Abstract
Over three-quarters of all craniofacial defects observed in the US per year are cleft palates. Usually involving significant bony defects in both the hard palate and alveolar process of the maxilla, repair of these defects is typically performed surgically using autologous bone grafts taken from appropriate sites (i.e., iliac crest). However, surgical intervention is not without its complications. As such, the reconstructive surgeon has turned to the scientist and engineer for help. In this review, the application of the field of tissue engineering to craniofacial defects (e.g., cleft palates) is discussed. Specifically the use of adult stem cells, such as mesenchymal stem cells from bone marrow and Adipose-derived Stem Cells (ASCs) in combination with currently available biomaterials is presented in the context of healing craniofacial defects like the cleft palate. Finally, future directions with regards to the use of ASCs in craniofacial repair are discussed, including possible scaffold-driven and gene-driven approaches.
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Abbreviations
- ASCs:
-
Adipose-derived Stem Cells
- BMP2:
-
bone morphogenic protein 2
- DMB:
-
demineralized bone matrix
- ES cell:
-
embryonic stem cell
- HA:
-
hydroxyapatite
- MNP:
-
medial nasal process
- MSC:
-
Mesenchymal Stem Cell
- PLGA:
-
poly(lactic-co-glycolic) acid
- SVF:
-
stromo-vascular fraction
- TCP:
-
tri-calcium phosphate
References
Vanderas AP 1987 Incidence of cleft lip, cleft palate, and cleft lip and palate among races: a review. Cleft Palate J 24: 216–225
Steiner C, Elixhauser A, Schnaier J 2002 The healthcare cost and utilization project: an overview. Eff Clin Pract 5: 143–151
Witt PD, Marsh JL 1998 Cleft Palate Deformities. Stamford, CT, Appleton & Lange
Couly GF, Coltey PM, Le Douarin NM 1992 The developmental fate of the cephalic mesoderm in quail-chick chimeras. Development 114: 1–15
Noden DM 1982 Patterns and organization of craniofacial skeletogenic and myogenic mesenchyme: a perspective. Prog Clin Biol Res 101: 167–203
Trasler DG 1968 Pathogenesis of cleft lip and its relation to embryonic face shape in A-J and C57BL mice. Teratology 1: 33–49
Ferguson MW 1988 Palate development. Development 103: 41–60
Greenwald AS, Boden SD, Goldberg VM, Khan Y, Laurencin CT, Rosier RN 2001 Bone-graft substitutes: facts, fictions, and applications. J Bone Joint Surg Am 83-A: 98–103
Mulliken JB, Glowacki J 1980 Induced osteogenesis for repair and construction in the craniofacial region. Plast Reconstr Surg 65: 553–560
Herring SW, Ochareon P 2005 Bone–special problems of the craniofacial region. Orthod Craniofac Res 8: 174–182
Hylander WL, Johnson KR 1997 In vivo bone strain patterns in the zygomatic arch of macaques and the significance of these patterns for functional interpretations of craniofacial form. Am J Phys Anthropol 102: 203–232
Teng S, Herring SW 1996 Anatomic and directional variation in the mechanical properties of the mandibular condyle in pigs. J Dent Res 75: 1842–1850
Stevenson S 1998 Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin Orthop Relat Res S239–S246
Urist MR 1965 Bone: formation by autoinduction. Science 150: 893–899
LeGeros RZ 2002 Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res 81–98
Ohgushi H, Dohi Y, Tamai S, Tabata S 1993 Osteogenic differentiation of marrow stromal stem cells in porous hydroxyapatite ceramics. J Biomed Mater Res 27: 1401–1407
Kuhne JH, Bartl R, Frisch B, Hammer C, Jansson V, Zimmer M 1994 Bone formation in coralline hydroxyapatite. Effects of pore size studied in rabbits. Acta Orthop Scand 65: 246–252
Ohgushi H, Okumura M, Tamai S, Shors EC, Caplan AI 1990 Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. J Biomed Mater Res 24: 1563–1570
Toquet J, Rohanizadeh R, Guicheux J, Couillaud S, Passuti N, Daculsi G, Heymann D 1999 Osteogenic potential in vitro of human bone marrow cells cultured on macroporous biphasic calcium phosphate ceramic. J Biomed Mater Res 44: 98–108
Ioku K, Yanagisawa K, Yamasaki N, Kurosawa H, Shibuya K, Yokozeki H 1993 Preparation and characterization of porous apatite ceramics coated with beta-tricalcium phosphate. Biomed Mater Eng 3: 137–145
Goodman SB, Bauer TW, Carter D, Casteleyn PP, Goldstein SA, Kyle RF, Larsson S, Stankewich CJ, Swiontkowski MF, Tencer AF, Yetkinler DN, Poser RD 1998 Norian SRS cement augmentation in hip fracture treatment. Laboratory and initial clinical results. Clin Orthop Relat Res 42–50
Eppley BL, Hollier L, Stal S 2003 Hydroxyapatite cranioplasty: 2. Clinical experience with a new quick-setting material. J Craniofac Surg 14: 209–214
Coombes AG, Meikle MC 1994 Resorbable synthetic polymers as replacements for bone graft. Clin Mater 17: 35–67
Freed LE, Vunjak-Novakovic G, Biron RJ, Eagles DB, Lesnoy DC, Barlow SK, Langer R 1994 Biodegradable polymer scaffolds for tissue engineering. Biotechnology (NY) 12: 689–693
Abukawa H, Papadaki M, Abulikemu M, Leaf J, Vacanti JP, Kaban LB, Troulis MJ 2006 The engineering of craniofacial tissues in the laboratory: a review of biomaterials for scaffolds and implant coatings. Dent Clin North Am 50: 205–216
Eppley BL, Pietrzak WS, Blanton MW 2005 Allograft and alloplastic bone substitutes: a review of science and technology for the craniomaxillofacial surgeon. J Craniofac Surg 16: 981–989
Warejcka DJ, Harvey R, Taylor BJ, Young HE, Lucas PA 1996 A population of cells isolated from rat heart capable of differentiating into several mesodermal phenotypes. J Surg Res 62: 233–242
Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM 2001 Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98: 2396–2402
Nöth U, Tuli R, Osyczka AM, Danielson KG, Tuan RS 2002 In vitro engineered cartilage constructs produced by press-coating biodegradable polymer with human mesenchymal stem cells. Tissue Eng 8: 131–144
Wada MR, Inagawa-Ogashiwa M, Shimizu S, Yasumoto S, Hashimoto N 2002 Generation of different fates from multipotent muscle stem cells. Development 129: 2987–2995
Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD 2001 Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 3: 778–784
Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV 1966 Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16: 381–390
Grigoriadis AE, Heersche JN, Aubin JE 1988 Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J Cell Biol 106: 2139–2151
Haynesworth SE, Goshima J, Goldberg VM, Caplan AI 1992 Characterization of cells with osteogenic potential from human marrow. Bone 13: 81–88
Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP 1997 Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64: 295–312
Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU 1998 In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238: 265–272
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR 1999 Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147
Wakitani S, Saito T, Caplan AI 1995 Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18: 1417–1426
George J, Kuboki Y, Miyata T 2006 Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds. Biotechnol Bioeng 95: 404–411
Holtorf HL, Datta N, Jansen JA, Mikos AG 2005 Scaffold mesh size affects the osteoblastic differentiation of seeded marrow stromal cells cultured in a flow perfusion bioreactor. J Biomed Mater Res A 74: 171–180
Okamoto M, Dohi Y, Ohgushi H, Shimaoka H, Ikeuchi M, Matsushima A, Yonemasu K, Hosoi H 2006 Influence of the porosity of hydroxyapatite ceramics on in vitro and in vivo bone formation by cultured rat bone marrow stromal cells. J Mater Sci Mater Med 17: 327–336
Oliveira JM, Rodrigues MT, Silva SS, Malafaya PB, Gomes ME, Viegas CA, Dias IR, Azevedo JT, Mano JF, Reis RL 2006 Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 27: 6123–6137
Shih YR, Chen CN, Tsai SW, Wang YJ, Lee OK 2006 Growth of mesenchymal stem cells on electrospun type I collagen nanofibers. Stem Cells 24: 2391–2397
Takahashi Y, Yamamoto M, Tabata Y 2005 Osteogenic differentiation of mesenchymal stem cells in biodegradable sponges composed of gelatin and beta-tricalcium phosphate. Biomaterials 26: 3587–3596
Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, Boyde A, Ruspantini I, Chistolini P, Rocca M, Giardino R, Cancedda R, Quarto R 2000 Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 49: 328–337
Bruder SP, Kraus KH, Goldberg VM, Kadiyala S 1998 The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 80: 985–996
Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, Smith A, Kadiyala S 2003 Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am 85-A: 1927–1935
Ohgushi H, Goldberg VM, Caplan AI 1989 Repair of bone defects with marrow cells and porous ceramic. Experiments in rats. Acta Orthop Scand 60: 334–339
Ge Z, Baguenard S, Lim LY, Wee A, Khor E 2004 Hydroxyapatite-chitin materials as potential tissue engineered bone substitutes. Biomaterials 25: 1049–1058
Jeong WK, Oh SH, Lee JH, Im GI 2008 Repair of osteochondral defect with a construct of mesenchymal stem cells and polydioxanone/polyvinyl alcohol scaffold. Biotechnol Appl Biochem 49: 155–164
Shao X, Goh JC, Hutmacher DW, Lee EH, Zigang G 2006 Repair of large articular osteochondral defects using hybrid scaffolds and bone marrow-derived mesenchymal stem cells in a rabbit model. Tissue Eng 12: 1539–1551
Meinel L, Fajardo R, Hofmann S, Langer R, Chen J, Snyder B, Vunjak-Novakovic G, Kaplan D 2005 Silk implants for the healing of critical size bone defects. Bone 37: 688–698
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH 2002 Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279–4295
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH 2001 Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7: 211–228
Rodbell M 1964 Metabolism of isolated fat cells. J Biol Chem 239: 375–380
Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF 1989 Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84: 1663–1670
Gimble JM, Katz AJ, Bunnell BA 2007 Adipose-derived stem cells for regenerative medicine. Circ Res 100: 1249–1260
Zheng B, Cao B, Li G, Huard J 2006 Mouse adipose-derived stem cells undergo multilineage differentiation in vitro but primarily osteogenic and chondrogenic differentiation in vivo. Tissue Eng 12: 1891–1901
Zhang X, Yang M, Lin L, Chen P, Ma KT, Zhou CY, Ao YF 2006 Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose–derived stem cells in vitro and in vivo. Calcif Tissue Int 79: 169–178
Yang M, Ma QJ, Dang GT, Ma K, Chen P, Zhou CY 2005 In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells expressing BMP-7. Cytotherapy 7: 273–281
Yang LY, Liu XM, Sun B, Hui GZ, Fei J, Guo LH 2004 Adipose tissue-derived stromal cells express neuronal phenotypes. Chin Med J (Engl) 117: 425–429
Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W 2003 Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum 48: 418–429
Timper K, Seboek D, Eberhardt M, Linscheid P, Christ-Crain M, Keller U, Muller B, Zulewski H 2006 Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun 341: 1135–1140
Tholpady SS, Katz AJ, Ogle RC 2003 Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro. Anat Rec A Discov Mol Cell Evol Biol 272: 398–402
Seo MJ, Suh SY, Bae YC, Jung JS 2005 Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328: 258–264
Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE 2004 Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp Neurol 187: 319–328
Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM, Rice HE 2002 Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 294: 371–379
Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Penicaud L, Casteilla L 2004 Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109: 656–663
Planat-Benard V, Menard C, Andre M, Puceat M, Perez A, Garcia-Verdugo JM, Penicaud L, Casteilla L 2004 Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94: 223–229
Ogawa R, Mizuno H, Hyakusoku H, Watanabe A, Migita M, Shimada T 2004 Chondrogenic and osteogenic differentiation of adipose-derived stem cells isolated from GFP transgenic mice. J Nippon Med Sch 71: 240–241
Morizono K, De Ugarte DA, Zhu M, Zuk P, Elbarbary A, Ashjian P, Benhaim P, Chen IS, Hedrick MH 2003 Multilineage cells from adipose tissue as gene delivery vehicles. Hum Gene Ther 14: 59–66
Mizuno H, Hyakusoku H 2003 Mesengenic potential and future clinical perspective of human processed lipoaspirate cells. J Nippon Med Sch 70: 300–306
Kokai LE, Rubin JP, Marra KG 2005 The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells. Plast Reconstr Surg 116: 1453–1460
Kang SK, Putnam LA, Ylostalo J, Popescu IR, Dufour J, Belousov A, Bunnell BA 2004 Neurogenesis of Rhesus adipose stromal cells. J Cell Sci 117: 4289–4299
Huang JI, Zuk PA, Jones NF, Zhu M, Lorenz HP, Hedrick MH, Benhaim P 2004 Chondrogenic potential of multipotential cells from human adipose tissue. Plast Reconstr Surg 113: 585–594
Guilak F, Lott KE, Awad HA, Cao Q, Hicok KC, Fermor B, Gimble JM 2006 Clonal analysis of the differentiation potential of human adipose-derived adult stem cells. J Cell Physiol 206: 229–237
Gimble JM, Guilak F 2003 Differentiation potential of adipose derived adult stem (ADAS) cells. Curr Top Dev Biol 58: 137–160
Fraser JK, Schreiber RE, Zuk PA, Hedrick MH 2004 Adult stem cell therapy for the heart. Int J Biochem Cell Biol 36: 658–666
Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte DA, Zhu M, Zuk PA, Lorenz HP, Benhaim P, Hedrick MH 2003 In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg 111: 1922–1931
Jack GS, Almeida FG, Zhang R, Alfonso ZC, Zuk PA, Rodriguez LV 2005 Processed lipoaspirate cells for tissue engineering of the lower urinary tract: implications for the treatment of stress urinary incontinence and bladder reconstruction. J Urol 174: 2041–2045
Mizuno H, Zuk PA, Zhu M, Lorenz HP, Benhaim P, Hedrick MH 2002 Myogenic differentiation of human processed lipoaspirate cells. Plast Reconstr Surg 109: 199–209
Nakagami H, Morishita R, Maeda K, Kikuchi Y, Ogihara T, Kaneda Y 2006 Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Thromb 13: 77–81
Schaffler A, Buchler C 2007 Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cells 25: 818–827
Casteilla L, Dani C 2006 Adipose tissue-derived cells: from physiology to regenerative medicine. Diabetes Metab 32: 393–401
Helder MN, Knippenberg M, Klein-Nulend J, Wuisman PI 2007 Stem cells from adipose tissue allow challenging new concepts for regenerative medicine. Tissue Eng 13: 1799–1808
Hicok KC, Du Laney TV, Zhou YS, Halvorsen YD, Hitt DC, Cooper LF, Gimble JM 2004 Human adipose-derived adult stem cells produce osteoid in vivo. Tissue Eng 10: 371–380
Lee JA, Parrett BM, Conejero JA, Laser J, Chen J, Kogon AJ, Nanda D, Grant RT, Breitbart AS 2003 Biological alchemy: engineering bone and fat from fat-derived stem cells. Ann Plast Surg 50: 610–617
Dragoo JL, Choi JY, Lieberman JR, Huang J, Zuk PA, Zhang J, Hedrick MH, Benhaim P 2003 Bone induction by BMP-2 transduced stem cells derived from human fat. J Orthop Res 21: 622–629
Dragoo JL, Lieberman JR, Lee RS, Deugarte DA, Lee Y, Zuk PA, Hedrick MH, Benhaim P 2005 Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat. Plast Reconstr Surg 115: 1665–1673
Hattori H, Masuoka K, Sato M, Ishihara M, Asazuma T, Takase B, Kikuchi M, Nemoto K, Ishihara M 2005 Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold. J Biomed Mater Res B Appl Biomater 76: 230–239
Peterson B, Zhang J, Iglesias R, Kabo M, Hedrick M, Benhaim P, Lieberman JR 2005 Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tissue Eng 11: 120–129
Chang SC, Chuang H, Chen YR, Yang LC, Chen JK, Mardini S, Chung HY, Lu YL, Ma WC, Lou J 2004 Cranial repair using BMP-2 gene engineered bone marrow stromal cells. J Surg Res 119: 85–91
Lieberman JR, Daluiski A, Stevenson S, Wu L, McAllister P, Lee YP, Kabo JM, Finerman GA, Berk AJ, Witte ON 1999 The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. J Bone Joint Surg Am 81: 905–917
Tsuda H, Wada T, Yamashita T, Hamada H 2005 Enhanced osteoinduction by mesenchymal stem cells transfected with a fiber-mutant adenoviral BMP2 gene. J Gene Med 7: 1322–1334
De Kok IJ, Peter SJ, Archambault M, van den Bos C, Kadiyala S, Aukhil I, Cooper LF 2003 Investigation of allogeneic mesenchymal stem cell-based alveolar bone formation: preliminary findings. Clin Oral Implants Res 14: 481–489
Mankani MH, Kuznetsov SA, Wolfe RM, Marshall GW, Robey PG 2006 In vivo bone formation by human bone marrow stromal cells: reconstruction of the mouse calvarium and mandible. Stem Cells 24: 2140–2149
Krebsbach PH, Mankani MH, Satomura K, Kuznetsov SA, Robey PG 1998 Repair of craniotomy defects using bone marrow stromal cells. Transplantation 66: 1272–1278
Bidic SM, Calvert JW, Marra K, Kumta P, Campbell P, Mitchell R, Wigginton W, Hollinger JO, Weiss L, Mooney MP 2003 Rabbit calvarial wound healing by means of seeded Caprotite scaffolds. J Dent Res 82: 131–135
Radice M, Brun P, Cortivo R, Scapinelli R, Battaliard C, Abatangelo G 2000 Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res 50: 101–109
Weng Y, Wang M, Liu W, Hu X, Chai G, Yan Q, Zhu L, Cui L, Cao Y 2006 Repair of experimental alveolar bone defects by tissue-engineered bone. Tissue Eng 12: 1503–1513
Shang Q, Wang Z, Liu W, Shi Y, Cui L, Cao Y 2001 Tissue-engineered bone repair of sheep cranial defects with autologous bone marrow stromal cells. J Craniofac Surg 12: 586–593
Kraut RA 1987 The use of allogeneic bone for alveolar cleft grafting. Oral Surg Oral Med Oral Pathol 64: 278–282
Hibi H, Yamada Y, Ueda M, Endo Y 2006 Alveolar cleft osteoplasty using tissue-engineered osteogenic material. Int J Oral Maxillofac Surg 35: 551–555
Kadiyala S, Young RG, Thiede MA, Bruder SP 1997 Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 6: 125–134
Baumann A, Ewers R 2000 Application of the buccal fat pad in oral reconstruction. J Oral Maxillofac Surg 58: 389–392; discussion 392–393.
Hudson JW, Anderson JG, Russell RM Jr, Anderson N, Chambers K 1995 Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80: 24–27
Dudas JR, Marra KG, Cooper GM, Penascino VM, Mooney MP, Jiang S, Rubin JP, Losee JE 2006 The osteogenic potential of adipose-derived stem cells for the repair of rabbit calvarial defects. Ann Plast Surg 56: 543–548
Yoon E, Dhar S, Chun DE, Gharibjanian NA, Evans GR 2007 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 13: 619–627
Mauney JR, Nguyen T, Gillen K, Kirker-Head C, Gimble JM, Kaplan DL 2007 Engineering adipose-like tissue in vitro and in vivo utilizing human bone marrow and adipose-derived mesenchymal stem cells with silk fibroin 3D scaffolds. Biomaterials 28: 5280–5290
Cui L, Liu B, Liu G, Zhang W, Cen L, Sun J, Yin S, Liu W, Cao Y 2007 Repair of cranial bone defects with adipose derived stem cells and coral scaffold in a canine model. Biomaterials 28: 5477–5486
Follmar KE, Prichard HL, DeCroos FC, Wang HT, Levin LS, Klitzman B, Olbrich KC, Erdmann D 2007 Combined bone allograft and adipose-derived stem cell autograft in a rabbit model. Ann Plast Surg 58: 561–565
Erfani S, Maldonado TS, Crisera CA, Warren SM, Lee S, Longaker MT 2001 An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting. Plast Reconstr Surg 108: 403–410
Resel E, Martinez-Sanz E, Gonzalez I, Trinidad E, Garcillan B, Amoros M, Alonso-Banuelos C, Gonzalez-Meli B, Lagaron E, Murillo J, Del Rio A, Barrio C, Lopez M, Martinez-Alvarez C 2007 In vitro manipulation of cleft palate connective tissue: setting the bases of a proposed new treatment. J Surg Res 138: 111–120
Carstanjen B, Desbois C, Hekmati M, Behr L 2006 Successful engraftment of cultured autologous mesenchymal stem cells in a surgically repaired soft palate defect in an adult horse. Can J Vet Res 70: 143–147
Akita S, Fukui M, Nakagawa H, Fujii T, Akino K 2004 Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor. Wound Repair Regen 12: 252–259
Noel D, Gazit D, Bouquet C, Apparailly F, Bony C, Plence P, Millet V, Turgeman G, Perricaudet M, Sany J, Jorgensen C 2004 Short-term BMP-2 expression is sufficient for in vivo osteochondral differentiation of mesenchymal stem cells. Stem Cells 22: 74–85
Tang TT, Xu XL, Dai KR, Yu CF, Yue B, Lou JR 2005 Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice. Chin J Traumatol 8: 3–7
Zachos TA, Shields KM, Bertone AL 2006 Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6. J Orthop Res 24: 1279–1291
Diefenderfer DL, Osyczka AM, Reilly GC, Leboy PS 2003 BMP responsiveness in human mesenchymal stem cells. Connect Tissue Res 44: 305–311
Osyczka AM, Diefenderfer DL, Bhargave G, Leboy PS 2004 Different effects of BMP-2 on marrow stromal cells from human and rat bone. Cells Tissues Organs 176: 109–119
Einhorn TA 2003 Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am 85-A: 82–88
Fujibayashi S, Neo M, Kim HM, Kokubo T, Nakamura T 2003 A comparative study between in vivo bone ingrowth and in vitro apatite formation on Na2O-CaO-SiO2 glasses. Biomaterials 24: 1349–1356
Kokubo T, Ito S, Huang ZT, Hayashi T, Sakka S, Kitsugi T, Yamamuro T 1990 Ca, P-rich layer formed on high-strength bioactive glass-ceramic A-W. J Biomed Mater Res 24: 331–343
Kokubo T, Hanakawa M, Kawashita M, Minoda M, Beppu T, Miyamoto T, Nakamura T 2004 Apatite formation on non-woven fabric of carboxymethylated chitin in SBF. Biomaterials 25: 4485–4488
Chou YF, Chiou WA, Xu Y, Dunn JC, Wu BM 2004 The effect of pH on the structural evolution of accelerated biomimetic apatite. Biomaterials 25: 5323–5331
Chou YF, Huang W, Dunn JC, Miller TA, Wu BM 2005 The effect of biomimetic apatite structure on osteoblast viability, proliferation, and gene expression. Biomaterials 26: 285–295
Chou YF, Dunn JC, Wu BM 2005 In vitro response of MC3T3–E1 pre-osteoblasts within three-dimensional apatite-coated PLGA scaffolds. J Biomed Mater Res B Appl Biomater 75: 81–90
Cowan CM, Shi YY, Aalami OO, Chou YF, Mari C, Thomas R, Quarto N, Contag CH, Wu B, Longaker MT 2004 Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol 22: 560–567
Gori F, Thomas T, Hicok KC, Spelsberg TC, Riggs BL 1999 Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res 14: 1522–1535
Lou J, Tu Y, Li S, Manske PR 2000 Involvement of ERK in BMP-2 induced osteoblastic differentiation of mesenchymal progenitor cell line C3H10T1/2. Biochem Biophys Res Commun 268: 757–762
Noth U, Tuli R, Seghatoleslami R, Howard M, Shah A, Hall DJ, Hickok NJ, Tuan RS 2003 Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res 291: 201–211
Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF 2000 Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 275: 9645–9652
Bost F, Aouadi M, Caron L, Even P, Belmonte N, Prot M, Dani C, Hofman P, Pages G, Pouyssegur J, Le Marchand-Brustel Y, Binetruy B 2005 The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis. Diabetes 54: 402–411
Jeon ES, Kang YJ, Song HY, Woo JS, Jung JS, Kim YK, Kim JH 2005 Role of MEK-ERK pathway in sphingosylphosphorylcholine-induced cell death in human adipose tissue-derived mesenchymal stem cells. Biochim Biophys Acta 1734: 25–33
Kang YJ, Jeon ES, Song HY, Woo JS, Jung JS, Kim YK, Kim JH 2005 Role of c-Jun N-terminal kinase in the PDGF-induced proliferation and migration of human adipose tissue-derived mesenchymal stem cells. J Cell Biochem 95: 1135–1145
Edwards PC, Ruggiero S, Fantasia J, Burakoff R, Moorji SM, Paric E, Razzano P, Grande DA, Mason JM 2005 Sonic hedgehog gene-enhanced tissue engineering for bone regeneration. Gene Ther 12: 75–86
Parr BA, McMahon AP 1994 Wnt genes and vertebrate development. Curr Opin Genet Dev 4: 523–528
Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML 2001 LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107: 513–523
Boland GM, Perkins G, Hall DJ, Tuan RS 2004 Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 93: 1210–1230
Chang J, Sonoyama W, Wang Z, Jin Q, Zhang C, Krebsbach PH, Giannobile W, Shi S, Wang CY 2007 Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J Biol Chem 282: 30938–30948
Singh S, Yin X, Pisano MM, Greene RM 2007 Molecular profiles of mitogen activated protein kinase signaling pathways in orofacial development. Birth Defects Res A Clin Mol Teratol 79: 35–44
Kundu AK, Putnam AJ 2006 Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells. Biochem Biophys Res Commun 347: 347–357
Globus RK, Moursi A, Zimmerman D, Lull J, Damsky C 1995 Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation. ASGSB Bull 8: 19–28
Xiao G, Wang D, Benson MD, Karsenty G, Franceschi RT 1998 Role of the alpha2-integrin in osteoblast-specific gene expression and activation of the Osf2 transcription factor. J Biol Chem 273: 32988–32994
Chen Q, Kinch MS, Lin TH, Burridge K, Juliano RL 1994 Integrin-mediated cell adhesion activates mitogen-activated protein kinases. J Biol Chem 269: 26602–26605
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Zuk, P. Tissue Engineering Craniofacial Defects With Adult Stem Cells? Are We Ready Yet?. Pediatr Res 63, 478–486 (2008). https://doi.org/10.1203/PDR.0b013e31816bdf36
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DOI: https://doi.org/10.1203/PDR.0b013e31816bdf36
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