Adipose-derived adult stromal cells heal critical-size mouse calvarial defects

In adults and children over two years of age, large cranial defects do not reossify successfully, posing a substantial biomedical burden. The osteogenic potential of bone marrow stromal (BMS) cells has been documented. This study investigates the in vivo osteogenic capability of adipose-derived adult stromal (ADAS) cells, BMS cells, calvarial-derived osteoblasts and dura mater cells to heal critical-size mouse calvarial defects. Implanted, apatite-coated, PLGA scaffolds seeded with ADAS or BMS cells produced significant intramembranous bone formation by 2 weeks and areas of complete bony bridging by 12 weeks as shown by X-ray analysis, histology and live micromolecular imaging. The contribution of implanted cells to new bone formation was 84–99% by chromosomal detection. These data show that ADAS cells heal critical-size skeletal defects without genetic manipulation or the addition of exogenous growth factors.

[1]  M. Longaker,et al.  Basic fibroblast growth factor and transforming growth factor beta-1 expression in the developing dura mater correlates with calvarial bone formation. , 1999, Plastic and reconstructive surgery.

[2]  Min Zhu,et al.  Human adipose tissue is a source of multipotent stem cells. , 2002, Molecular biology of the cell.

[3]  M. Longaker,et al.  Age-related changes in the biomolecular mechanisms of calvarial osteoblast biology affect fibroblast growth factor-2 signaling and osteogenesis.Vol. 278 (2003) 32005–32013 , 2003 .

[4]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[5]  Stem cells: Fusion brings down barriers , 2003, Nature.

[6]  G. Im,et al.  Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. , 2001, The Journal of bone and joint surgery. British volume.

[7]  J Marler,et al.  Transplantation of cells in matrices for tissue regeneration. , 1998, Advanced drug delivery reviews.

[8]  G. Vassilopoulos,et al.  Transplanted bone marrow regenerates liver by cell fusion , 2003, Nature.

[9]  D. Mooney,et al.  Engineered bone development from a pre-osteoblast cell line on three-dimensional scaffolds. , 2000, Tissue engineering.

[10]  J Gordon McComb,et al.  Correction of Large (>25 cm2) Cranial Defects with “Reinforced” Hydroxyapatite Cement: Technique and Complications , 2003, Neurosurgery.

[11]  Y. Bando,et al.  A comparative study of ultrastructures of the interfaces between four kinds of surface-active ceramic and bone. , 1992, Journal of biomedical materials research.

[12]  Farshid Guilak,et al.  Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. , 2002, Biochemical and biophysical research communications.

[13]  J G McCarthy,et al.  Studies in cranial suture biology: in vitro cranial suture fusion. , 1996, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[14]  J. Triffitt,et al.  Human bone tissue formation in diffusion chamber culture in vivo by bone-derived cells and marrow stromal fibroblastic cells. , 1995, Bone.

[15]  Prosper Benhaim,et al.  Bone induction by BMP‐2 transduced stem cells derived from human fat , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[16]  A I Caplan,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. , 1998, Experimental cell research.

[17]  J. Laser,et al.  Biological Alchemy: Engineering Bone and Fat From Fat-Derived Stem Cells , 2003, Annals of plastic surgery.

[18]  Johnny Huard,et al.  Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. , 2002, The Journal of clinical investigation.

[19]  M. Grompe,et al.  Cell fusion is the principal source of bone-marrow-derived hepatocytes , 2003, Nature.

[20]  S. Stupp,et al.  Nanoapatite and organoapatite implants in bone: histology and ultrastructure of the interface. , 1995, Journal of biomedical materials research.

[21]  M. Hedrick,et al.  Myogenic Differentiation by Human Processed Lipoaspirate Cells , 2002, Plastic and reconstructive surgery.

[22]  J. Le Huec,et al.  Influence of porosity on the mechanical resistance of hydroxyapatite ceramics under compressive stress. , 1995, Biomaterials.

[23]  W. Wilkison,et al.  Neurogenic differentiation of murine and human adipose-derived stromal cells. , 2002, Biochemical and biophysical research communications.

[24]  Ralph W. Passarelli,et al.  Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[26]  J M Polak,et al.  Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. , 2001, Tissue engineering.

[27]  S. Ahmed,et al.  Biology and clinical applications , 2004 .

[28]  W. Wilkison,et al.  Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. , 2001, Tissue engineering.

[29]  W. Wilkison,et al.  Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis. , 2001, Metabolism: clinical and experimental.

[30]  Johnny Huard,et al.  BMP4-expressing muscle-derived stem cells differentiate into osteogenic lineage and improve bone healing in immunocompetent mice. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[31]  A. Caplan,et al.  Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5‐azacytidine , 1995, Muscle & nerve.

[32]  J. Glowacki,et al.  Induced Osteogenesis for Repair and Construction in the Craniofacial Region , 1980, Plastic and reconstructive surgery.

[33]  D. Rowe,et al.  Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. , 1997, Transplantation.

[34]  K. Xia,et al.  In vitro chondrogenesis of human bone marrow-derived mesenchymal progenitor cells in monolayer culture: activation by transfection with TGF-beta2. , 2003, Tissue & cell.

[35]  A I Caplan,et al.  Characterization of cells with osteogenic potential from human marrow. , 1992, Bone.

[36]  M. Longaker,et al.  Regional Differentiation of Cranial Suture‐Associated Dura Mater In Vivo and In Vitro: Implications for Suture Fusion and Patency , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  L. Bonewald,et al.  Effects of transforming growth factor β on bone nodule formation and expression of bone morphogenetic protein 2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long‐term cultures of fetal rat calvarial osteoblasts , 1994 .

[38]  U. Hübner,et al.  How to optimize seeding and culturing of human osteoblast-like cells on various biomaterials. , 2002, Biomaterials.

[39]  M. Longaker,et al.  New Strategies for Craniofacial Repair and Replacement: A Brief Review , 2003, The Journal of craniofacial surgery.

[40]  P. Hatton,et al.  Surface topography of hydroxyapatite affects ROS17/2.8 cells response. , 2002, Pesquisa odontologica brasileira = Brazilian oral research.

[41]  Bioceramics , 2022, An Introduction to Biomaterials Science and Engineering.

[42]  F. Guilak,et al.  Multipotent Stromal Cells Derived From the Infrapatellar Fat Pad of the Knee , 2003, Clinical orthopaedics and related research.

[43]  K. Satomura,et al.  Repair of craniotomy defects using bone marrow stromal cells. , 1998, Transplantation.

[44]  J. J. Grote,et al.  The biocompatibility of hydroxyapatite ceramic: a study of retrieved human middle ear implants. , 1990, Journal of biomedical materials research.

[45]  A. Katz,et al.  Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[46]  H. Lorenz,et al.  In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. , 2003, Plastic and reconstructive surgery.

[47]  S. Both,et al.  Bone tissue-engineered implants using human bone marrow stromal cells: effect of culture conditions and donor age. , 2002, Tissue engineering.

[48]  B. Sarkar.  Fatigue of brittle materials—A critical appraisal , 1995 .

[49]  E. J. Frazza,et al.  A new absorbable suture. , 1971, Journal of biomedical materials research.

[50]  Anne Elixhauser,et al.  The healthcare cost and utilization project: an overview. , 2002, Effective clinical practice : ECP.

[51]  N Passuti,et al.  Osteogenic potential in vitro of human bone marrow cells cultured on macroporous biphasic calcium phosphate ceramic. , 1999, Journal of biomedical materials research.

[52]  M. Yoshinari,et al.  Substrate affects the initial attachment and subsequent behavior of human osteoblastic cells (Saos-2). , 2001, Biomaterials.

[53]  T. Uemura,et al.  In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of transplanted bone marrow-derived osteoblastic cells. , 2001, Journal of biomedical materials research.

[54]  J. McCarthy,et al.  Studies in Cranial Suture Biology: Regional Dura Mater Determines in Vitro Cranial Suture Fusion , 1997, Plastic and reconstructive surgery.

[55]  G. Daculsi,et al.  Calcium-deficient apatite: a first in vivo study concerning bone ingrowth. , 2003, Journal of biomedical materials research. Part A.

[56]  Feng Zhao,et al.  [Tissue engineering study on chitosan-gelatin/hydroxyapatite composite scaffolds--osteoblasts culture]. , 2002, Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery.

[57]  Freddie H. Fu,et al.  Effect of Bone Morphogenetic Protein-2-Expressing Muscle-Derived Cells on Healing of Critical-Sized Bone Defects in Mice , 2001, The Journal of bone and joint surgery. American volume.

[58]  Jay R Lieberman,et al.  The role of growth factors in the repair of bone. Biology and clinical applications. , 2002, The Journal of bone and joint surgery. American volume.

[59]  Stephen M Warren,et al.  Age-related Changes in the Biomolecular Mechanisms of Clvarial Osteoblast Biology Affect Fibroblast Growth Factor-2 Signaling and Osteogenesis* , 2003, Journal of Biological Chemistry.