The Role of Macrophage Migration Inhibitory Factor (MIF) Family Proteins in Wound Repair and Obesity

• Applicants: Professor Dr. Jürgen Bernhagen; Privatdozent Dr. Bong-Sung Kim
• Subject Area: General and Visceral Surgery
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 394654802

• Final Report Year: 2024

Final Report Abstract

Cutaneous wound healing is a complex physiological process, in which a damage to the skin is restored. While healing of minor wounds in healthy individuals is of little concern in most cases, complex wounds with exposure of important structures or wounds in patients with underlying diseases can be threatening. In recent years, a drastic increase of obesity, which also is a known risk factor for type 2 diabetes mellitus, was observed troubling healthcare professionals globally. Wound healing, obesity and diabetes are closely intertwined but the underlying factors and mechanisms are not yet fully understood. It is believed that adipose tissue underlies a state of chronic inflammation in obese subjects, which in turn alters glucose metabolism and wound healing. A group of proteins that may play an important role in this context is the macrophage migration inhibitory factor, in short MIF, family. Its first discovered member, MIF or MIF-1, is a long-known pro-inflammatory protein whereas its recently discovered sister protein MIF-2 appears to have a more ambivalent role in inflammation. Previous preliminary results indicated that MIF-2 in particular may counteract adipose tissue inflammation and improve cutaneous wound healing, while MIF-1 acts in an opposing way. In the present project, a closer look on both proteins in cutaneous wound healing, obesity and adipose tissue inflammation was taken and ways for clinical translation were explored. The research was done in a collaboration between basic scientists and clinicians to provide a most comprehensive view on this complex but clinically relevant topic.

Publications

• Adipose-Derived Stem Cells in Bone Tissue Engineering: Useful Tools with New Applications. Stem Cells International, 2019, 1-18.
  Storti, Gabriele; Scioli, Maria Giovanna; Kim, Bong-Sung; Orlandi, Augusto & Cervelli, Valerio
  
• Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF‐2 in adipose tissue during endotoxemia. The FASEB Journal, 34(3), 4219-4233.
  Kim, Bong‐Sung; Tilstam, Pathricia V.; Arnke, Kevin; Leng, Lin; Ruhl, Tim; Piecychna, Marta; Schulte, Wibke; Sauler, Maor; Frueh, Florian S.; Storti, Gabriele; Lindenblatt, Nicole; Giovanoli, Pietro; Pallua, Norbert; Bernhagen, Jürgen & Bucala, Richard
  
• Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology. Scientific Reports, 10(1).
  Felmerer, Gunther; Stylianaki, Aikaterini; Hollmén, Maija; Ströbel, Philipp; Stepniewski, Adam; Wang, Anna; Frueh, Florian S.; Kim, Bong-Sung; Giovanoli, Pietro; Lindenblatt, Nicole & Gousopoulos, Epameinondas
  
• Microfat and Lipoconcentrate for the Treatment of Facial Scars. Clinics in Plastic Surgery, 47(1), 139-145.
  Pallua, Norbert & Kim, Bong-Sung
  
• The Effect of Hyperbaric Oxygen Therapy on Human Adipose-Derived Stem Cells. Plastic & Reconstructive Surgery, 146(2), 309-320.
  Yoshinoya, Yuriko; Böcker, Arne H.; Ruhl, Tim; Siekmann, Ullrich; Pallua, Norbert; Beier, Justus P. & Kim, Bong-Sung
  
• The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing in vivo. Journal of Plastic Surgery and Hand Surgery, 54(3), 137-144.
  Kim, Bong-Sung; Breuer, Benjamin; Arnke, Kevin; Ruhl, Tim; Hofer, Tanja; Simons, David; Knobe, Matthias; Ganse, Bergita; Guidi, Marco; Beier, Justus P.; Fuchs, Paul C.; Pallua, Norbert; Bernhagen, Jürgen & Grieb, Gerrit
  
• Macrophage Migration Inhibitory Factor—An Innovative Indicator for Free Flap Ischemia after Microsurgical Reconstruction. Healthcare, 9(6), 616.
  Megas, Ioannis-Fivos; Simons, David; Kim, Bong-Sung; Stoppe, Christian; Piatkowski, Andrzej; Fikatas, Panagiotis; Fuchs, Paul Christian; Bastiaanse, Jacqueline; Pallua, Norbert; Bernhagen, Jürgen & Grieb, Gerrit
  
• Mesenchymal Stem Cells in Adipose Tissue and Extracellular Vesicles in Ovarian Cancer Patients: A Bridge toward Metastatic Diffusion or a New Therapeutic Opportunity?. Cells, 10(8), 2117.
  Storti, Gabriele; Scioli, Maria Giovanna; Kim, Bong-Sung; Terriaca, Sonia; Fiorelli, Elena; Orlandi, Augusto & Cervelli, Valerio
  
• The Role of Macrophage Migration Inhibitory Factor in Adipose-Derived Stem Cells Under Hypoxia. Frontiers in Physiology, 12.
  Hofmann, Elena; Soppert, Josefin; Ruhl, Tim; Gousopoulos, Epameinondas; Gerra, Simona; Storti, Gabriele; Tian, Yuan; Brandhofer, Markus; Schweizer, Riccardo; Song, Seung-Yong; Lindenblatt, Nicole; Pallua, Norbert; Bernhagen, Jürgen & Kim, Bong-Sung
  
• The Stem Cell Bubble: Time to Reconsider the Mesenchymal Stem Cell Terminology. Plastic & Reconstructive Surgery, 148(3), 523e-524e.
  Kim, Bong-Sung
  
• In Vivo Evaluation of Mechanically Processed Stromal Vascular Fraction in a Chamber Vascularized by an Arteriovenous Shunt. Pharmaceutics, 14(2), 417.
  Kim, Bong-Sung; Chen, Shih-Heng; Vasella, Mauro; Guidi, Marco; Gousopoulos, Epameinondas; Lindenblatt, Nicole & Kao, Huang-Kai
  
• Oral administration of megestrol acetate can increase fat graft survival in a rat model. Journal of Plastic, Reconstructive & Aesthetic Surgery, 75(6), 1878-1885.
  Kim, Si Youn; Kook, Kwang Sik; Lee, Yong Seok; Kim, Bong Sung & Song, Seung Yong
  
• Arterial Embolism After Facial Fat Grafting: A Systematic Literature Review. Aesthetic Plastic Surgery, 47(6), 2771-2787.
  Moellhoff, Nicholas; Kuhlmann, Constanze; Frank, Konstantin; Kim, Bong-Sung; Conte, Francesco; Cotofana, Sebastian; Piccolo, Nelson S. & Pallua, Norbert
  
• Discussion: Adipose-Derived Stem Cell Extracellular Vesicles Improve Wound Closure and Angiogenesis in Diabetic Mice. Plastic & Reconstructive Surgery, 151(2), 343-344.
  Kim, Bong-Sung; Hwang, Soo-Seok & Kao, Huang-Kai
  
• Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice. International Journal of Molecular Sciences, 24(24), 17299.
  Arnke, Kevin; Pfister, Pablo; Reid, Gregory; Vasella, Mauro; Ruhl, Tim; Seitz, Ann-Kathrin; Lindenblatt, Nicole; Cinelli, Paolo & Kim, Bong-Sung
  
• Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema. Metabolites, 13(10), 1105.
  Vasella, Mauro; Wolf, Stefan; Francis, Eamon C.; Grieb, Gerrit; Pfister, Pablo; Reid, Gregory; Bernhagen, Jürgen; Lindenblatt, Nicole; Gousopoulos, Epameinondas & Kim, Bong-Sung
  
• Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair. International Journal of Molecular Sciences, 24(18), 13944.
  Vasella, Mauro; Arnke, Kevin; Dranseikiene, Dalia; Guzzi, Elia; Melega, Francesca; Reid, Gregory; Klein, Holger Jan; Schweizer, Riccardo; Tibbitt, Mark W. & Kim, Bong-Sung
  
• Outcome of Facial Burn Injuries Treated by a Nanofibrous Temporary Epidermal Layer. Journal of Clinical Medicine, 12(16), 5273.
  Vasella, Mauro; Cirebea, Jan; Gousopoulos, Epameinondas; Wang, Anna; Schweizer, Riccardo; Waldner, Matthias; Grieb, Gerrit; Buehler, Philipp; Plock, Jan Alexander & Kim, Bong-Sung
  
• The Combination of Mechanically Isolated Stromal Vascular Fraction and Fibrin Hydrogel: A Processing Protocol. Journal of Visualized Experiments(201).
  Pfister, Pablo; Reid, Gregory; Breckwoldt, Tabea; Vasella, Mauro; Seitz, Ann-Kathrin; Song, Seung Yong & Kim, Bong-Sung