Facial Plast Surg 2010; 26(5): 385-395
DOI: 10.1055/s-0030-1265017
© Thieme Medical Publishers

Clinical Applications of Stem Cells in Craniofacial Surgery

Christopher M. Runyan1 , Jesse A. Taylor1
  • 1Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Further Information

Publication History

Publication Date:
17 September 2010 (online)

ABSTRACT

Few areas of translational medicine carry as much excitement and hope as stem cell therapies. Because of recent advances in material science and stem cell and developmental biology that help to target molecules and pathways to restore the body's regenerative capacity, the “engineering” of missing tissue is quickly becoming a reality. Classically, tissue engineering has been thought to require external regenerative resources including a scaffold, cells, and growth factors. The allure of providing an exact replica of a missing bone that incorporates to become indistinguishable from self, has the capacity to heal and grow, is resistant to infection, and has minimal morbidity is a “holy grail” to all surgeons who work with bone. This article attempts to shed light on the use of stem cells for craniofacial reconstruction, including important principles learned from other scientific disciplines, relevant animal models for tissue engineering, early clinical reports from our experience and that of others, and future directions.

REFERENCES

  • 1 Thomson J A, Itskovitz-Eldor J, Shapiro S S et al.. Embryonic stem cell lines derived from human blastocysts.  Science. 1998;  282 1145-1147
  • 2 National Institutes of Health. ClinicalTrials.gov. Available at: http://clinicaltrials.gov/ct/search?term=stem+cell Accessed July 28, 2010
  • 3 Takahashi K, Tanabe K, Ohnuki M et al.. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.  Cell. 2007;  131 861-872
  • 4 Wernig M, Meissner A, Foreman R et al.. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.  Nature. 2007;  448 318-324
  • 5 Chin M H, Mason M J, Xie W et al.. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.  Cell Stem Cell. 2009;  5 111-123
  • 6 Feng Q, Lu S J, Klimanskaya I et al.. Hemangioblastic derivatives from human induced pluripotent stem cells exhibit limited expansion and early senescence.  Stem Cells. 2010;  28 704-712
  • 7 Reynolds B A, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.  Science. 1992;  255 1707-1710
  • 8 Toma J G, Akhavan M, Fernandes K J et al.. Isolation of multipotent adult stem cells from the dermis of mammalian skin.  Nat Cell Biol. 2001;  3 778-784
  • 9 Wada M R, Inagawa-Ogashiwa M, Shimizu S, Yasumoto S, Hashimoto N. Generation of different fates from multipotent muscle stem cells.  Development. 2002;  129 2987-2995
  • 10 Conrad S, Renninger M, Hennenlotter J et al.. Generation of pluripotent stem cells from adult human testis.  Nature. 2008;  456 344-349
  • 11 Zuk P A, Zhu M, Mizuno H et al.. Multilineage cells from human adipose tissue: implications for cell-based therapies.  Tissue Eng. 2001;  7 211-228
  • 12 Zuk P A, Zhu M, Ashjian P et al.. Human adipose tissue is a source of multipotent stem cells.  Mol Biol Cell. 2002;  13 4279-4295
  • 13 Friedenstein A J, Piatetzky-Shapiro I I, Petrakova K V. Osteogenesis in transplants of bone marrow cells.  J Embryol Exp Morphol. 1966;  16 381-390
  • 14 Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells.  J Clin Invest. 2010;  120 51-59
  • 15 Stephenson E L, Mason C, Braude P R. Preimplantation genetic diagnosis as a source of human embryonic stem cells for disease research and drug discovery.  BJOG. 2009;  116 158-165
  • 16 Linke A, Müller P, Nurzynska D et al.. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.  Proc Natl Acad Sci U S A. 2005;  102 8966-8971
  • 17 Dawn B, Stein A B, Urbanek K et al.. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function.  Proc Natl Acad Sci U S A. 2005;  102 3766-3771
  • 18 Wernig M, Zhao J P, Pruszak J et al.. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease.  Proc Natl Acad Sci U S A. 2008;  105 5856-5861
  • 19 Xu D, Alipio Z, Fink L M et al.. Phenotypic correction of murine hemophilia A using an iPS cell-based therapy.  Proc Natl Acad Sci U S A. 2009;  106 808-813
  • 20 Hanna J, Wernig M, Markoulaki S et al.. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin.  Science. 2007;  318 1920-1923
  • 21 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998–2007. Rockville, MD; Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation Richmond, VA; United Network for Organ Sharing Ann Arbor, MI; University Renal Research and Education Association 2007
  • 22 Atala A. Engineering organs.  Curr Opin Biotechnol. 2009;  20 575-592
  • 23 Levenberg S, Huang N F, Lavik E, Rogers A B, Itskovitz-Eldor J, Langer R. Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds.  Proc Natl Acad Sci U S A. 2003;  100 12741-12746
  • 24 Taylor D A. From stem cells and cadaveric matrix to engineered organs.  Curr Opin Biotechnol. 2009;  20 598-605
  • 25 Macchiarini P, Jungebluth P, Go T et al.. Clinical transplantation of a tissue-engineered airway.  Lancet. 2008;  372 2023-2030
  • 26 Bhatt A, Le Anh D. Craniofacial tissue regeneration: where are we?.  J Calif Dent Assoc. 2009;  37 799-803
  • 27 Zaky S H, Cancedda R. Engineering craniofacial structures: facing the challenge.  J Dent Res. 2009;  88 1077-1091
  • 28 Zuk P A. Tissue engineering craniofacial defects with adult stem cells? Are we ready yet?.  Pediatr Res. 2008;  63 478-486
  • 29 Pittenger M F, Mackay A M, Beck S C et al.. Multilineage potential of adult human mesenchymal stem cells.  Science. 1999;  284 143-147
  • 30 Dragoo J L, Choi J Y, Lieberman J R et al.. Bone induction by BMP-2 transduced stem cells derived from human fat.  J Orthop Res. 2003;  21 622-629
  • 31 De Ugarte D A, Morizono K, Elbarbary A et al.. Comparison of multi-lineage cells from human adipose tissue and bone marrow.  Cells Tissues Organs. 2003;  174 101-109
  • 32 Panetta N J, Gupta D M, Lee J K, Wan D C, Commons G W, Longaker M T. Human adipose-derived stromal cells respond to and elaborate bone morphogenetic protein-2 during in vitro osteogenic differentiation.  Plast Reconstr Surg. 2010;  125 483-493
  • 33 Peterson B, Zhang J, Iglesias R et al.. Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue.  Tissue Eng. 2005;  11 120-129
  • 34 Seto I, Marukawa E, Asahina I. Mandibular reconstruction using a combination graft of rhBMP-2 with bone marrow cells expanded in vitro.  Plast Reconstr Surg. 2006;  117 902-908
  • 35 Chang S C, Chuang H, Chen Y R et al.. Cranial repair using BMP-2 gene engineered bone marrow stromal cells.  J Surg Res. 2004;  119 85-91
  • 36 Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao R C. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo.  Biochem Biophys Res Commun. 2005;  332 370-379
  • 37 Scherberich A, Galli R, Jaquiery C, Farhadi J, Martin I. Three-dimensional perfusion culture of human adipose tissue-derived endothelial and osteoblastic progenitors generates osteogenic constructs with intrinsic vascularization capacity.  Stem Cells. 2007;  25 1823-1829
  • 38 Neufeld G, Kessler O, Vadasz Z, Gluzman-Poltorak Z. The contribution of proangiogenic factors to the progression of malignant disease: role of vascular endothelial growth factor and its receptors.  Surg Oncol Clin N Am. 2001;  10 339-356, ix
  • 39 Kirker-Head C A. Development and application of bone morphogenetic proteins for the enhancement of bone healing.  J Orthop Traumatol. 2005;  6 1-9
  • 40 Mikroulis D, Papanas N, Maltezos E, Bougioukas G. Angiogenic growth factors in the treatment of peripheral arterial disease.  Curr Vasc Pharmacol. 2007;  5 195-209
  • 41 Gitelis S, Wilkins R M, Yasko A W. BMPs and cancer: Is the risk real? AAOS Now. Available at: http://www.aaos.org/news/aaosnow/may08/research7.asp Accessed July 28, 2010
  • 42 Bueno E M, Glowacki J. Cell-free and cell-based approaches for bone regeneration.  Nat Rev Rheumatol. 2009;  5 685-697
  • 43 Cancedda R, Giannoni P, Mastrogiacomo M. A tissue engineering approach to bone repair in large animal models and in clinical practice.  Biomaterials. 2007;  28 4240-4250
  • 44 Hutmacher D W, Schantz J T, Lam C X, Tan K C, Lim T C. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective.  J Tissue Eng Regen Med. 2007;  1 245-260
  • 45 Yoon E, Dhar S, Chun D E, Gharibjanian N A, Evans G R. In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model.  Tissue Eng. 2007;  13 619-627
  • 46 Smith D M, Afifi A M, Cooper G M, Mooney M P, Marra K G, Losee J E. BMP-2-based repair of large-scale calvarial defects in an experimental model: regenerative surgery in cranioplasty.  J Craniofac Surg. 2008;  19 1315-1322
  • 47 Sawyer A A, Song S J, Susanto E et al.. The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2.  Biomaterials. 2009;  30 2479-2488
  • 48 Taub P J, Yau J, Spangler M, Mason J M, Lucas P A. Bioengineering of calvaria with adult stem cells.  Plast Reconstr Surg. 2009;  123 1178-1185
  • 49 Park J W, Jang J H, Bae S R, An C H, Suh J Y. Bone formation with various bone graft substitutes in critical-sized rat calvarial defect.  Clin Oral Implants Res. 2009;  20 372-378
  • 50 Bohnenblust M E, Steigelman M B, Wang Q, Walker J A, Wang H T. An experimental design to study adipocyte stem cells for reconstruction of calvarial defects.  J Craniofac Surg. 2009;  20 340-346
  • 51 Meijer G J, de Bruijn J D, Koole R, van Blitterswijk C A. Cell-based bone tissue engineering.  PLoS Med. 2007;  4 e9
  • 52 Lendeckel S, Jödicke A, Christophis P et al.. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report.  J Craniomaxillofac Surg. 2004;  32 370-373
  • 53 He Y, Zhang Z Y, Zhu H G, Qiu W, Jiang X, Guo W. Experimental study on reconstruction of segmental mandible defects using tissue engineered bone combined bone marrow stromal cells with three-dimensional tricalcium phosphate.  J Craniofac Surg. 2007;  18 800-805
  • 54 Yuan J, Cui L, Zhang W J, Liu W, Cao Y. Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate.  Biomaterials. 2007;  28 1005-1013
  • 55 Abukawa H, Shin M, Williams W B, Vacanti J P, Kaban L B, Troulis M J. Reconstruction of mandibular defects with autologous tissue-engineered bone.  J Oral Maxillofac Surg. 2004;  62 601-606
  • 56 Marukawa E, Asahina I, Oda M, Seto I, Alam M, Enomoto S. Functional reconstruction of the non-human primate mandible using recombinant human bone morphogenetic protein-2.  Int J Oral Maxillofac Surg. 2002;  31 287-295
  • 57 Carstens M H, Chin M, Li X J. In situ osteogenesis: regeneration of 10-cm mandibular defect in porcine model using recombinant human bone morphogenetic protein-2 (rhBMP-2) and Helistat absorbable collagen sponge.  J Craniofac Surg. 2005;  16 1033-1042
  • 58 Seto I, Asahina I, Oda M, Enomoto S. Reconstruction of the primate mandible with a combination graft of recombinant human bone morphogenetic protein-2 and bone marrow.  J Oral Maxillofac Surg. 2001;  59 53-61; discussion 62–63
  • 59 Warnke P H, Springer I N, Wiltfang J et al.. Growth and transplantation of a custom vascularised bone graft in a man.  Lancet. 2004;  364 766-770
  • 60 Warnke P H, Wiltfang J, Springer I et al.. Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible.  Biomaterials. 2006;  27 3163-3167
  • 61 Chao M, Donovan T, Sotelo C, Carstens M H. In situ osteogenesis of hemimandible with rhBMP-2 in a 9-year-old boy: osteoinduction via stem cell concentration.  J Craniofac Surg. 2006;  17 405-412
  • 62 Herford A S, Boyne P J. Reconstruction of mandibular continuity defects with bone morphogenetic protein-2 (rhBMP-2).  J Oral Maxillofac Surg. 2008;  66 616-624
  • 63 Enneking W F, Mindell E R. Observations on massive retrieved human allografts.  J Bone Joint Surg Am. 1991;  73 1123-1142
  • 64 Enneking W F, Campanacci D A. Retrieved human allografts: a clinicopathological study.  J Bone Joint Surg Am. 2001;  83 971-986
  • 65 Wheeler D L, Enneking W F. Allograft bone decreases in strength in vivo over time.  Clin Orthop Relat Res. 2005;  435 36-42
  • 66 Follmar K E, Prichard H L, DeCroos F C et al.. Combined bone allograft and adipose-derived stem cell autograft in a rabbit model.  Ann Plast Surg. 2007;  58 561-565
  • 67 Grayson W L, Frohlich M, Yeager K et al.. Engineering anatomically shaped human bone grafts.  Proc Natl Acad Sci U S A. 2010;  107 3299-3304
  • 68 Ito H, Koefoed M, Tiyapatanaputi P et al.. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy.  Nat Med. 2005;  11 291-297
  • 69 Runyan C M, Jones D C, Bove K E, Maercks R A, Simpson D S, Taylor J A. Porcine allograft mandible revitalization using autologous adipose-derived stem cells, bone morphogenetic protein-2, and periosteum.  Plast Reconstr Surg. 2010;  125 1372-1382
  • 70 Fiedler J, Röderer G, Günther K P, Brenner R E. BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells.  J Cell Biochem. 2002;  87 305-312
  • 71 Hutmacher D W, Sittinger M. Periosteal cells in bone tissue engineering.  Tissue Eng. 2003;  9(Suppl 1) S45-S64
  • 72 Zhang X, Xie C, Lin A S et al.. Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering.  J Bone Miner Res. 2005;  20 2124-2137
  • 73 Zhang X, Awad H A, O'Keefe R J, Guldberg R E, Schwarz E M. A perspective: engineering periosteum for structural bone graft healing.  Clin Orthop Relat Res. 2008;  466 1777-1787
  • 74 Kosnik E J, Sayers M P. Congenital scalp defects: aplasia cutis congenita.  J Neurosurg. 1975;  42 32-36
  • 75 Moscona R, Berger J, Govrin J. Large skull defect in aplasia cutis congenita treated by pericranial flap: long-term follow-up.  Ann Plast Surg. 1991;  26 178-182
  • 76 Skoog T. The use of periosteal flaps in the repair of clefts of the primary palate.  Cleft Palate J. 1965;  2 332-339
  • 77 Ritsilä V, Alhopuro S, Gylling U, Rintala A. The use of free periosteum for bone formation in congenital clefts of the maxilla. A preliminary report.  Scand J Plast Reconstr Surg. 1972;  6 57-60
  • 78 Ritsilä V, Alhopuro S, Rintala A. Bone formation with free periosteal grafts in reconstruction of congenital maxillary clefts.  Ann Chir Gynaecol. 1976;  65 342-344
  • 79 Kelley P, Klebuc M, Hollier L. Complex midface reconstruction: maximizing contour and bone graft survival utilizing periosteal free flaps.  J Craniofac Surg. 2003;  14 779-782
  • 80 Satoh T, Tsuchiya M, Harii K. A vascularised iliac musculo-periosteal free flap transfer: a case report.  Br J Plast Surg. 1983;  36 109-112
  • 81 Crock J G, Morrison W A. A vascularised periosteal flap: anatomical study.  Br J Plast Surg. 1992;  45 474-478
  • 82 Finley J M, Acland R D, Wood M B. Revascularized periosteal grafts—a new method to produce functional new bone without bone grafting.  Plast Reconstr Surg. 1978;  61 1-6
  • 83 Acland R D. Caution about clinical use of vascularized periosteal grafts.  Plast Reconstr Surg. 1978;  62 290
  • 84 Burstein F D, Canalis R F. Studies on the osteogenic potential of vascularized periosteum: behavior of periosteal flaps transferred onto soft tissues.  Otolaryngol Head Neck Surg. 1985;  93 731-735
  • 85 Romana M C, Masquelet A C. Vascularized periosteum associated with cancellous bone graft: an experimental study.  Plast Reconstr Surg. 1990;  85 587-592
  • 86 Xie C, Reynolds D, Awad H et al.. Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering.  Tissue Eng. 2007;  13 435-445
  • 87 Warnke P H, Douglas T, Sivananthan S, Wiltfang J, Springer I, Becker S T. Tissue engineering of periosteal cell membranes in vitro.  Clin Oral Implants Res. 2009;  20 761-766
  • 88 Maercks R A, Runyan C M, Jones D C, Taylor J A. The vastus intermedius periosteal (VIP) flap: a novel flap for osteoinduction.  J Reconstr Microsurg. 2010;  26 335-340

Jesse A TaylorM.D. 

Assistant Professor, Division of Plastic and Reconstructive Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center

3333 Burnet Avenue, ML 2020, Cincinnati, OH 45229

Email: jataylor@gmail.com

    >