From isolation to implantation: A concise review of mesenchymal stem cell therapy in bone fracture repair

Stem Cell Research and Therapy

Volumn 5, Issue 2, 2014, Pages

  Watson, Luke ^a   Elliman, Stephen J ^a   Coleman, Cynthia M ^b  

^a Orbsen Therapeutics Ltd   (Ireland)

^b NATIONAL UNIVERSITY OF IRELAND   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; OSTEOGENIC PROTEIN 1; STROMAL CELL DERIVED FACTOR 1; VASCULOTROPIN;

ADIPOCYTE; ALLOGENEIC STEM CELL TRANSPLANTATION; AUTOLOGOUS STEM CELL TRANSPLANTATION; BONE DENSITY; BONE DEVELOPMENT; BONE GROWTH; BONE REGENERATION; BONE REMODELING; BONE STRENGTH; CELL DIFFERENTIATION; CELL ISOLATION; CELL PROLIFERATION; CELL SURFACE; DRUG MECHANISM; ENCHONDRAL OSSIFICATION; FRACTURE HEALING; FRACTURE NONUNION; HUMAN; LONG BONE; MESENCHYMAL STEM CELL TRANSPLANTATION; MINIMALLY INVASIVE PROCEDURE; NONHUMAN; OSTEOBLAST; PARACRINE SIGNALING; PRIORITY JOURNAL; REVIEW; STROMA CELL; SURVIVAL RATE; ANIMAL; FRACTURES, BONE; MOUSE; PHYSIOLOGY; PROCEDURES; WOUND HEALING;

ANIMALS; BONE REGENERATION; FRACTURES, BONE; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MICE; WOUND HEALING;

EID: 84899438602     PISSN: None     EISSN: 17576512     Source Type: Journal    
DOI: 10.1186/scrt439     Document Type: Review

References (56)

1. Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures. M Mathieu, S Rigutto, A Ingels, D Spruyt, N Stricwant, I Kharroubi, V Albarani, M Jayankura, J Rasschaert, E Bastianelli, V Gangji, Bone 2013 53 391 398 10.1016/j.bone.2013. 01.005 23318974
2. Concise review: mesenchymal stem cells and translational medicine: emerging issues. G Ren, X Chen, F Dong, W Li, X Ren, Y Zhang, Y Shi, Stem Cells Transl Med 2012 1 51 58 10.5966/sctm.2011-0019 23197640
3. Mesenchymal stem cells expressing osteogenic and angiogenic factors synergistically enhance bone formation in a mouse model of segmental bone defect. S Kumar, C Wan, G Ramaswamy, TL Clemens, S Ponnazhagan, Mol Ther 2010 18 1026 1034 10.1038/mt.2009.315 20068549
4. Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. RF Pereira, MD O'Hara, AV Laptev, KW Halford, MD Pollard, R Class, D Simon, K Livezey, DJ Prockop, Proc Natl Acad Sci U S A 1998 95 1142 1147 10.1073/pnas.95.3.1142 9448299
5. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. SP Bruder, KH Kraus, VM Goldberg, S Kadiyala, J Bone Joint Surg Am 1998 80 985 996 9698003
6. Tissue-engineered bone regeneration. H Petite, V Viateau, W Bensaïd, A Meunier, C de Pollak, M Bourguignon, K Oudina, L Sedel, G Guillemin, Nat Biotechnol 2000 18 959 963 10.1038/79449 10973216
7. Mesenchymal stem cells accelerate bone allograft incorporation in the presence of diabetes mellitus. EA Breitbart, S Meade, V Azad, S Yeh, L Al-Zube, YS Lee, J Benevenia, TL Arinzeh, SS Lin, J Orthop Res 2010 28 942 949 20058266
8. Enhancing the mesenchymal stem cell therapeutic response: cell localization and support for cartilage repair. SE Bulman, V Barron, CM Coleman, F Barry, Tissue Eng Part B Rev 2013 19 58 68 10.1089/ten.teb.2012.0101 22897343
9. Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical sized segmental tibial bone defects in aged sheep. A Berner, JC Reichert, MA Woodruff, S Saifzadeh, AJ Morris, DR Epari, M Nerlich, MA Schuetz, DW Hutmacher, Acta Biomater 2013 9 7874 7884 10.1016/j.actbio.2013. 04.035 23628773
10. De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model. W Bensaïd, K Oudina, V Viateau, E Potier, V Bousson, C Blanchat, L Sedel, G Guillemin, H Petite, Tissue Eng 2005 11 814 824 10.1089/ten.2005.11.814 15998221
11. Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae. A Cipitria, JC Reichert, DR Epari, S Saifzadeh, A Berner, H Schell, M Mehta, MA Schuetz, GN Duda, DW Hutmacher, Biomaterials 2013 34 9960 9968 10.1016/j.biomaterials.2013.09.011 24075478
12. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues, Cloning in vitro and retransplantation in vivo. AJ Friedenstein, RK Chailakhyan, NV Latsinik, AF Panasyuk, IV Keiliss-Borok, Transplantation 1974 17 331 340 10.1097/00007890-197404000-00001 4150881
13. How do mesenchymal stromal cells exert their therapeutic benefit? EM Horwitz, M Dominici, Cytotherapy 2008 10 771 774 10.1080/14653240802618085 19089685
14. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. B Sacchetti, A Funari, S Michienzi, S Di Cesare, S Piersanti, I Saggio, E Tagliafico, S Ferrari, PG Robey, M Riminucci, P Bianco, Cell 2007 131 324 336 10.1016/j.cell.2007.08.025 17956733
15. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. S Morikawa, Y Mabuchi, Y Kubota, Y Nagai, K Niibe, E Hiratsu, S Suzuki, C Miyauchi-Hara, N Nagoshi, T Sunabori, S Shimmura, A Miyawaki, T Nakagawa, T Suda, H Okano, Y Matsuzaki, J Exp Med 2009 206 2483 2496 10.1084/jem.20091046 19841085
16. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Y Omatsu, T Sugiyama, H Kohara, G Kondoh, N Fujii, K Kohno, T Nagasawa, Immunity 2010 33 387 399 10.1016/j.immuni.2010.08.017 20850355
17. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. S Méndez-Ferrer, TV Michurina, F Ferraro, AR Mazloom, BD Macarthur, SA Lira, DT Scadden, A Ma'ayan, GN Enikolopov, PS Frenette, Nature 2010 466 829 834 10.1038/nature09262 20703299
18. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. A Greenbaum, YM Hsu, RB Day, LG Schuettpelz, MJ Christopher, JN Borgerding, T Nagasawa, DC Link, Nature 2013 495 227 230 10.1038/nature11926 23434756
19. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. D Park, JA Spencer, BI Koh, T Kobayashi, J Fujisaki, TL Clemens, CP Lin, HM Kronenberg, DT Scadden, Cell Stem Cell 2012 10 259 272 10.1016/j.stem.2012.02.003 22385654
20. Depletion of stromal cells expressing fibroblast activation protein-alpha from skeletal muscle and bone marrow results in cachexia and anemia. EW Roberts, A Deonarine, JO Jones, AE Denton, C Feig, SK Lyons, M Espeli, M Kraman, B McKenna, RJ Wells, Q Zhao, OL Caballero, R Larder, AP Coll, S O'Rahilly, KM Brindle, SA Teichmann, DA Tuveson, DT Fearon, J Exp Med 2013 210 1137 1151 10.1084/jem.20122344 23712428
21. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. E Tran, D Chinnasamy, Z Yu, RA Morgan, CC Lee, NP Restifo, SA Rosenberg, J Exp Med 2013 210 1125 1135 10.1084/jem.20130110 23712432
22. Human bone marrow mesenchymal stem cells in vivo. E Jones, D McGonagle, Rheumatology (Oxford) 2008 47 126 131
23. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. A Tormin, O Li, JC Brune, S Walsh, B Schütz, M Ehinger, N Ditzel, M Kassem, S Scheding, Blood 2011 117 5067 5077 10.1182/blood-2010-08-304287 21415267
24. A perivascular origin for mesenchymal stem cells in multiple human organs. M Crisan, S Yap, L Casteilla, CW Chen, M Corselli, TS Park, G Andriolo, B Sun, B Zheng, L Zhang, C Norotte, PN Teng, J Traas, R Schugar, BM Deasy, S Badylak, HJ Buhring, JP Giacobino, L Lazzari, J Huard, B Péault, Cell Stem Cell 2008 3 301 313 10.1016/j.stem.2008.07.003 18786417
25. Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. Y Nakamura, F Arai, H Iwasaki, K Hosokawa, I Kobayashi, Y Gomei, Y Matsumoto, H Yoshihara, T Suda, Blood 2010 116 1422 1432 10.1182/blood-2009-08-239194 20472830
26. Perivascular support of human hematopoietic stem/progenitor cells. M Corselli, CJ Chin, C Parekh, A Sahaghian, W Wang, S Ge, D Evseenko, X Wang, E Montelatici, L Lazzari, GM Crooks, B Péault, Blood 2013 121 2891 2901 10.1182/blood-2012-08-451864 23412095
27. The role of chemokines in mesenchymal stem cell homing to myocardium. Y Wu, RC Zhao, Stem Cell Rev 2012 8 243 250 10.1007/s12015-011-9293-z 21706142
28. Cytokines and hematopoietic stem cell mobilization. B Nervi, DC Link, JF DiPersio, J Cell Biochem 2006 99 690 705 10.1002/jcb.21043 16888804
29. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. H Liu, S Liu, Y Li, X Wang, W Xue, G Ge, X Luo, PLoS One 2012 7 34608 10.1371/journal.pone.0034608 22511954
30. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. T Kitaori, H Ito, EM Schwarz, R Tsutsumi, H Yoshitomi, S Oishi, M Nakano, N Fujii, T Nagasawa, T Nakamura, Arthritis Rheum 2009 60 813 823 10.1002/art.24330 19248097
31. Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources. H Ito, Mod Rheumatol 2011 21 113 121 10.3109/s10165-010-0357-8 20830500
32. The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model. K Taguchi, R Ogawa, M Migita, H Hanawa, H Ito, H Orimo, Biochem Biophys Res Commun 2005 331 31 36 10.1016/j.bbrc.2005.03.119 15845353
33. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. RF Pereira, KW Halford, MD O'Hara, DB Leeper, BP Sokolov, MD Pollard, O Bagasra, DJ Prockop, Proc Natl Acad Sci U S A 1995 92 4857 4861 10.1073/pnas.92.11.4857 7761413
34. Cells capable of bone production engraft from whole bone marrow transplants in nonablated mice. SK Nilsson, MS Dooner, HU Weier, B Frenkel, JB Lian, GS Stein, PJ Quesenberry, J Exp Med 1999 189 729 734 10.1084/jem.189.4.729 9989988
35. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. F Granero-Moltó JA Weis, MI Miga, B Landis, TJ Myers, L O'Rear, L Longobardi, ED Jansen, DP Mortlock, A Spagnoli, Stem Cells 2009 27 1887 1898 10.1002/stem.103 19544445
36. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. EM Horwitz, DJ Prockop, LA Fitzpatrick, WW Koo, PL Gordon, M Neel, M Sussman, P Orchard, JC Marx, RE Pyeritz, MK Brenner, Nat Med 1999 5 309 313 10.1038/6529 10086387
37. Systemically delivered insulin-like growth factor-I enhances mesenchymal stem cell-dependent fracture healing. TJ Myers, Y Yan, F Granero-Molto, JA Weis, L Longobardi, T Li, Y Li, C Contaldo, H Ozkan, A Spagnoli, Growth Factors 2012 30 230 241 10.3109/08977194.2012.683188 22559791
38. The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats. G Burastero, S Scarfì C Ferraris, C Fresia, N Sessarego, F Fruscione, F Monetti, F Scarfò P Schupbach, M Podestà G Grappiolo, E Zocchi, Bone 2010 47 117 126 10.1016/j.bone.2010.03.023 20362702
39. The development of tissue-engineered bone of different origin through endochondral and intramembranous ossification following the implantation of mesenchymal stem cells and osteoblasts in a murine model. F Tortelli, R Tasso, F Loiacono, R Cancedda, Biomaterials 2010 31 242 249 10.1016/j.biomaterials.2009. 09.038 19796807
40. Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. C Scotti, B Tonnarelli, A Papadimitropoulos, A Scherberich, S Schaeren, A Schauerte, J Lopez-Rios, R Zeller, A Barbero, I Martin, Proc Natl Acad Sci U S A 2010 107 7251 7256 10.1073/pnas.1000302107 20406908
41. Engineering of a functional bone organ through endochondral ossification. C Scotti, E Piccinini, H Takizawa, A Todorov, P Bourgine, A Papadimitropoulos, A Barbero, MG Manz, I Martin, Proc Natl Acad Sci U S A 2013 110 3997 4002 10.1073/pnas.1220108110 23401508
42. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. L von Bahr, I Batsis, G Moll, M Hägg, A Szakos, B Sundberg, M Uzunel, O Ringden, K Le Blanc, Stem Cells 2012 30 1575 1578 10.1002/stem.1118 22553154
43. Microarray analysis of gene expression during the inflammation and endochondral bone formation stages of rat femur fracture repair. CH Rundle, H Wang, H Yu, RB Chadwick, EI Davis, JE Wergedal, KH Lau, S Mohan, JT Ryaby, DJ Baylink, Bone 2006 38 521 529 10.1016/j.bone.2005.09.015 16321582
44. Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption. LC Gerstenfeld, TJ Cho, T Kon, T Aizawa, A Tsay, J Fitch, GL Barnes, DT Graves, TA Einhorn, J Bone Miner Res 2003 18 1584 1592 10.1359/jbmr.2003.18.9.1584 12968667
45. High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing. J Alblowi, RA Kayal, M Siqueira, E McKenzie, N Krothapalli, J McLean, J Conn, B Nikolajczyk, TA Einhorn, L Gerstenfeld, DT Graves, Am J Pathol 2009 175 1574 1585 10.2353/ajpath.2009. 090148 19745063
46. Developmental Committee of the European Group for Blood and Marrow Transplantation: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. K Le Blanc, F Frassoni, L Ball, F Locatelli, H Roelofs, I Lewis, E Lanino, B Sundberg, ME Bernardo, M Remberger, G Dini, RM Egeler, A Bacigalupo, W Fibbe, O Ringdén, Lancet 2008 371 1579 1586 10.1016/S0140-6736(08)60690-X 18468541
47. The origin of bone formed in composite grafts of porous calcium phosphate ceramic loaded with marrow cells. J Goshima, VM Goldberg, AI Caplan, Clin Orthop Relat Res 1991 269 274 283 1650657
48. The recruitment of two consecutive and different waves of host stem/progenitor cells during the development of tissue-engineered bone in a murine model. R Tasso, F Fais, D Reverberi, F Tortelli, R Cancedda, Biomaterials 2010 31 2121 2129 10.1016/j.biomaterials.2009.11.064 20004968
49. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. HM Lazarus, SE Haynesworth, SL Gerson, NS Rosenthal, AI Caplan, Bone Marrow Transplant 1995 16 557 564 8528172
50. Repair of large bone defects with the use of autologous bone marrow stromal cells. R Quarto, M Mastrogiacomo, R Cancedda, SM Kutepov, V Mukhachev, A Lavroukov, E Kon, M Marcacci, N Engl J Med 2001 344 385 386 10.1056/NEJM200102013440516 11195802
51. Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. M Marcacci, E Kon, V Moukhachev, A Lavroukov, S Kutepov, R Quarto, M Mastrogiacomo, R Cancedda, Tissue Eng 2007 13 947 955 10.1089/ten.2006.0271 17484701
52. Tissue engineering approach to the treatment of bone tumors: three cases of cultured bone grafts derived from patients' mesenchymal stem cells. T Morishita, K Honoki, H Ohgushi, N Kotobuki, A Matsushima, Y Takakura, Artif Organs 2006 30 115 118 10.1111/j.1525-1594.2006.00190.x 16433845
53. Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study. M Liebergall, J Schroeder, R Mosheiff, Z Gazit, Z Yoram, L Rasooly, A Daskal, A Khoury, Y Weil, S Beyth, Mol Ther 2013 21 1631 1638 10.1038/mt.2013.109 23732992
54. Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment. S Giannotti, L Trombi, V Bottai, M Ghilardi, D D'Alessandro, S Danti, G Dell'Osso, G Guido, M Petrini, PLoS One 2013 8 73893 10.1371/journal.pone.0073893 24023694
55. In vivo implanted bone marrow-derived mesenchymal stem cells trigger a cascade of cellular events leading to the formation of an ectopic bone regenerative niche. R Tasso, V Ulivi, D Reverberi, C Lo Sicco, F Descalzi, R Cancedda, Stem Cells Dev 2013 22 3178 3191 10.1089/scd.2013.0313 23924051
56. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. P Hernigou, A Poignard, F Beaujean, H Rouard, J Bone Joint Surg Am 2005 87 1430 1437 10.2106/JBJS.D.02215 15995108