Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

Authors

    Sabrina Ena, Julia Ino, Aurelie Neirinck, Sandra Pietri, Anna Tury, Enrico Bastianelli

DOI:

https://doi.org/10.18063/jmds.v1i2.135

Keywords:

adipose tissue-derived mesenchymal stromal cells, bone marrow-derived mesenchymal stromal cells, MSC, proliferation, yield, immunophenotype, osteogenic differentiation, in vivo, preclinical, regenerative medicine, cell therapy, human, review

Abstract

Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo.

References

Friedenstein A J, Petrakova K V, Kurolesova A I, et al. 1968, Heterotopic of bone marrow. Analysis of precur-sor cells for osteogenic and hematopoietic tissues. Transplantation, vol.6(2): 230–247, http://dx.doi.org/10.1097/00007890-196803000-00009

Friedenstein A J, Chailakhjan R K and Lalykina K S, 1970, The development of fibroblast colonies in mon-olayer cultures of guinea-pig bone marrow and spleen cells. Cell Proliferation, vol.3(4): 393–403, http://dx.doi.org/10.1111/j.1365-2184.1970.tb00347.x.

Ashton B A, Allen T D, Howlett C R, et al. 1980, For-mation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clinical Orthopaedics and Related Research, vol.151: 294–307, http://dx.doi.org/10.1097/00003086-198009000-00040

Bab I, Ashton B A, Gazit D, et al. 1986, Kinetics and differentiation of marrow stromal cells in diffusion cha-mbers in vivo. Journal of Cell Science, vol.84: 139–151.

Owen M, 1988, Marrow stromal stem cells. Journal of Cell Science, Vol.10(Suppl): 63–76. http://dx.doi.org/10.1242/jcs.1988.Supplement_10.5

Pittenger M F, Mackay A M, Beck S C, et al. 1999, Multilineage potential of adult human mesenchymal stem cells. Science, vol.284(5411): 143–147. http://dx.doi.org/10.1126/science.284.5411.143

Zuk P A, Zhu M, Ashjian P, et al. 2002, Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, vol.13(12): 4279–4295. http://dx.doi.org/10.1091/mbc.E02-02-0105

Dezawa M, Ishikawa H, Itokazu Y, et al. 2005, Bone Marrow Stromal Cells Generate Muscle Cells and Repair Muscle Degeneration. Science, vol.309(5732): 314–317, http://dx.doi.org/10.1126/science.1110364

Gang E J, Jeong J A, Hong S H, et al. 2004, Myogenic Differentiation of Mesenchymal Stem Cells Isolated from Human Umbilical Cord Blood. Cell Stem Cell, vol.22(4): 617–624, http://dx.doi.org/10.1634/stemcells.22-4-617

De Bari C, Dell’Accio F, Tylzanowski P, et al. 2001, Multipotent mesenchymal stem cells from adult synovi-al membrane. Arthritis Rheumatology, vol.44(8): 1928– 1942. http://dx.doi.org/10.1002/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P

De Bari C, Dell’Accio F, Vandenabeele F, et al. 2003, Skeletal muscle repair by adult mesenchymal stem cells from synovial membrane. The Journal of Cell Biology, vol.160(6): 909–918. http://dx.doi.org/10.1083/jcb.200212064

Zuk P, Zhu M, Mizuno H, et al. 2001, Multilineage Cells from Human Adipose Tissue: Implications for Cell- Based Therapies. Tissue Engineering, vol.7(2): 211–228. http://dx.doi.org/10.1089/107632701300062859

Parolini O, Alviano F, Bagnara G P, et al. 2008, Concise review: isolation and characterization of cells from hu-man term placenta: outcome of the first international workshop on placenta derived stem cells. Stem Cells, vol.26(2): 300–311. http://dx.doi.org/10.1634/stemcells.2007-0594

Erices A, Conget P and Minguell J J, 2000, Mesen-chymal progenitor cells in human umbilical cord blood. British Journal of Haematology, vol.109(1): 235–242. http://dx.doi.org/10.1046/j.1365-2141.2000.01986.x

Zvaifler N J, Marinova-Mutafchieva L, Adams G, et al. 2000, Mesenchymal precursor cells in the blood of normal individuals, Arthritis Research, vol.2: 477–488. http://dx.doi.org/10.1186/ar130

Miura M, Gronthos S and Zhao M 2003, Stem cells from human exfoliated deciduous teeth. Proceeding of the National Academy of Sciences of the United States of America, vol.100(10): 5807–5812. http://dx.doi.org/10.1073/pnas.0937635100

Toma J, McKenzie I, Bagli D, et al. 2005, Isolation and characterization of multipotent skin-derived precursors from human skin. Stem Cells, vol.23(6): 727–737. http://dx.doi.org/10.1634/stemcells.2004-0134

Song L, Young N J and Webb N E, 2005, Origin and characterization of multipotential mesenchymal stem cells derived from adult trabecular bone. Stem Cells Development, vol.14(6): 712–721, http://dx.doi.org/10.1089/scd.2005.14.712

Dominici M, Le blanc K, Mueller I, et al. 2006, Minim-al criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy po-sition statement. Cytotherapy, vol.8(4): 315–317. http://dx.doi.org/10.1080/14653240600855905

Lazarus H, Haynesworth S, Gerson S, et al., 1995, Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplantation, vol.16(4): 557–564.

ClinicalTrials.gov: A service of the U.S. National Insti-tutes of Health, n.d., viewed on November 8, 2015,

Tseng S S, Lee M A and Reddi A H, 2008, Nonunions and the potential of stem cells in fracture-healing. The Journal of Bone and Joint Surgery, vol.90 (Suppl 1): 92–98. http://dx.doi.org/10.2106/JBJS.G.01192

Gómez-Barrena E, Rosset P, Lozano D, et al. 2015, Bone fracture healing: Cell therapy in delayed unions and nonunions. Bone, vol.70: 93–101. http://dx.doi.org/10.1016/j.bone.2014.07.033

Pieske O, Wittmann A, Zaspel J, et al. 2009, Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones. Journal of Trauma Management & Outcomes, vol.3: 11. http://dx.doi.org/10.1186/1752-2897-3-11

Sen M K and Miclau T, 2007, Autologous iliac crest bone graft: Should it still be the gold standard for treat-ing nonunions? Injury, vol.38(1): S75–S80. http://dx.doi.org/10.1016/j.injury.2007.02.012

Hernigou P and Beaujean F, 1997, Abnormalities in the bone marrow of the iliac crest in patients Who Have os-teonecrosis secondary to corticosteroid therapy or alco-hol abuse. The Journal of Bone & Joint Surgery, vol.79(7): 1047–1053.

Hauzeur J P and Gangji V, 2010, Phases 1-3 clinical tri-als using adult stem cells in osteonecrosis and nonunion fractures. Stem Cells International, vol.2010: 410170. http://dx.doi.org/10.4061/2010/410170

Mathieu M, Rigutto S, Ingels A, et al. 2013, Decreased pool of mesenchymal stem cells is associated with al-tered chemokines serum levels in atrophic nonunion fractures. Bone, vol.53(2): 391–398. http://dx.doi.org/10.1016/j.bone.2013.01.005

Mendicino M, Bailey A M, Wonnacott K, et al. 2014, MSC-based product characterization for clinical trials: An FDA perspective. Cell Stem Cell, vol.14(2):141–145. http://dx.doi.org/10.1016/j.stem.2014.01.013

Roemeling-van Rhijn M, Khairoun M, Korevaar S S, et al. 2013, Human bone marrow- and adipose tissue-derived mesenchymal stromal cells are immunosuppressive in vitro and in a humanized allograft rejection model. Journal of Stem Cell Research & Therapy, Suppl 6(1): 20780. http://dx.doi.org/10.4172/2157-7633.S6-001

Strioga M, Viswanathan S, Darinskas A, et al. 2012, Same or not the same? Comparison of adipose tissue- derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells and Development, vol.21(14): 2724–2752.

http://dx.doi.org/10.1089/scd.2011.0722

Bourin P, Bunnell B A, Casteilla L, et al. 2013, Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy, vol.15(6): 641–648. http://dx.doi.org/10.1016/j.jcyt.2013.02.006

Bochev I, Elmadjian G, Kyurkchiev D, et al. 2008, Me-senchymal stem cells from human bone marrow or adi-pose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro. Cell Biology International, vol.32(4): 384–393. http://dx.doi.org/10.1016/j.cellbi.2007.12.007

De Ugarte D A, Morizono K, Elbarbary A, et al. 2003, Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs, vol.174: 101–109. http://dx.doi.org/10.1159/000071150.

De Ugarte D A, Alfonso Z, Zuk P A, et al. 2003, Diffe-rential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunology Letters, vol.89(2–3): 267–270. http://dx.doi.org/10.1016/S0165-2478(03)00108-1

Sakaguchi Y, Sekiya I, Yagishita Y, et al. 2005, Com-parison of Human Stem Cells Derived From Various Mesenchymal Tissues. Arthritis & Rheumatism, vol.52(8): 2521–2529. http://dx.doi.org/10.1002/art.21212

Chen H T, Lee M J, Chen C H, et al. 2012, Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. Journal of Cellular and Molecular Medicine, vol.16(3): 582–592. http://dx.doi.org/10.1111/j.1582-4934.2011.01335.x

Dmitrieva R I, Minullina I R, Bilibina A A, et al. 2012, Bone marrow- and subcutaneous adipose tissue-derived mesenchymal stem cells: differences and similarities. Cell Cycle, vol.11(2): 377–383. http://dx.doi.org/10.4161/cc.11.2.18858

Pachón-Peña G, Yu G, Tucker A, et al. 2011, Stromal stem cells from adipose tissue and bone marrow of age-matched female donors display distinct immuno-phenotypic profiles. Journal of Cellular Physiology, vol.226(3): 843–851. http://dx.doi.org/10.1002/jcp.22408

Amable P R, Teixeira M V, Carias R B, et al. 2014, Protein synthesis and secretion in human mesenchymal cells de-rived from bone marrow, adipose tissue and Wharton's jelly. Stem Cell Research & Therapy, vol.5(2): 53. http://dx.doi.org/10.1186/scrt442

Zhu X, Shi W, Tai W, et al. 2012, The comparition of biological characteristics and multilineage differentia-tion of bone marrow and adipose derived Mesenchymal stem cells. Cell Tissue Research, vol.350(2): 277–287. http://dx.doi.org/10.1007/s00441-012-1453-1

Brocher J, Janicki P, Voltz P, et al. 2013, Inferior ectopic bone formation of mesenchymal stromal cells from adi-pose tissue compared to bone-marrow: rescue by chon-drogenic pre-induction. Stem Cell Research, vol.11(3): 1393–1406. http://dx.doi.org/10.1016/j.scr.2013.07.008

Wagner W, Wein F, Seckinger A, et al. 2005, Compara-tive characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Experimental Hematology, vol.33(11): 1402–1416. http://dx.doi.org/10.1016/j.exphem.2005.07.003

Vishnubalaji R, Al-Nbaheen M, Kadalmani B, et al. 2012, Comparative investigation of the differentiation capability of bone-marrow and adipose-derived mesen-chymal stem cells by qualitative and quantitative analy-sis. Cell &Tissue Research, vol.347(2): 419–427. http://dx.doi.org/10.1007/s00441-011-1306-3

Im G I, Shin Y W and Lee K B, 2005, Do adipose tis-sue-derived mesenchymal stem cells have the same os-teogenic and chondrogenic potential as bone marrow- derived cells? Osteoarthritis Cartilage, vol.13(10): 845– 853. http://dx.doi.org/10.1016/j.joca.2005.05.005

Jin H J, Bae Y K, Kim M, et al. 2013, Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. International Journal of Mole-cular Sciences, vol.14(9): 17986–18001. http://dx.doi.org/10.3390/ijms140917986

Reinisch A, Etchart N, Thomas D, et al. 2015, Epige-netic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hemato-poietic niche formation. Blood, vol.125(2): 249–260. http://dx.doi.org/10.1182/blood-2014-04-572255

Najar M, Raicevic G, Boufker H I, et al. 2010, Mesen-chymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton's Jelly and bone marrow sources. Cellular Immunology, vol.264(2): 171– 179. http://dx.doi.org/10.1016/j.cellimm.2010.06.006

Niemeyer P, Kornacker M, Mehlhorn A, et al. 2007, Comparison of immunological properties of bone mar-row stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro. Tissue Engineering, vol.13(1):111–121. http://dx.doi.org/10.1089/ten.2006.0114

Zhang Z Y, Teoh S H, Chong M S, et al. 2009, Superior osteogenic capacity for bone tissue engineering of fetal compared with perinatal and adult mesenchymal stem cells. Stem Cells, vol.27(1): 126–137. http://dx.doi.org/10.1634/stemcells.2008-0456

Jo C H, Yoon P W, Kim H, et al. 2013, Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model. Cell Tissue Research, vol.353(1): 41–52. http://dx.doi.org/10.1007/s00441-013-1619-5

Hattori H, Masuoka K, Sato M, et al. 2006, Bone for-mation using human adipose tissue-derived stromal cells and a biodegradable scaffold. Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol.76B(1):230–239. http://dx.doi.org/10.1002/jbm.b.30357

Wen Y, Jiang B, Cui J, et al. 2013, Superior osteogenic capacity of different mesenchymal stem cells for bone tissue engineering. Oral Surgery Oral Medicine Oral Pathology Oral Radiology, vol.116(5): e324–e332. http://dx.doi.org/10.1016/j.oooo.2012.02.024

Hayashi O, Katsube Y, Hirose M, et al. 2008, Compari-son of osteogenic ability of rat mesenchymal stem cells from bone marrow, periosteum, and adipose tissue. Cal-cified Tissue International, vol.82: 238–247. http://dx.doi.org/10.1007/s00223-008-9112-y

Lin L, Shen Q, Wei X, et al. 2009, Comparison of os-teogenic potentials of BMP4 transduced stem cells from autologous bone marrow and fat tissue in a rabbit model of calvarial defects. Calcified Tissue International, vol.85(1): 55–65. http://dx.doi.org/10.1007/s00223-009-9250-x

Kang B J, Ryu H H, Park S S, et al. 2012, Comparing the osteogenic potential of canine mesenchymal stem cells derived from adipose tissues, bone marrow, umbil-ical cord blood, and Wharton’s jelly for treating bone defects. Journal of Veterinary Science, vol.13(3): 299–310. http://dx.doi.org/10.4142/jvs.2012.13.3.299

Stockmann P, Park J, von Wilmowsky C, et al. 2012, Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells a comparison of different tissue sources. Journal of Cra-nio-maxillo-facial Surgery, vol.40(4): 310–320. http://dx.doi.org/10.1016/j.jcms.2011.05.004

Niemeyer P, Fechner K, Milz S, et al. 2010. Comparison of mesenchymal stem cells from bone marrow and adi-pose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials, vol.31(13): 3572–3579 http://dx.doi.org/10.1016/j.biomaterials.2010.01.085

Abdallah B M and Kassem M 2008, Human mesen-chymal stem cells: From basic biology to clinical applications. Gene Therapy, vol.15(2): 109–116. http://dx.doi.org/10.1038/sj.gt.3303067

Ullah I, Subbarao R B and Rho G J, 2015, Human me-senchymal stem cells - current trends and future pros-pective. Bioscience Reports, vol.35(2) pii: e00191. http://dx.doi.org/10.1042/BSR20150025

Kern S, Eichler H, Stoeve J, et al. 2006, Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, vol.24(5): 1294–1301. http://dx.doi.org/10.1634/stemcells.2005-0342

Mosna F, Sensebé L and Krampera M 2010, Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide. Stem Cells Development, vol.19(10): 1449–1470. http://dx.doi.org/10.1089/scd.2010.0140

Hass R, Kasper C, Böhm S, et al. 2011, Different popu-lations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-der-ived MSC. Cell Communication & Signaling, vol.9: 12. http://dx.doi.org/10.1186/1478-811X-9-12

Li J, Wong W H, Chan S, et al. 2011, Factors affecting mesenchymal stromal cells yield from bone marrow aspiration. Chinese Journal of Cancer Research, vol.23(1): 43–48. http://dx.doi.org/10.1007/s11670-011-0043-1

Fekete N, Rojewski MT, Fürst D, et al. 2012, GMP- compliant isolation and large-scale expansion of bone marrow-derived MSC. PLoS One, vol.7(8): e43255. http://dx.doi.org/10.1371/journal.pone.0043255

Ramakrishnan A, Torok-Storb B and Pillai M M, 2013, Primary marrow-derived stromal cells: isolation and manipulation. Methods in Molecular Biology, vol.1035: 75–101. http://dx.doi.org/10.1007/978-1-62703-508-8_8

Rada T, Reis R L and Gomes ME, 2009, Adipose tis-sue-derived stem cells and their application in bone and cartilage tissue engineering. Tissue Engineering Part B Reviews, vol.15(2): 113–125. http://dx.doi.org/10.1089/ten.teb.2008.0423

Gimble J M, Katz A J and Bunnell B A, 2007, Adi-pose-derived stem cells for regenerative medicine, Cir-culation Research, vol.100(9): 1249–1260. http://dx.doi.org/10.1161/01.RES.0000265074.83288.09

Locke M, Windsor J and Dunbar P R, 2009, Human adipose-derived stem cells: isolation, characterization and applications in surgery. ANZ Journal of Surgery, vol.79(4): 235–244. http://dx.doi.org/10.1111/j.1445-2197.2009.04852.x

Bunnell B A, Flaat M, Gagliardi C, et al. 2008, Adi-pose-derived stem cells: Isolation, expansion and diffe-rentiation. Methods, vol.45(2): 115–120.

http://dx.doi.org/10.1016/j.ymeth.2008.03.006

Aust L, Devlin B, Foster S J, et al. 2004, Yield of hu-man adipose-derived adult stem cells from liposuction aspirates. Cytotherapy, vol.6(1): 7–14. http://dx.doi.org/10.1080/14653240310004539

Zhu Y, Liu T, Song K, et al. 2008, Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochemistry and Function, vol.26(6): 664–675. http://dx.doi.org/10.1002/cbf.1488

Liao H T and Chen C T, 2014, Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells. World Journal of Stem Cells, vol.6(3): 288–295. http://dx.doi.org/10.4252/wjsc.v6.i3.288

Li Y, Charif N, Mainard D, et al. 2014, Donor's age de-pendent proliferation decrease of human bone marrow mesenchymal stem cells is linked to diminished clono-genicity. Bio-medical Material and Engineering, vol.24(Suppl 1): 47–52. http://dx.doi.org/10.3233/BME-140973

Li C Y, Wu X Y, Tong J B, et al. 2015, Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Research & Therapy, vol.6: 55. http://dx.doi.org/10.1186/s13287-015-0066-5

Gronthos S, Franklin D M, Leddy H A, et al. 2001, Sur-face protein characterization of human adipose tis-sue-derived stromal cells. Journal of Cellular Physiolo-gy, vol.189(1): 54–63. http://dx.doi.org/10.1002/jcp.1138

Festy F, Hoareau L, Bes-Houtmann S, et al. 2005, Surface protein expression between human adipose tis-sue-derived stromal cells and mature adipocytes. Histo-chemistry Cell Biology, vol.124(2): 113–121. http://dx.doi.org/10.1007/s00418-005-0014-z

Mitchell J B, McIntosh K, Zvonic S, et al. 2006, Im-munophenotype of human adipose-derived cells: tem-poral changes in stromal-associated and stem cell-asso-ciated markers. Stem Cells, vol.24(2): 376–385. http://dx.doi.org/10.1634/stemcells.2005-0234

Suga H, Matsumoto D, Eto H, et al. 2009, Functional implications of CD34 expression in human adipose-der-ived stem/progenitor cells. Stem Cells Development, vol.18(8): 1201–1210. http://dx.doi.org/10.1089/scd.2009.0003

Maumus M, Peyrafitte J A, D'Angelo R, et al. 2011, Na-tive human adipose stromal cells: localization, mor-phology and phenotype. International Journal of Obesi-ty, vol.35(9): 1141–1153. http://dx.doi.org/10.1038/ijo.2010.269

Noël D, Caton D, Roche S, et al. 2008 Cell specific dif-ferences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation po-tentials. Experimental Cell Research, vol.314(7): 1575– 1584. http://dx.doi.org/10.1016/j.yexcr.2007.12.022

Krebsbach P H, Kuznetsov SA, Satomura K, et al. 1997, Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibrob-lasts. Transplantation, vol.63(8):1059–1069. http://dx.doi.org/10.1097/00007890-199704270-00003

Sacchetti B, Funari A, Michienzi S, et al. 2007, Self- renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell, vol.131(2): 324–336. http://dx.doi.org/10.1016/j.cell.2007.08.025

Kasten P, Vogel J, Luginbuhl R, et al. 2005, Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier. Biomaterials, vol.26(29): 5879–5889. http://dx.doi.org/10.1016/j.biomaterials.2005.03.001

Mankani M H, Kuznetsov S A, Wolfe R M, et al. 2006, In vivo bone formation by human bone marrow stromal cells: reconstruction of the mouse calvarium and mandi-ble. Stem Cells, vol.24(9): 2140–2149. http://dx.doi.org/10.1634/stemcells.2005-0567

Janicki P, Boeuf S, Steck E, et al. 2011, Prediction of in vivo bone forming potency of bone marrow-derived human mesenchymal stem cells. Cells and Materials, vol.21: 488–507.

Yang M, Ma Q J, Dang G T, et al. 2005, In vitro and in vivo induction of bone formation based on ex vivo gene therapy using rat adipose-derived adult stem cells ex-pressing BMP-7. Cytotherapy, vol.7: 273-281. http://dx.doi.org/10.1080/14653240510027244

Hao W, Hu Y Y, Wei Y Y, et al. 2008, Collagen I gel can facilitate homogenous bone formation of adipose-der-ived stem cells in PLGA-beta-TCP scaffold. Cells Tis-sues Organs, vol.187(2):89–102. http://dx.doi.org/10.1159/000109946

Lin Y, Wang T, Wu L, et al. 2007, Ectopic and in situ bone formation of adipose tissue-derived stromal cells in biphasic calcium phosphate nanocomposite. Journal of Biomedical Materials Research Part A, vol. 81A(4): 900–910. http://dx.doi.org/10.1002/jbm.a.31149

Lee S J, Kang S W, Do H J, et al. 2010, Enhancement of bone regeneration by gene delivery of BMP2/Runx2 bi-cistronic vector into adipose-derived stromal cells. Bio-materials, vol.31: 5652–5659. http://dx.doi.org/10.1016/j.biomaterials.2010.03.019

Carano R A and Filvaroff E H, 2003, Angiogenesis and bone repair. Drug Discovery Today, vol.8(21): 9809. http://dx.doi.org/10.1016/S1359-6446(03)02866-6

Saran U, Gemini Piperni S and Chatterjee S, 2014, Role of angiogenesis in bone repair. Archives of Biochemistry and Biophysics, vol.561:109–117. http://dx.doi.org/10.1016/j.abb.2014.07.006

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2017-07-25