Bone marrow concentrate and expanded mesenchymal stromal cell surnatants as cell-free approaches for the treatment of osteochondral defects in a preclinical animal model
- 131 Downloads
To evaluate the regenerative potential of surnatants (SNs) from bone marrow concentrate (SN-BMC) and expanded mesenchymal stromal cells (SN-MSCs) loaded onto a collagen scaffold (SC) in comparison with cell-based treatments (BMC and MSCs) in an osteochondral (OC) defect model in rabbits.
OC defects (3 × 5 mm) were created in the rabbit femoral condyles and treated with SC alone or combined with SN-BMC, SN-MSCs, BMC, and MSCs. In control groups, the defects were left untreated. At three and six months, the quality of regenerated tissue was evaluated with macroscopic, histologic, microtomographic, and immunohistochemical assessments. The production of several immunoenzymatic markers was measured in the synovial fluid.
All proposed treatments improved OC regeneration in comparison with untreated and SC-treated defects. Both BMC and MSCs showed a similar healing potential than their respective SNs, with the best performance exerted by BMC as demonstrated with macroscopic and histological scores and type I and II collagen results.
SNs loaded onto SC exerted a positive effect on OC defect regeneration, underlying the biological significance of the trophic factors, thus potentially opening new opportunities for the use of cell-free-based therapies. BMC was confirmed to be the most beneficial treatment.
KeywordsOsteochondral defect In vivo model Cell-free approach Bone marrow concentrate Mesenchymal stromal cells
This work was partially supported by the Ministry of Health-Ricerca Corrente to the IRCCS Rizzoli Orthopaedic Institute and by a grant from Regione Emilia Romagna: Programma di Ricerca Regione-Università 2010–2012—Strategic Program “Regenerative Medicine of Cartilage and Bone” (PRUa1RI-2012-007).
Compliance with ethical standards
The experimental protocol and surgical procedures were approved by a local Ethical Committee and authorized by the Italian Ministry of Health (Title of the project: One-step surgery with stem cells for the treatment of osteochondral lesions—No. 0017661, approved on May 29, 2013).
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Hofer HR, Tuan RS (2016) Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther 7(131). https://doi.org/10.1186/s13287-016-0394-0
- 2.Cavallo C, Desando G, Ferrari A, Zini N, Mariani E, Grigolo B (2016) Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells. J Biol Regul Homeost Agents 30:409–420Google Scholar
- 4.Sartori M, Pagani S, Ferrari A, Costa V, Carina V, Figallo E, Maltarello MC, Martini L, Fini M, Giavaresi G (2017) A new bi-layered scaffold for osteochondral tissue regeneration: in vitro and in vivo preclinical investigations. Mater Sci Eng C Mater Biol Appl 70:101–111. https://doi.org/10.1016/j.msec.2016.08.027 CrossRefGoogle Scholar
- 6.Desando G, Giavaresi G, Cavallo C, Bartolotti I, Sartoni F, Nicoli Aldini N, Martini L, Parrilli A, Mariani E, Fini M, Grigolo B (2016) Autologous bone marrow concentrate in a sheep model of osteoarthritis: new perspectives for cartilage and meniscus repair. Tissue Eng Part C Methods 22:608–619. https://doi.org/10.1089/ten.TEC.2016.0033 CrossRefGoogle Scholar
- 7.Veronesi F, Cadossi M, Giavaresi G, Martini L, Setti S, Buda R, Giannini S, Fini M (2015) Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: an in vivo study. BMC Musculoskelet Disord 16(233). https://doi.org/10.1186/s12891-015-0683-2
- 8.Desando G, Bartolotti I, Vannini F, Cavallo C, Castagnini F, Buda R, Giannini S, Mosca M, Mariani E, Grigolo B (2017) Repair potential of matrix-induced bone marrow aspirate concentrate and matrix-induced autologous chondrocyte implantation for talar osteochondral repair: patterns of some catabolic, inflammatory, and pain mediators. Cartilage 8:50–60CrossRefGoogle Scholar
- 12.Cavallo C, Desando G, Cattini L, Cavallo M, Buda R, Giannini S, Facchini A, Grigolo B (2013) Bone marrow concentrated cell transplantation: rationale for its use in the treatment of human osteochondral lesions. J Biol Regul Homeost Agents 27:165–175Google Scholar
- 14.O’Driscoll SW, Keeley FW, Salter RB (1986) The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An experimental investigation in the bone. J Bone Joint Surg Am 68:1017–1035CrossRefGoogle Scholar
- 15.R Development Core Team (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org
- 18.Hochrein A, Zinser W, Spahn G, Angele P, Löer I, Albrecht D, Niemeyer P (2018) What parameters affect knee function in patients with untreated cartilage defects: baseline data from the German Cartilage Registry. Int Orthop. https://doi.org/10.1007/s00264-018-4125-2
- 23.Hernigou J, Vertongen P, Chahidi E, Kyriakidis T, Dehoux JP, Crutzen M, Boutry S, Larbanoix L, Houben S, Gaspard N, Koulalis D, Rasschaert J (2018) Effects of press-fit biphasic (collagen and HA/βTCP) scaffold with cell-based therapy on cartilage and subchondral bone repair knee defect in rabbits. Int Orthop 42:1755–1767. https://doi.org/10.1007/s00264-018-3999-3 CrossRefGoogle Scholar
- 24.Santo VE, Gomes ME, Mano JF, Reis RL (2013) Controlled release strategies for bone, cartilage, and osteochondral engineering--part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev 19:327–352. https://doi.org/10.1089/ten.TEB.2012.0138 CrossRefGoogle Scholar
- 26.Zhang Z, Li L, Yang W, Cao Y, Shi Y, Li X, Zhang Q (2017) The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits. Osteoarthr Cartil 25:309–320. https://doi.org/10.1016/j.joca.2016.09.010 CrossRefGoogle Scholar
- 27.Lin H, Hay E, Latourte A, Funck-Brentano T, Bouaziz W, Ea HK, Khatib AM, Richette P, Cohen-Solal M (2018) Proprotein convertase furin inhibits matrix metalloproteinase 13 in a TGFβ-dependent manner and limits osteoarthritis in mice. Sci Rep 8(10488). https://doi.org/10.1038/s41598-018-28713-2