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Enhance Mandibular Symphyseal Surface Bone Growth with Autologous Mesenchymal Stem Cell Sheets: An Animal Study

  • Lei Shi
  • Boon Ching Tee
  • Leighann Cotter
  • Zongyang SunEmail author
Original Paper Basic science/Experimental
  • 30 Downloads

Abstract

Introduction

The size and shape of the chin strongly influence facial profile and harmony. The current correction of chin deficiency mostly relies on genioplasty surgery involving osteotomy. To avoid osteotomy, one possible alternative is to enhance bone growth at the mental protuberance area with cell sheet transplantation. This study was undertaken to evaluate the efficacy of this approach in a pig model.

Materials and Methods

Five 4-month-old pigs were included for mandibular bone marrow aspiration and MSC isolation. Triple-layer MSC sheets were then fabricated and utilized using culture-expanded MSCs. Four weeks after bone marrow aspiration, subperiosteal pockets were created on the labial symphyseal surface, followed by transplantation of autogenous MSC sheets to one randomly chosen side with the other side (control) receiving no transplantation. Six weeks after the surgery, the pigs were euthanized and the specimens from both sides were collected for computed tomography (CT) and histological and immunohistochemical analysis. Measurements between the experimental and control sides were compared using paired t tests.

Results

MSC sheet fabrication and transplantation were reliably conducted. The labial cortical bone thickness increased significantly with MSC sheet transplantation by an average of 2 mm (p = 0.0001). The average measurements of mineral apposition rate and cell proliferation at the cell sheet side tended to be higher than the control side although the differences did not reach statistical significance (p = 0.1–0.2). Tissue mineral density measurements from CT images and bone volume fraction (BV/TV) measurements from histologic images were identical between the two sides (p > 0.5).

Conclusion

These data provide a proof of concept that autologous MSC sheets may be transplanted to the subperiosteal region of the mandibular symphysis to stimulate local surface bone growth.

No Level Assigned

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Keywords

Chin deficiency Mesenchymal stem cells Bone growth Cell sheets Pig 

Notes

Acknowledgements

LS contributed to data acquisition, analysis and interpretation, manuscript drafting and revision; BCT contributed to study design, data acquisition and statistical analysis; LC contributed to data acquisition, analysis and interpretation; ZS contributed to study conception and design, statistical analysis, data interpretation and critical manuscript revision.

Funding

The study was funded by the American Association of Orthodontists Foundation.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest.

Ethical Approval

All applicable institutional and national guidelines for the care and use of animals were followed.

Informed Consent

For this type of study, informed consent is not required.

References

  1. 1.
    Bertossi D, Galzignato PF, Albanese M, Botti C, Botti G, Nocini PF (2015) Chin microgenia: a clinical comparative study. Aesthetic Plast Surg 39:651–658CrossRefPubMedGoogle Scholar
  2. 2.
    Chang CS, Kang GCW (2016) Achieving ideal lower face aesthetic contours: combination of tridimensional fat grafting to the chin with masseter botulinum toxin injection. Aesthetic Surg J 36:1093–1100CrossRefGoogle Scholar
  3. 3.
    Aston SJ, Smith DM (2015) Taking it on the chin: recognizing and accounting for lower face asymmetry in chin augmentation and genioplasty. Plast Reconstr Surg 135:1591–1595CrossRefPubMedGoogle Scholar
  4. 4.
    Ricketts RM (1982) Divine proportion in facial esthetics. Clin Plast Surg 9:401–422PubMedGoogle Scholar
  5. 5.
    Enlow DH (1996) Essentials of facial growth. Saunders, PhiladelphiaGoogle Scholar
  6. 6.
    Ochareon P, Herring SW (2007) Growing the mandible: role of the periosteum and its cells. Anat Rec Hoboken 290:1366–1376CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    White JB, Dufresne CR (2011) Management and avoidance of complications in chin augmentation. Aesthet Surg J 31:634–642CrossRefPubMedGoogle Scholar
  8. 8.
    Lowe NJ, Maxwell CA, Patnaik R (2005) Adverse reactions to dermal fillers: review. Dermatol Surg 31:1616–1625PubMedGoogle Scholar
  9. 9.
    Van Sickels JE, Tiner BD (1992) Cost of a genioplasty under deep intravenous sedation in a private office versus general anesthesia in an outpatient surgical center. J Oral Maxillofac Surg 50:687–690CrossRefPubMedGoogle Scholar
  10. 10.
    Ho-Shui-Ling A, Bolander J, Rustom LE, Johnson AW, Luyten FP, Picart C (2018) Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials 180:143–162CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ueno T, Kagawa T, Fukunaga J, Mizukawa N, Kanou M, Fujii T, Sugahara T, Yamamoto T (2003) Regeneration of the mandibular head from grafted periosteum. Ann Plast Surg 51:77–83CrossRefPubMedGoogle Scholar
  12. 12.
    Ueno T, Kagawa T, Ishida N, Fukunaga J, Mizukawa N, Sugahara T, Yamamoto T (2001) Prefabricated bone graft induced from grafted periosteum for the repair of jaw defects: an experimental study in rabbits. J Cranio-Maxillofac Surg 29:219–223CrossRefGoogle Scholar
  13. 13.
    Reinholz GG, Fitzsimmons JS, Casper ME, Ruesink TJ, Chung HW, Schagemann JC, Odriscoll SW (2009) Rejuvenation of periosteal chondrogenesis using local growth factor injection. Osteoarthr Cartil 17:723–734CrossRefPubMedGoogle Scholar
  14. 14.
    Patil AS, Sable RB, Kothari RM (2011) An update on transforming growth factor-β (TGF-β): sources, types, functions and clinical applicability for cartilage/bone healing. J Cell Physiol 226:3094–3103CrossRefPubMedGoogle Scholar
  15. 15.
    Schonmeyr B, Clavin N, Avraham T, Longo V, Mehrara BJ (2009) Synthesis of a tissue-engineered periosteum with acellular dermal matrix and cultured mesenchymal stem cells. Tissue Eng Part A 15:1833–1841CrossRefPubMedGoogle Scholar
  16. 16.
    Xie C, Reynolds D, Awad H, Rubery PT, Pelled G, Gazit D, Guldberg RE, Schwarz EM, Okeefe RJ, Zhang X (2007) Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering. Tissue Eng 13:435–445CrossRefPubMedGoogle Scholar
  17. 17.
    Sun Z, Tee BC, Kennedy KS, Kennedy PM, Kim DG, Mallery SR, Fields HW (2013) Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model. PLoS ONE 8:74672CrossRefGoogle Scholar
  18. 18.
    Ma D, Zhong C, Yao H, Liu Y, Chen F, Li J, Zhao J, Mao T, Ren L (2011) Engineering injectable bone using bone marrow stromal cell aggregates. Stem Cells Dev 20:989–999CrossRefPubMedGoogle Scholar
  19. 19.
    Fernandes MBC, Guimarães JA, Casado P, Ados Cavalcanti, Gonçalves NN, Ambrósio CE, Rodrigues F, Pinto ACF, Miglino M, Duarte MEL (2014) The effect of bone allografts combined with bone marrow stromal cells on the healing of segmental bone defects in a sheep model. BMC Vet Res 10:36CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kitoh H, Kitakoji T, Tsuchiya H, Mitsuyama H, Nakamura H, Katoh M, Ishiguro N (2004) Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis—a preliminary result of three cases. Bone 35:892–898CrossRefPubMedGoogle Scholar
  21. 21.
    Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y (2004) Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med 351:1187–1196CrossRefGoogle Scholar
  22. 22.
    Ohki T, Yamato M, Ota M, Takagi R, Murakami D, Kondo M, Sasaki R, Namiki H, Okano T, Yamamoto M (2012) Prevention of esophageal stricture after endoscopic submucosal dissection using tissue-engineered cell sheets. Gastroenterology 143:582–588CrossRefGoogle Scholar
  23. 23.
    Sawa Y, Miyagawa S, Sakaguchi T, Fujita T, Matsuyama A, Saito A, Shimizu T, Okano T (2012) Tissue engineered myoblast sheets improved cardiac function sufficiently to discontinue LVAS in a patient with DCM: report of a case. Surg Today 42:181–184CrossRefGoogle Scholar
  24. 24.
    Iwata T, Washio K, Yoshida T, Ishikawa I, Ando T, Yamato M, Okano T (2015) Cell sheet engineering and its application for periodontal regeneration. J Tissue Eng Regen Med 9:343–356CrossRefPubMedGoogle Scholar
  25. 25.
    Mu S, Tee BC, Emam H, Zhou Y, Sun Z (2018) Culture-expanded mesenchymal stem cell sheets enhance extraction-site alveolar bone growth: an animal study. J Periodontal Res 53:514–524CrossRefPubMedGoogle Scholar
  26. 26.
    Wang Z-S, Feng Z-H, Wu G-F, Bai S-Z, Dong Y, Chen F-M, Zhao Y-M (2016) The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering. Sci Rep 6:28126CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Liang Y, Wen L, Shang F, Wu J, Sui K, Ding Y (2016) Endothelial progenitors enhanced the osteogenic capacities of mesenchymal stem cells in vitro and in a rat alveolar bone defect model. Arch Oral Biol 68:123–130CrossRefPubMedGoogle Scholar
  28. 28.
    Yu M, Zhou W, Song Y, Yu F, Li D, Na S, Zou G, Zhai M, Xie C (2011) Development of mesenchymal stem cell-implant complexes by cultured cells sheet enhances osseointegration in type 2 diabetic rat model. Bone 49:387–394CrossRefPubMedGoogle Scholar
  29. 29.
    Ueyama Y, Yagyuu T, Maeda M, Imada M, Akahane M, Kawate K, Tanaka Y, Kirita T (2016) Maxillofacial bone regeneration with osteogenic matrix cell sheets: an experimental study in rats. Arch Oral Biol 72:138–145CrossRefPubMedGoogle Scholar
  30. 30.
    Strom D, Holm S, Clemensson E, Haraldson T, Carlsson GE (1986) Gross anatomy of the mandibular joint and masticatory muscles in the domestic pig (Sus scrofa). Arch Oral Biol 31:763–768CrossRefPubMedGoogle Scholar
  31. 31.
    Price J, Tee BC, Vig K, Shanker S, Kennedy K, Sun Z (2015) Growth characteristics underlying the lack of a chin in pigs: a histomorphometric study. Orthod Craniofac Res 18:232–241CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lloyd B, Tee BC, Headley C, Emam H, Mallery S, Sun Z (2017) Similarities and differences between porcine mandibular and limb bone marrow mesenchymal stem cells. Arch Oral Biol 77:1–11CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Shudo Y, Cohen JE, Macarthur JW, Atluri P, Hsiao PF, Yang EC, Fairman AS, Trubelja A, Patel J, Miyagawa S, Sawa Y, Woo YJ (2013) Spatially oriented, temporally sequential smooth muscle cell-endothelial progenitor cell bi-level cell sheet neovascularizes ischemic myocardium. Circulation 128:S59–S68CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kaigler D, Pagni G, Park CH, Braun TM, Holman LA, Yi E, Tarle SA, Bartel RL, Giannobile WV (2013) Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial. Cell Transpl 22:767–777CrossRefGoogle Scholar
  35. 35.
    Xie J, Han Z, Naito M, Maeyama A, Kim SH, Kim YH, Matsuda T (2010) Articular cartilage tissue engineering based on a mechano-active scaffold made of poly(L-lactide-co-ε-caprolactone): in vivo performance in adult rabbits. J Biomed Mater Res Part B Appl Biomater 94:80–88PubMedGoogle Scholar
  36. 36.
    Aghaloo TL, Chaichanasakul T, Bezouglaia O, Kang B, Franco R, Dry SM, Atti E, Tetradis S (2010) Osteogenic potential of mandibular vs long-bone marrow stromal cells. J Dent Res 89:1293–1298CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dong W, Ge J, Zhang P, Fu Y, Zhang Z, Cheng J, Jiang H (2014) Phenotypic characterization of craniofacial bone marrow stromal cells: unique properties of enhanced osteogenesis, cell recruitment, autophagy, and apoptosis resistance. Cell Tissue Res 358:165–175CrossRefPubMedGoogle Scholar
  38. 38.
    Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG (2006) Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38:758–768CrossRefPubMedGoogle Scholar
  39. 39.
    Jenkins J, Shi L, Tee BC, Emam H, Larsen P, Sun Z (2019) Impact of bone marrow withdrawal on local corticotomy healing. J Dent Res 98(1):0857Google Scholar
  40. 40.
    Katagiri W, Osugi M, Kawai T, Ueda M (2013) Novel cell-free regeneration of bone using stem cell-derived growth factors. Int J Oral Maxillofac Implants 28:1009–1016CrossRefPubMedGoogle Scholar
  41. 41.
    Katagiri W, Osugi M, Kawai T, Hibi H (2016) First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med 12:5CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Frost HM (1983) The regional acceleratory phenomenon: a review. Henry Ford Hosp Med J 31:3–9PubMedGoogle Scholar
  43. 43.
    Bloebaum RD, Willie BM, Mitchell BS, Hofmann AA (2007) Relationship between bone ingrowth, mineral apposition rate, and osteoblast activity. J Biomed Mater Res A 81:505–514CrossRefPubMedGoogle Scholar
  44. 44.
    Owen KM, Campbell PM, Feng JQ, Dechow PC, Buschang PH (2017) Elevation of a full-thickness mucoperiosteal flap alone accelerates orthodontic tooth movement. Am J Orthod Dentofacial Orthop 152:49–57CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.Department of Pediatric Dentistry, Ninth People’s HospitalShanghai Jiaotong University, School of MedicineShanghaiChina
  2. 2.Division of Orthodontics, College of DentistryThe Ohio State UniversityColumbusUSA
  3. 3.Division of Biosciences, College of DentistryThe Ohio State UniversityColumbusUSA
  4. 4.College of Arts and SciencesThe Ohio State UniversityColumbusUSA

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