Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications
Abstract
:1. Introduction
2. Molecular Characteristics of Adipose-Derived Stromal/Stem Cells (ASCs): Gene Expression Profile and Secretome Analysis
3. Molecular Mechanisms Responsible for Osteogenic Commitment of ASCs
4. Clinical Case Reports: ASCs Combined with Bioscaffolds for Craniomaxillofacial Bone Regeneration
5. Clinical Trials: Adipose-Derived Mesenchymal Stem Cells for the Treatment of Craniomaxillofacial Bone Defects
6. Conclusions and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Bauer, T.W.; Muschler, G.F. Bone graft materials: An overview of the basic science. Clin. Orthop. Relat. Res. 2000, 371, 10–27. [Google Scholar] [CrossRef]
- De Long, W.G.; Einhorn, T.A.; Koval, K.; McKee, M.; Smith, W.; Sanders, R.; Watson, T. Bone grafts and bone graft substitutes in orthopaedic trauma surgery: A critical analysis. J. Bone Jt. Surg. Am. 2007, 89, 649–658. [Google Scholar] [CrossRef]
- Polo-Corrales, L.; Latorre-Esteves, M.; Ramirez-Vick, J.E. Scaffold design for bone regeneration. J. Nanosci. Nanotechnol. 2014, 14, 15–56. [Google Scholar] [CrossRef] [PubMed]
- Smith, E.; Kanczler, J.; Gothard, D.; Roberts, C.; Wells, J.; White, L.; Qutachi, O.; Sawkins, M.; Peto, H.; Rashidi, H. Evaluation of skeletal tissue repair, part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model. Acta Biomater. 2014, 10, 4186–4196. [Google Scholar] [CrossRef] [PubMed]
- Barba, M.; Cicione, C.; Bernardini, C.; Michetti, F.; Lattanzi, W. Adipose-derived mesenchymal cells for bone regereneration: State of the art. BioMed Res. Int. 2013, 2013, 416391. [Google Scholar] [CrossRef] [PubMed]
- Morcos, M.W.; Al-Jallad, H.; Hamdy, R. Comprehensive review of adipose stem cells and their implication in distraction osteogenesis and bone regeneration. BioMed Res. Int. 2015, 2015, 842975. [Google Scholar] [CrossRef] [PubMed]
- Thesleff, T.; Lehtimaki, K.; Niskakangas, T.; Mannerstrom, B.; Miettinen, S.; Suuronen, R.; Ohman, J. Cranioplasty with adipose-derived stem cells and biomaterial: A novel method for cranial reconstruction. Neurosurgery 2011, 68, 1535–1540. [Google Scholar] [CrossRef] [PubMed]
- De Francesco, F.; Ricci, G.; D’Andrea, F.; Nicoletti, G.F.; Ferraro, G.A. Human adipose stem cells: From bench to bedside. Tissue Eng. Part B Rev. 2015, 21, 572–584. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marędziak, M.; Marycz, K.; Lewandowski, D.; Siudzińska, A.; Śmieszek, A. Static magnetic field enhances synthesis and secretion of membrane-derived microvesicles (MVs) rich in VEGF and BMP-2 in equine adipose-derived stromal cells (EqASCs)—A new approach in veterinary regenerative medicine. In Vitro Cell. Dev. Biol. Anim. 2015, 51, 230–240. [Google Scholar] [CrossRef] [PubMed]
- Kang, T.; Jones, T.M.; Naddell, C.; Bacanamwo, M.; Calvert, J.W.; Thompson, W.E.; Bond, V.C.; Chen, Y.E.; Liu, D. Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA-31. Stem Cells Transl. Med. 2016, 5, 440–450. [Google Scholar] [CrossRef] [PubMed]
- Alvira-Gonzalez, J.; Sanchez-Garces, M.A.; Cairo, J.R.; Del Pozo, M.R.; Sanchez, C.M.; Gay-Escoda, C. Assessment of bone regeneration using adipose-derived stem cells in critical-size alveolar ridge defects: An experimental study in a dog model. Int. J. Oral Maxillofac. Implants 2016, 31, 196–203. [Google Scholar] [CrossRef] [PubMed]
- Sacak, B.; Certel, F.; Akdeniz, Z.D.; Karademir, B.; Ercan, F.; Ozkan, N.; Akpinar, I.N.; Celebiler, O. Repair of critical size defects using bioactive glass seeded with adipose-derived mesenchymal stem cells. J. Biomed. Mater. Res. B Appl. Biomater. 2017, 105, 1002–1008. [Google Scholar] [CrossRef] [PubMed]
- Tajima, S.; Tobita, M.; Orbay, H.; Hyakusoku, H.; Mizuno, H. Direct and indirect effects of a combination of adipose-derived stem cells and platelet-rich plasma on bone regeneration. Tissue Eng. Part A 2015, 21, 895–905. [Google Scholar] [CrossRef] [PubMed]
- Lendeckel, S.; Jodicke, A.; Christophis, P.; Heidinger, K.; Wolff, J.; Fraser, J.K.; Hedrick, M.H.; Berthold, L.; Howaldt, H.P. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: Case report. J. Craniomaxillofac. Surg. 2004, 32, 370–373. [Google Scholar] [CrossRef] [PubMed]
- Mesimaki, K.; Lindroos, B.; Tornwall, J.; Mauno, J.; Lindqvist, C.; Kontio, R.; Miettinen, S.; Suuronen, R. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int. J. Oral Maxillofac. Surg. 2009, 38, 201–209. [Google Scholar] [CrossRef] [PubMed]
- Sandor, G.K. Tissue engineering of bone: Clinical observations with adipose-derived stem cells, resorbable scaffolds, and growth factors. Ann. Maxillofac. Surg. 2012, 2, 8–11. [Google Scholar] [CrossRef] [PubMed]
- Sandor, G.K.; Numminen, J.; Wolff, J.; Thesleff, T.; Miettinen, A.; Tuovinen, V.J.; Mannerstrom, B.; Patrikoski, M.; Seppanen, R.; Miettinen, S.; et al. Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects. Stem Cells Transl. Med. 2014, 3, 530–540. [Google Scholar] [CrossRef] [PubMed]
- Wolff, J.; Sandor, G.K.; Miettinen, A.; Tuovinen, V.J.; Mannerstrom, B.; Patrikoski, M.; Miettinen, S. GMP-level adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: Experience with three cases. Ann. Maxillofac. Surg. 2013, 3, 114–125. [Google Scholar] [PubMed]
- Sandor, G.K.; Tuovinen, V.J.; Wolff, J.; Patrikoski, M.; Jokinen, J.; Nieminen, E.; Mannerstrom, B.; Lappalainen, O.P.; Seppanen, R.; Miettinen, S. Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect: A case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration. J. Oral Maxillofac. Surg. 2013, 71, 938–950. [Google Scholar] [CrossRef] [PubMed]
- Marędziak, M.; Marycz, K.; Tomaszewski, K.A.; Kornicka, K.; Henry, B.M. The influence of aging on the regenerative potential of human adipose derived mesenchymal stem cells. Stem Cells Int. 2016, 2016, 2152435. [Google Scholar] [CrossRef] [PubMed]
- Lee, K.; Kim, H.; Kim, J.M.; Kim, J.R.; Kim, K.J.; Kim, Y.J.; Park, S.I.; Jeong, J.H.; Moon, Y.m.; Lim, H.S. Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function. J. Cell. Mol. Med. 2011, 15, 2082–2094. [Google Scholar] [CrossRef] [PubMed]
- Cao, L.; Wang, J.; Hou, J.; Xing, W.; Liu, C. Vascularization and bone regeneration in a critical sized defect using 2-N, 6-O-sulfated chitosan nanoparticles incorporating BMP-2. Biomaterials 2014, 35, 684–698. [Google Scholar] [CrossRef] [PubMed]
- Marenzana, M.; Arnett, T.R. The key role of the blood supply to bone. Bone Res. 2013, 1, 203. [Google Scholar] [CrossRef] [PubMed]
- Rehman, J.; Traktuev, D.; Li, J.; Merfeld-Clauss, S.; Temm-Grove, C.J.; Bovenkerk, J.E.; Pell, C.L.; Johnstone, B.H.; Considine, R.V.; March, K.L. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 2004, 109, 1292–1298. [Google Scholar] [CrossRef] [PubMed]
- Kim, Y.; Kim, H.; Cho, H.; Bae, Y.; Suh, K.; Jung, J. Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia. Cell. Physiol. Biochem. 2007, 20, 867–876. [Google Scholar] [CrossRef] [PubMed]
- Hsiao, S.T.; Asgari, A.; Lokmic, Z.; Sinclair, R.; Dusting, G.J.; Lim, S.Y.; Dilley, R.J. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2012, 21, 2189–2203. [Google Scholar] [CrossRef] [PubMed]
- Peng, H.; Usas, A.; Olshanski, A.; Ho, A.M.; Gearhart, B.; Cooper, G.M.; Huard, J. VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis. J. Bone Miner. Res. 2005, 20, 2017–2027. [Google Scholar] [CrossRef] [PubMed]
- Rosen, V. BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev. 2009, 20, 475–480. [Google Scholar] [CrossRef] [PubMed]
- Biancone, L.; Bruno, S.; Deregibus, M.C.; Tetta, C.; Camussi, G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol. Dial. Transplant. 2012, 27, 3037–3042. [Google Scholar] [CrossRef] [PubMed]
- Pizzute, T.; Lynch, K.; Pei, M. Impact of tissue-specific stem cells on lineage-specific differentiation: A focus on the musculoskeletal system. Stem Cell Rev. 2015, 11, 119–132. [Google Scholar] [CrossRef] [PubMed]
- Vishnubalaji, R.; Al-Nbaheen, M.; Kadalmani, B.; Aldahmash, A.; Ramesh, T. Comparative investigation of the differentiation capability of bone-marrow- and adipose-derived mesenchymal stem cells by qualitative and quantitative analysis. Cell Tissue Res. 2012, 347, 419–427. [Google Scholar] [CrossRef] [PubMed]
- Monaco, E.; Bionaz, M.; Rodriguez-Zas, S.; Hurley, W.L.; Wheeler, M.B. Transcriptomics comparison between porcine adipose and bone marrow mesenchymal stem cells during in vitro osteogenic and adipogenic differentiation. PLoS ONE 2012, 7, e32481. [Google Scholar] [CrossRef] [PubMed]
- Shafiee, A.; Seyedjafari, E.; Soleimani, M.; Ahmadbeigi, N.; Dinarvand, P.; Ghaemi, N. A comparison between osteogenic differentiation of human unrestricted somatic stem cells and mesenchymal stem cells from bone marrow and adipose tissue. Biotechnol. Lett. 2011, 33, 1257–1264. [Google Scholar] [CrossRef] [PubMed]
- Follmar, K.; Decroos, F.; Prichard, H.; Wang, H.; Erdmann, D.; Olbrich, K. Effects of glutamine, glucose, and oxygen concentration on the metabolism and proliferation of rabbit adipose-derived stem cells. Tissue Eng. 2006, 12, 3525–3533. [Google Scholar] [CrossRef] [PubMed]
- Thangarajah, H.; Vial, I.N.; Chang, E.; El-Ftesi, S.; Januszyk, M.; Chang, E.I.; Paterno, J.; Neofytou, E.; Longaker, M.T.; Gurtner, G.C. IFATS collection: Adipose stromal cells adopt a proangiogenic phenotype under the influence of hypoxia. Stem Cells 2009, 27, 266–274. [Google Scholar] [CrossRef] [PubMed]
- Hankenson, K.D.; Dishowitz, M.; Gray, C.; Schenker, M. Angiogenesis in bone regeneration. Injury 2011, 42, 556–561. [Google Scholar] [CrossRef] [PubMed]
- Liu, Q.; Cen, L.; Zhou, H.; Yin, S.; Liu, G.; Liu, W.; Cao, Y.; Cui, L. The role of the extracellular signal-related kinase signaling pathway in osteogenic differentiation of human adipose-derived stem cells and in adipogenic transition initiated by dexamethasone. Tissue Eng. Part A 2009, 15, 3487–3497. [Google Scholar] [CrossRef] [PubMed]
- Cho, H.H.; Shin, K.K.; Kim, Y.J.; Song, J.S.; Kim, J.M.; Bae, Y.C.; Kim, C.D.; Jung, J.S. NF-κB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression. J. Cell. Physiol. 2010, 223, 168–177. [Google Scholar] [PubMed]
- Hess, K.; Ushmorov, A.; Fiedler, J.; Brenner, R.E.; Wirth, T. TNFα promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-κB signaling pathway. Bone 2009, 45, 367–376. [Google Scholar] [CrossRef] [PubMed]
- Lough, D.M.; Chambers, C.; Germann, G.; Bueno, R.; Reichensperger, J.; Swanson, E.; Dyer, M.; Cox, L.; Harrison, C.; Neumeister, M.W. Regulation of ADSC osteoinductive potential using notch pathway inhibition and gene rescue: A potential on/off switch for clinical applications in bone formation and reconstructive efforts. Plast. Reconstr. Surg. 2016, 138, 642e–652e. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Zheng, W.; Gao, W.; Shen, Y.; Ding, W. Function of TGF-beta and p38 MAKP signaling pathway in osteoblast differentiation from rat adipose-derived stem cells. Eur. Rev. Med. Pharmacol. Sci. 2013, 17, 1611–1619. [Google Scholar] [PubMed]
- Samartzis, D.; Khanna, N.; Shen, F.H.; An, H.S. Update on bone morphogenetic proteins and their application in spine surgery1. J. Am. Coll. Surg. 2005, 200, 236–248. [Google Scholar] [CrossRef] [PubMed]
- Prockop, D. “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin. Pharmacol. Ther. 2007, 82, 241–243. [Google Scholar] [CrossRef] [PubMed]
- Aulino, P.; Costa, A.; Chiaravalloti, E.; Perniconi, B.; Adamo, S.; Coletti, D.; Marrelli, M.; Tatullo, M.; Teodori, L. Muscle extracellular matrix scaffold is a multipotent environment. Int. J. Med. Sci. 2015, 12, 336. [Google Scholar] [CrossRef] [PubMed]
- Tatullo, M.; Falisi, G.; Amantea, M.; Rastelli, C.; Paduano, F.; Marrelli, M. Dental pulp stem cells and human periapical cyst mesenchymal stem cells in bone tissue regeneration: Comparison of basal and osteogenic differentiated gene expression of a newly discovered mesenchymal stem cell lineage. J. Biol. Regul. Homeost. Agents 2015, 29, 713–718. [Google Scholar] [PubMed]
- Marrelli, M.; Paduano, F.; Tatullo, M. Human periapical cyst–mesenchymal stem cells differentiate into neuronal cells. J. Dent. Res. 2015, 94, 843–852. [Google Scholar] [CrossRef] [PubMed]
- Paduano, F.; Marrelli, M.; White, L.J.; Shakesheff, K.M.; Tatullo, M. Odontogenic differentiation of human dental pulp stem cells on hydrogel scaffolds derived from decellularized bone extracellular matrix and collagen type I. PLoS ONE 2016, 11, e0148225. [Google Scholar] [CrossRef] [PubMed]
- Paduano, F.; Marrelli, M.; Alom, N.; Amer, M.; White, L.J.; Shakesheff, K.M.; Tatullo, M. Decellularized bone extracellular matrix and human dental pulp stem cells as a construct for bone regeneration. J. Biomater. Sci. Polym. Ed. 2017, 28, 730–748. [Google Scholar] [CrossRef] [PubMed]
- Tobita, M.; Orbay, H.; Mizuno, H. Adipose-derived stem cells: Current findings and future perspectives. Discov. Med. 2011, 11, 160–170. [Google Scholar] [PubMed]
- De Ugarte, D.A.; Morizono, K.; Elbarbary, A.; Alfonso, Z.; Zuk, P.A.; Zhu, M.; Dragoo, J.L.; Ashjian, P.; Thomas, B.; Benhaim, P.; et al. Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 2003, 174, 101–109. [Google Scholar] [CrossRef] [PubMed]
- Cowan, C.M.; Shi, Y.Y.; Aalami, O.O.; Chou, Y.F.; Mari, C.; Thomas, R.; Quarto, N.; Contag, C.H.; Wu, B.; Longaker, M.T. Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat. Biotechnol. 2004, 22, 560–567. [Google Scholar] [CrossRef] [PubMed]
- Grayson, W.L.; Bunnell, B.A.; Martin, E.; Frazier, T.; Hung, B.P.; Gimble, J.M. Stromal cells and stem cells in clinical bone regeneration. Nat. Rev. Endocrinol. 2015, 11, 140–150. [Google Scholar] [CrossRef] [PubMed]
- Tatullo, M.; Marrelli, M.; Amantea, M.; Paduano, F.; Santacroce, L.; Gentile, S.; Scacco, S. Bioimpedance detection of oral lichen planus used as preneoplastic model. J. Cancer 2015, 6, 976–983. [Google Scholar] [CrossRef] [PubMed]
- Marrelli, M.; Tatullo, M. Influence of PRF in the healing of bone and gingival tissues. Clinical and histological evaluations. Eur. Rev. Med. Pharmacol. Sci. 2013, 17, 1958–1962. [Google Scholar] [PubMed]
- Perniconi, B.; Coletti, D.; Aulino, P.; Costa, A.; Aprile, P.; Santacroce, L.; Chiaravalloti, E.; Coquelin, L.; Chevallier, N.; Teodori, L.; et al. Muscle acellular scaffold as a biomaterial: Effects on C2C12 cell differentiation and interaction with the murine host environment. Front. Physiol. 2014, 5, 354. [Google Scholar] [CrossRef] [PubMed]
- Mele, L.; Vitiello, P.P.; Tirino, V.; Paino, F.; De Rosa, A.; Liccardo, D.; Papaccio, G.; Desiderio, V. Changing paradigms in cranio-facial regeneration: Current and new strategies for the activation of endogenous stem cells. Front. Physiol. 2016, 7, 62. [Google Scholar] [CrossRef] [PubMed]
Clinical Trials
- US National Library of Medicine: ClinicalTrials.gov. Available online: https://clinicaltrials.gov/ct2/show/NCT02153268?term=NCT02153268&rank=1 (accessed on 3 July 2017)
- US National Library of Medicine: ClinicalTrials.gov: Available online: https://clinicaltrials.gov/ct2/show/NCT02842619?term=NCT02842619&rank=1 (accessed on 3 July 2017)
Ref. | Study | Year | Disease | Scaffolds | Affiliation | Results | Authors |
---|---|---|---|---|---|---|---|
[14] | Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report | 2004 | Calvarial fractures | Milled Bone from iliac crest with autologous Fibrin glue | Germany Justus-Liebig-University Medical School, Giessen | New bone formation and complete calvarial continuity after reconstruction | Lendeckel, S.; Jodicke, A.; Christophis, P.; Heidinger, K.; Wolff, J.; Fraser, J.K.; Hedrick, M.H.; Berthold, L.; Howaldt, H.P. |
[15] | Novel maxillary reconstruction with ectopic bone formation by GMP adipose-derived stem cells | 2009 | Hemimaxillectomy due to a large keratocyst | β-TCP and BMP-2 | Finland University of Tampere Helsinki University | Production of ectopic bone using auto ASC | Mesimaki, K.; Lindroos, B.; Tornwall, J.; Mauno, J.; Lindqvist, C.; Kontio, R.; Miettinen, S.; Suuronen, R. |
[7] | Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction | 2011 | Cranial defect | β-TCP granules | Finland Tampere University Hospital | Satisfactory outcomes in ossification | Thesleff, T.; Lehtimaki, K.; Niskakangas, T.; Mannerstrom, B.; Miettinen, S.; Suuronen, R.; Ohman, J. |
[16] | Tissue engineering of bone: Clinical observations with adipose-derived stem cells, resorbable scaffolds, and growth factors | 2012 | Large craniofacial osseous defects | Resorbable scaffolds combined with rhBMP-2 | Finland University of Tampere | Successful reconstruction of jaws, expect 3 failures | Sandor, G.K. |
[19] | Adipose-derived stem cell (ASC) tissue engineered construct used to treat large anterior mandibular defect: A case report and review of the clinical application of GMP-level ASCs for bone regeneration | 2013 | Large anterior mandibular defects (left after tumour excision) | Titanium mesh filled with β-TCP granules and BMP-2 | Finland University of Tampere University of Oulu Central Hospital of Central Finland Health Care District, Jyvaskyla, Finland | Mandibular reconstruction using the approach of in situ ossification with GMP-level ASCs | Sandor, G.K.; Tuovinen, V.J.; Wolff, J.; Patrikoski, M.; Jokinen, J.; Nieminen, E.; Mannerstrom, B.; Lappalainen, O.P.; Seppanen, R.; Miettinen, S. |
[18] | GMP-level adipose-derived stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: Experience with 3 cases | 2013 | Three mandibular ameloblastoma resection defects | Β-TCP granules | Finland University of Tampere University of Oulu Central Hospital of Central Finland Health Care District, Jyvaskyla, Finland | Reconstruction of the three mandibular defects | Wolff, J.; Sandor, G.K.; Miettinen, A.; Tuovinen, V.J.; Mannerstrom, B.; Patrikoski, M.; Miettinen, S. |
[17] | Adipose-derived Stem Cells Used to Reconstruct 13 Cases with Cranio-Maxillofacial Hard-Tissue Defects | 2014 | Cranio-maxillofacial defects: frontal sinus (3 cases); cranial bone (5 cases); mandible (3 cases); nasal septum (2 cases) | Bioactive glass granules (BAG); β-TCP granules; β-TCP strips; BMP-2 | Finland University of Tampere University of Oulu Central Hospital of Central Finland Health Care District, Jyvaskyla, Finland | Successful integration of the construct to the surrounding skeleton (10/13 cases) | Sandor, G.K.; Numminen, J.; Wolff, J.; Thesleff, T.; Miettinen, A.; Tuovinen, V.J.; Mannerstrom, B.; Patrikoski, M.; Seppanen, R.; Miettinen, S.; et al. |
No. | Clinical Trials | Clinical Trials Number (Clinicaltrials.gov) | Disease/Condition | Scaffolds | Phase | Status | Affiliation | ASC-Administration | Enrolment |
---|---|---|---|---|---|---|---|---|---|
1 | Filling Bone Defects/Voids with Autologous BonoFill For Maxillofacial Bone Regeneration | NCT02153268 link to clincialtrials.gov | Grafting after removal of cysts from jaws | OraGraft® mineral particles (Bonofill) | I/II | Completed | Kfar Saba, Israel | Autologous ASCs combined with OraGraft® mineral particles (Bonofill) Implantation of BonoFill to the maxillary or mandible defect/void | 20 |
2 | Filling Bone Defects/Voids With Autologous BonoFill-II for Maxillofacial Bone Regeneration | NCT02842619 link to clinicaltrials.gov | (1) Bone augmentation (Sinus augmentation) (2) Bone grafting after removal of cysts from jaws | OraGraft® mineral particles (Bonofill) | I/II | This study is currently recruiting participants | Kfar Saba, Israel (Oral and Maxillofacial Surgery Clinic—Beit Merik) | Autologous ASCs combined with OraGraft® mineral particles (Bonofill) Transplantation of BonoFill-II to the maxillary or mandible defect/void | 20 |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Paduano, F.; Marrelli, M.; Amantea, M.; Rengo, C.; Rengo, S.; Goldberg, M.; Spagnuolo, G.; Tatullo, M. Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications. Int. J. Mol. Sci. 2017, 18, 2140. https://doi.org/10.3390/ijms18102140
Paduano F, Marrelli M, Amantea M, Rengo C, Rengo S, Goldberg M, Spagnuolo G, Tatullo M. Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications. International Journal of Molecular Sciences. 2017; 18(10):2140. https://doi.org/10.3390/ijms18102140
Chicago/Turabian StylePaduano, Francesco, Massimo Marrelli, Massimiliano Amantea, Carlo Rengo, Sandro Rengo, Michel Goldberg, Gianrico Spagnuolo, and Marco Tatullo. 2017. "Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications" International Journal of Molecular Sciences 18, no. 10: 2140. https://doi.org/10.3390/ijms18102140