axis 1 PI: Pierre Layrolle (DR Inserm), Philippe Rosset (PU-PH, orthopedic surgeon, CHU Tours)

Post-doc : Meadhbh Brennan (PARAGEN, Marie Curie Fellow, Harvard Medical School, USA)

PhD students: Luciano Vidal (reconstruction of large bone defects)

                      Walid Lakhal (reconstruction of articular bone/ligaments)

                      Paul Humbert (biomarkers of bone healing)

Technicians and engineers: Bénédicte Brulin (IE Inserm), Julien de Lima (AI CDD Inserm)

Manager for the european projects: Solenne Lhéritier

Unconsolidated fractures and the reconstruction of large bone defects are clinical problems requiring numerous surgeries. We have shown at the preclinical and clinical level that mesenchymal stromal stem cells associated with a biomaterial are capable of inducing bone regeneration and healing of fractures. However, we observed an important heterogeneity between the cells of different patients or according to their tissue origin (eg bone marrow, adipose tissue). It seems that mesenchymal stem cells have a predominant paracrine effect to induce differentiation of monocytes into osteoclasts and then to trigger the process of bone regeneration. Our project aims to understand the cellular communications involved in bone healing. We also want to develop an anatomic pre-vascularized bone transplant by 3D bio-printing to regenerate large bone defects.

link to the clinical trials REBORNE
link to the H2020 project ORTHOUNION or here
link to the MSCA project PARAGEN
link to the H2020 project MAXIBONE
link to the French Ligue against neurofibromatosis
PHRC MOCASO : Support for the consolidation of long bone fractures by association of autologous concentrated bone marrow and bone substitute (30 patients)



Major recent publications:

  • Gjerde C, Mustafa K, Hellem S, Rojewski M, Gjengedal H, Yassin MA, Feng X, Skaale S, Berge T, Rosen A, Shi XQ, Ahmed AB, Gjertsen BT, Schrezenmeier H, Layrolle P. Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther. 2018;9:213
  • Gómez-Barrena E, Rosset P, Gebhard F, Hernigou P, Baldini N, Rouard H, Sensebé L, Gonzalo-Daganzo RM, Giordano R, Padilla-Eguiluz N, García-Rey E, Cordero-Ampuero J, Rubio-Suárez JC, Stanovici J, Ehrnthaller C, Huber-Lang M, Flouzat-Lachaniette CH, Chevallier N, Donati DM, Ciapetti G, Fleury S, Fernandez MN, Cabrera JR, Avendaño-Solá C, Montemurro T, Panaitescu C, Veronesi E, Rojewski MT, Lotfi R, Dominici M, Schrezenmeier H, Layrolle P. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial. Biomaterials. 2018 S0142-9612 30205-9
  • Brennan MA, Renaud A, Guilloton F, Mebarki M, Trichet V, Sensebé L, Deschaseaux F, Chevallier N, Layrolle P. Inferior In Vivo Osteogenesis and Superior Angiogeneis of Human Adipose Tissue-Compared with Bone Marrow-Derived Stromal Stem Cells Cultured in Xeno-Free Conditions. Stem Cells Transl Med. 2017;6:2160-2172.
  • Stanovici J, Le Nail LR, Brennan MA, Vidal L, Trichet V, Rosset P, Layrolle P. Bone regeneration strategies with bone marrow stromal cells in orthopaedic surgery. Curr Res Transl Med. 2016;64(2):83-90.
  • Guihard P, Boutet MA, Brounais-Le Royer B, Gamblin AL, Amiaud J, Renaud A, Berreur M, Rédini F, Heymann D, Layrolle P, Blanchard F. Oncostatin M, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury. Am J Pathol, 185:765-75, 2015.
  • Gamblin AL, Brennan MA, Renaud A, Yagita H, Lézot F, Heymann D, Trichet V, Layrolle P. Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages. Biomaterials. 2014;35(36):9660-7.
  • Brennan MÁ, Renaud A, Amiaud J, Rojewski MT, Schrezenmeier H, Heymann D, Trichet V, Layrolle P. Pre-clinical studies of bone regeneration with human bone marrow stromal cells and biphasic calcium phosphate. Stem Cell Res Ther. 2014;5(5):114.
  • Gamblin AL, Renaud A, Charrier C, Hulin P, Louarn G, Heymann D, Trichet V, Layrolle P. Osteoblastic and osteoclastic differentiation of human mesenchymal stem cells and monocytes in a miniaturized three-dimensional culture with mineral granules. Acta Biomater. 2014;10(12):5139-47.
  • Rosset P, Deschaseaux F, Layrolle P. Cell therapy for bone repair. Orthop Traumatol Surg Res. 2014;100(1 Suppl):S107-12.
  • Guihard P, Danger Y, Brounais B, David E, Brion R, Delecrin J, Richards CD, Chevalier S, Rédini F, Heymann D, Gascan H, Blanchard F. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling. Stem Cells. 2012;30(4):762-72.