritis
Publications
- Authors:Kotsaris, G.; Qazi, T. H.; Bucher, C. H., Zahid, H.; Pohle-Kronawitter, S.; Ugorets, V.; Jarassier, W.; Borno, S.; Timmermann, B.; Giesecke-Thiel, C.; Economides, A. N.; Le Grand, F.; Vallecillo-Garcia, P.; Knaus, P.; Geissler, S.; Stricker, S.
Journal:NPJ Regen Med Year:2023; Volume:8Issue:(1):Pages:19.
Title:Odd skipped-related 1 controls the pro-regenerative response of fibro-adipogenic progenitors - Authors:Hochmann, S.; Ou, K.; Poupardin, R.; Mittermeir, M.; Textor, M.; Ali, S.; Wolf, M.; Ellinghaus, A.; Jacobi, D.; Elmiger, J. A. J.; Donsante, S.; Riminucci, M.; Schafer, R.; Kornak, U.; Klein, O.; Schallmoser, K.; Schmidt-Bleek, K.; Duda, G. N.; Polansky, J. K.; Geissler, S.; Strunk, D.
Journal:Sci Transl Med Year:2023; Volume:15Issue:(688):Pages:eabm7477.
Title:The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells - Authors:Burkhardt, L. M.; Bucher, C. H.; Loffler, J.; Rinne, C.; Duda, G. N.; Geissler, S.; Schulz, T. J.; Schmidt-Bleek, K.
Journal:Front Cell Dev Biol. Year:2023; Volume:11:Pages:1104709.
Title:The benefits of adipocyte metabolism in bone health and regeneration - Authors:Textor, M.; Hoburg, A.; Lehnigk, R.; Perka, C.; Duda, G. N.; Reinke, S.; Blankenstein, A.; Hochmann, S.; Stockinger, A.; Resch, H.; Wolf, M.; Strunk, D.; Geissler, S.
Journal:Int J Mol Sci Year:2023; Volume:24Issue:(2)
Title:Chondrocyte Isolation from Loose Bodies-An Option for Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation - Authors:Drzeniek, N. M.; Kahwaji, N.; Schlickeiser, S.; Reinke, P.; Geissler, S.; Volk, H. D.; Gossen, M.
Journal:Biomaterials Year:2023; Volume:294:Pages:121971.
Title:Immuno-engineered mRNA combined with cell adhesive niche for synergistic modulation of the MSC secretome - Authors:Niemann, M.; Ort, M.; Lauterbach, L.; Streitz, M.; Wilhelm, A.; Grutz, G.; Fleckenstein, F. N.; Graef, F.; Blankenstein, A.; Reinke, S.; Stockle, U.; Perka, C.; Duda, G. N.; Geissler, S.; Winkler, T.; Maleitzke, T.
Journal:Arthritis Res Ther Year:2023; Volume:25Issue:(1):Pages:6.
Title:Individual immune cell and cytokine profiles determine platelet-rich plasma composition - Authors:Duda, G. N.; Geissler, S.; Checa, S.; Tsitsilonis, S.; Petersen, A.; Schmidt-Bleek, K.
Journal:Nat Rev Rheumatol Year:2023; Volume:19Issue:(2):Pages:78-95.
Title:The decisive early phase of bone regeneration - Authors:Bucher, C. H.; Berkmann, J. C.; Burkhardt, L. M.; Paschke, C.; Schlundt, C.; Lang, A.; Wolter, A.; Damerau, A.; Geissler, S.; Volk, H. D.; Duda, G. N.; Schmidt-Bleek, K.
Journal:Exp Mol Med Year:2022; Volume:54Issue:(8):Pages:1262-1276.
Title:Local immune cell contributions to fracture healing in aged individuals - A novel role for interleukin 22 - Authors:Zhou, S.; Maleitzke, T.; Geissler, S.; Hildebrandt, A.; Fleckenstein, F. N.; Niemann, M.; Fischer, H.; Perka, C.; Duda, G. N.; Winkler, T.
Journal:J Orthop Res Year:2022; Volume:40Issue:(7):Pages:1492-1504.
Title:Source and hub of inflammation: The infrapatellar fat pad and its interactions with articular tissues during knee osteoarthritis - Authors:Brachtl, G.; Poupardin, R.; Hochmann, S.; Raninger, A.; Jurchott, K.; Streitz, M.; Schlickeiser, S.; Oeller, M.; Wolf, M.; Schallmoser, K.; Volk, H. D.; Geissler, S.; Strunk, D.
Journal:Cells Year:2022; Volume:11Issue:(6)
Title:Batch Effects during Human Bone Marrow Stromal Cell Propagation Prevail Donor Variation and Culture Duration: Impact on Genotype, Phenotype and Function - Authors:Drzeniek, N. M.; Mazzocchi, A.; Schlickeiser, S.; Forsythe, S. D.; Moll, G.; Geissler, S.; Reinke, P.; Gossen, M.; Gorantla, V. S.; Volk, H. D.; Soker, S.
Journal:Biofabrication Year:2021; Volume:13Issue:(4)
Title:Bio-instructive hydrogel expands the paracrine potency of mesenchymal stem cells
