Skip to main content
SpringerLink
Log in

In Situ Targeting of Stem and Progenitor Cells in Native Tissues

  • Chapter
  • First Online:
Orthobiologics

  • 1606 Accesses

Abstract

Tissue repair/regeneration in all native tissues involves a process of activation, proliferation, and migration of heterogeneous stem and progenitor cell populations. These cells may be resident in local tissues or recruited from systemic circulation. Much of the recent focus of cell-based regenerative therapies has been based on the premise that the concentration and prevalence of local stem and progenitor cells are deficient and must be enhanced by providing exogenous cells that have been expanded ex vivo (e.g., mesenchymal stromal cells).

Targeting local activation of stem and progenitor populations or activation of homing signals that recruit circulating cells to a site of injury or repair has long been recognized as a more direct and potentially more effective and less expensive strategy. Recent studies have identified mechanisms of how to mobilize and home stem and progenitor cells into the peripheral blood and potentially accelerate tissue repair/regeneration. This approach is advantageous over the cell-based therapy as it does not require the costly, time-consuming ex vivo cell expansion process, thus resulting in shorter recovery time. Pre-clinical studies testing this novel strategy have provided promising results. In this chapter, we introduce the molecules which can mobilize stem and progenitor cells from the bone marrow to the peripheral blood, recruit them to the damaged tissue, and differentiate them to the target cells, respectively. These molecules may have the potential to treat orthopedic diseases as a future therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Muschler GF, Nakamoto C, Griffith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am. 2004;86(7):1541–58.

    Article  PubMed  Google Scholar 

  2. Kwee E, Saidel G, Powell K, Heylman C, Boehm C, Muschler G. Quantifying proliferative and surface marker heterogeneity in colony-founding connective tissue progenitors and their progeny using time-lapse microscopy. J Tissue Eng Regen Med. 2019;13(2):203–16.

    CAS  PubMed  Google Scholar 

  3. Mantripragada VP, Piuzzi NS, Bova WA, Boehm C, Obuchowski NA, Lefebvre V, et al. Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad, synovium, and periosteum—implications for cartilage repair. Connect Tissue Res. 2019;60(6):597–610.

    Article  CAS  PubMed  Google Scholar 

  4. Muschler GF, Midura RJ, Nakamoto C. Practical modeling concepts for connective tissue stem cell and progenitor compartment kinetics. J Biomed Biotechnol. 2003;2003(3):170–93.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Krafts KP. Tissue repair. Organogenesis. 2010;6(4):225–33.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liu J, Saul D, Böker KO, Ernst J, Lehman W, Schilling AF. Current methods for skeletal muscle tissue repair and regeneration. Biomed Res Int. 2018;2018:1–11.

    Google Scholar 

  7. Miller LW. New strategies to enhance stem cell homing for tissue repair. Stem Cell Gene Ther Cardiovasc Dis. 2016:485–96.

    Google Scholar 

  8. Szczesny SE, Lee CS, Soslowsky LJ. Remodeling and repair of orthopedic tissue: role of mechanical loading and biologics. Am J Orthop. 2018;13

    Google Scholar 

  9. Tsiridis E, Upadhyay N, Giannoudis P. Molecular aspects of fracture healing: which are the important molecules? Injury. 2007;38(1):S11–25.

    Article  PubMed  Google Scholar 

  10. Berebichez-Fridman R, Gómez-García R, Granados-Montiel J, Berebichez-Fastlicht E, Olivos-Meza A, Granados J, et al. The holy grail of orthopedic surgery: mesenchymal stem cells—their current uses and potential applications. Stem Cells Int. 2017;2017:1–14.

    Article  CAS  Google Scholar 

  11. Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4(1):22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Caplan Arnold I, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012;10(6):709–16.

    Article  CAS  PubMed  Google Scholar 

  14. Chen F-M, Wu L-A, Zhang M, Zhang R, Sun H-H. Homing of endogenous stem/progenitor cells for in situ tissue regeneration: promises, strategies, and translational perspectives. Biomaterials. 2011;32(12):3189–209.

    Article  CAS  PubMed  Google Scholar 

  15. Ito H. Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources. Mod Rheumatol. 2011;21(2):113–21.

    Article  CAS  PubMed  Google Scholar 

  16. Eghbali-Fatourechi GZ, Nagel D. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005;8

    Google Scholar 

  17. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. Circulating skeletal stem cells. J Cell Biol. 2001;153(5):1133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res Ther. 2000;2(6):477.

    Article  CAS  Google Scholar 

  19. Kumagai K, Vasanji A, Drazba JA, Butler RS, Muschler GF. Circulating cells with osteogenic potential are physiologically mobilized into the fracture healing site in the parabiotic mice model. J Orthop Res. 2008;26(2):165–75.

    Article  PubMed  Google Scholar 

  20. Otsuru S, Tamai K, Yamazaki T, Yoshikawa H, Kaneda Y. Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells. 2008;26(1):223–34.

    Article  CAS  PubMed  Google Scholar 

  21. Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45–54.

    Article  PubMed  Google Scholar 

  22. Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42(6):551–5.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Phillips AM. Overview of the fracture healing cascade. Injury. 2005;36(3):S5–7.

    Article  PubMed  Google Scholar 

  24. Shirley D, Marsh D, Jordan G, McQuaid S, Li G. Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res. 2005;23(5):1013–21.

    Article  PubMed  Google Scholar 

  25. Yellowley C. CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair. Bonekey Rep. 2013;2:300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Gunawardene P, Al Saedi A, Singh L, Bermeo S, Vogrin S, Phu S, et al. Age, gender, and percentage of circulating osteoprogenitor (COP) cells: the COP study. Exp Gerontol. 2017;96:68–72.

    Article  PubMed  Google Scholar 

  27. Pignolo RJ, Kassem M. Circulating osteogenic cells: implications for injury, repair, and regeneration. J Bone Miner Res. 2011;26(8):1685–93.

    Article  CAS  PubMed  Google Scholar 

  28. Rochefort GY, Delorme B, Lopez A, Hérault O, Bonnet P, Charbord P, et al. Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells. 2006;24(10):2202–8.

    Article  CAS  PubMed  Google Scholar 

  29. Crane GM, Jeffery E, Morrison SJ. Adult haematopoietic stem cell niches. Nat Rev Immunol. 2017;17(9):573–90.

    Article  CAS  PubMed  Google Scholar 

  30. Tay J, Levesque J-P, Winkler IG. Cellular players of hematopoietic stem cell mobilization in the bone marrow niche. Int J Hematol. 2017;105(2):129–40.

    Article  CAS  PubMed  Google Scholar 

  31. Pessach I, Resnick I, Shimoni A, Nagler A. G-CSF-primed BM for allogeneic SCT: revisited. Bone Marrow Transplant. 2015;50(7):892–8.

    Article  CAS  PubMed  Google Scholar 

  32. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005;201(8):1307–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Katayama Y, Battista M, Kao W-M, Hidalgo A, Peired AJ, Thomas SA, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124(2):407–21.

    Article  CAS  PubMed  Google Scholar 

  34. Lévesque J-P, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Investig. 2003;111(2):187–96.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Tzeng Y-S, Li H, Kang Y-L, Chen W-C, Cheng W-C, Lai D-M. Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. Blood. 2011;117(2):429–39.

    Article  CAS  PubMed  Google Scholar 

  36. Pitchford SC, Furze RC, Jones CP, Wengner AM, Rankin SM. Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell. 2009;4(1):62–72.

    Article  CAS  PubMed  Google Scholar 

  37. Toupadakis CA, Granick JL, Sagy M, Wong A, Ghassemi E, Chung D-J, et al. Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model. Cytotherapy. 2013;15(9):1136–47.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kumar S, Ponnazhagan S. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mous e model of segmental bone defect. Bone. 2012;50(4):1012–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Meeson R, Sanghani-Keri A, Coathup M, Blunn G. VEGF with AMD3100 endogenously mobilizes mesenchymal stem cells and improves fracture healing. J Orthop Res. 2019;37(6):1294–302.

    Article  CAS  PubMed  Google Scholar 

  40. Bianchi ME, Crippa MP, Manfredi AA, Mezzapelle R, Querini PR, Venereau E. High-mobility group box 1 protein orchestrates responses to tissue damage via inflammation, innate and adaptive immunity, and tissue repair. Immunol Rev. 2017;280(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  41. Palumbo R, Galvez BG, Pusterla T, De Marchis F, Cossu G, Marcu KB, et al. Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation. J Cell Biol. 2007;179(1):33–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, et al. Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab. 2008;28(5):927–38.

    Article  CAS  PubMed  Google Scholar 

  43. Straino S, Di Carlo A, Mangoni A, De Mori R, Guerra L, Maurelli R, et al. High-mobility group box 1 protein in human and murine skin: involvement in wound healing. J Investig Dermatol. 2008;128(6):1545–53.

    Article  CAS  PubMed  Google Scholar 

  44. Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, et al. PDGFR-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci. 2011;108(16):6609–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chavakis E, Hain A, Vinci M, Carmona G, Bianchi ME, Vajkoczy P, et al. High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells. Circ Res. 2007;100(2):204–12.

    Article  CAS  PubMed  Google Scholar 

  46. Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells: a prerequisite for cell therapy. J Mol Cell Cardiol. 2008;45(4):514–22.

    Article  CAS  PubMed  Google Scholar 

  47. Palumbo R, Bianchi ME. High mobility group box 1 protein, a cue for stem cell recruitment. Biochem Pharmacol. 2004;68(6):1165–70.

    Article  CAS  PubMed  Google Scholar 

  48. Aikawa E, Fujita R, Kikuchi Y, Kaneda Y, Tamai K. Systemic high-mobility group box 1 administration suppresses skin inflammation by inducing an accumulation of PDGFRα+ mesenchymal cells from bone marrow. Sci Rep. 2015;5(1):11,008.

    Article  CAS  Google Scholar 

  49. Goto T, Miyagawa S, Tamai K, Matsuura R, Kido T, Kuratani T, et al. High-mobility group box 1 fragment suppresses adverse post-infarction remodeling by recruiting PDGFRα-positive bone marrow cells. PLoS One. 2020;15(4):e0230392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kido T, Miyagawa S, Goto T, Tamai K, Ueno T, Toda K, et al. The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster. PLoS One. 2018;13(12):e0202838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lin F, Xue D, Xie T, Pan Z. HMGB1 promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via Rap1 activation. Mol Med Rep. 2016;14(2):1283–9.

    Article  CAS  PubMed  Google Scholar 

  52. Lin F, Zhang W, Xue D, Zhu T, Li J, Chen E, et al. Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. Int J Mol Med. 2016;37(3):789–97.

    Article  CAS  PubMed  Google Scholar 

  53. Meng E, Guo Z, Wang H, Jin J, Wang J, Wang H, et al. High mobility group box 1 protein inhibits the proliferation of human mesenchymal stem cells and promotes their migration and differentiation along osteoblastic pathway. Stem Cells Dev. 2008;17(4):805–14.

    Article  CAS  PubMed  Google Scholar 

  54. Lv Y, Lin C. High mobility group box 1-immobilized nanofibrous scaffold enhances vascularization, osteogenesis and stem cell recruitment. J Mater Chem B. 2016;4(29):5002–14.

    Article  CAS  PubMed  Google Scholar 

  55. Xue D, Zhang W, Chen E, Gao X, Liu L, Ye C, et al. Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing. Oncotarget. 2017;8(26):42,098–115.

    Article  Google Scholar 

  56. Xie H-L, Zhang Y, Huang Y-Z, Li S, Wu C-G, Jiao X-F, et al. Regulation of high mobility group box 1 and hypoxia in the migration of mesenchymal stem cells. Cell Biol Int. 2014;38(7):892–7.

    Article  CAS  PubMed  Google Scholar 

  57. Hong HS, Lee J, Lee E, Kwon YS, Lee E, Ahn W, et al. A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells. Nat Med. 2009;15(4):425–35.

    Article  CAS  PubMed  Google Scholar 

  58. Onuoha GN. Circulating sensory peptide levels within 24 h of human bone fracture. Peptides. 2001;22(7):1107–10.

    Article  CAS  PubMed  Google Scholar 

  59. Onuoha GN, Alpar EK. Elevation of plasma CGRP and SP levels in orthopedic patients with fracture neck of femur. Neuropeptides. 2000;34(2):116–20.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang Y, An S, Hao J, Tian F, Fang X, Wang J. Systemic injection of substance P promotes murine calvarial repair through mobilizing endogenous mesenchymal stem cells. Sci Rep. 2018;8(1):12996.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Hausman MR, Schaffler MB, Majeska RJ. Prevention of fracture healing in rats by an inhibitor of angiogenesis. Bone. 2001;29(6):560–4.

    Article  CAS  PubMed  Google Scholar 

  62. Lu C, Saless N, Wang X, Sinha A, Decker S, Kazakia G, et al. The role of oxygen during fracture healing. Bone. 2013;52(1):220–9.

    Article  CAS  PubMed  Google Scholar 

  63. Stegen S, van Gastel N, Carmeliet G. Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration. Bone. 2015;70:19–27.

    Article  CAS  PubMed  Google Scholar 

  64. Atesok K, Li R, Stewart DJ, Schemitsch EH. Endothelial progenitor cells promote fracture healing in a segmental bone defect model. J Orthop Res. 2010;28(8):1007–14.

    Article  PubMed  Google Scholar 

  65. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999;18(14):3964–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Keramaris NC, Calori GM, Nikolaou VS, Schemitsch EH, Giannoudis PV. Fracture vascularity and bone healing: a systematic review of the role of VEGF. Injury. 2008;39:S45–57.

    Article  PubMed  Google Scholar 

  67. Street J, Bao M, de Guzman L, Bunting S, Peale FV, Ferrara N, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci. 2002;99(15):9656–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jujo K, Ii M, Sekiguchi H, Klyachko E, Misener S, Tanaka T, et al. CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase–dependent mechanism. Circulation. 2013;127(1):63–73.

    Article  CAS  PubMed  Google Scholar 

  69. Petit I, Jin D, Rafii S. The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28(7):299–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–6.

    Article  CAS  PubMed  Google Scholar 

  71. Stroncek DF, Clay ME, Herr G, Smith J, Jaszcz WB, Ilstrup S, et al. The kinetics of G-CSF mobilization of CD34+ cells in healthy people. Transfus Med. 1997;7(1):19–24.

    Article  CAS  PubMed  Google Scholar 

  72. Herrmann M, Zeiter S, Eberli U, Hildebrand M, Camenisch K, Menzel U, et al. Five days granulocyte Colony-stimulating factor treatment increases bone formation and reduces gap size of a rat segmental bone defect: a pilot study. Front Bioeng Biotechnol. 2018;6:5.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kuroda R, Matsumoto T, Kawakami Y, Fukui T, Mifune Y, Kurosaka M. Clinical impact of circulating CD34-positive cells on bone regeneration and healing. Tissue Eng Part B Rev. 2014;20(3):190–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kuroda R, Matsumoto T, Miwa M, Kawamoto A, Mifune Y, Fukui T, et al. Local transplantation of G-CSF-mobilized CD34+ cells in a patient with tibial nonunion: a case report. Cell Transplant. 2011;20(9):1491–6.

    Article  PubMed  Google Scholar 

  75. Kuroda R, Matsumoto T, Niikura T, Kawakami Y, Fukui T, Lee SY, et al. Local transplantation of granulocyte colony stimulating factor-mobilized CD34+ cells for patients with femoral and tibial nonunion: pilot clinical trial. Stem Cells Transl Med. 2014;3(1):128–34.

    Article  CAS  PubMed  Google Scholar 

  76. Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell. 2009;4(3):206–16.

    Article  CAS  PubMed  Google Scholar 

  77. Hu C, Yong X, Li C, Lü M, Liu D, Chen L, et al. CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair. J Surg Res. 2013;183(1):427–34.

    Article  CAS  PubMed  Google Scholar 

  78. Iinuma S, Aikawa E, Tamai K, Fujita R, Kikuchi Y, Chino T, et al. Transplanted bone marrow–derived circulating PDGFRα + cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft. J Immunol. 2015;194(4):1996–2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kitaori T, Ito H, Schwarz EM, Tsutsumi R, Yoshitomi H, Oishi S, et al. 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. Arthritis Rheum. 2009;60(3):813–23.

    Article  CAS  PubMed  Google Scholar 

  80. Xu J, Chen Y, Liu Y, Zhang J, Kang Q, Ho K, et al. Effect of SDF-1/Cxcr4 signaling antagonist AMD3100 on bone mineralization in distraction osteogenesis. Calcif Tissue Int. 2017;100(6):641–52.

    Article  CAS  PubMed  Google Scholar 

  81. Ponte AL, Marais E, Gallay N, Langonné A, Delorme B, Hérault O, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells. 2007;25(7):1737–45.

    Article  CAS  PubMed  Google Scholar 

  82. Toupadakis CA, Wong A, Genetos DC, Chung D-J, Murugesh D, Anderson MJ, et al. Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair. J Orthop Res. 2012;30(11):1853–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Higashino K, Viggeswarapu M, Bargouti M, Liu H, Titus L, Boden SD. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation. Tissue Eng Part A. 2011;17(3–4):523–30.

    Article  CAS  PubMed  Google Scholar 

  84. Shinohara K, Greenfield S, Pan H, Vasanji A, Kumagai K, Midura RJ, et al. Stromal cell-derived factor-1 and monocyte chemotactic protein-3 improve recruitment of osteogenic cells into sites of musculoskeletal repair. J Orthop Res. 2011;29(7):1064–9.

    Article  CAS  PubMed  Google Scholar 

  85. Roberts SJ, Ke HZ. Anabolic strategies to augment bone fracture healing. Curr Osteoporos Rep. 2018;16(3):289–98.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84(12):2123–34.

    Article  PubMed  Google Scholar 

  87. Swiontkowski MF. Recombinant human bone morphogenetic protein-2 in open tibial fractures: a subgroup analysis of data combined from two prospective randomized studies. Yearbook Orthop. 2007;2007:89.

    Article  Google Scholar 

  88. Wei S, Cai X, Huang J, Xu F, Liu X, Wang Q. Recombinant human BMP-2 for the treatment of open tibial fractures. Orthopedics. 2012;35(6):e847–54.

    Article  PubMed  Google Scholar 

  89. Kawaguchi H, Oka H, Jingushi S, Izumi T, Fukunaga M, Sato K, et al. A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: a randomized, placebo-controlled trial. J Bone Miner Res. 2010;25(12):2735–43.

    Article  PubMed  CAS  Google Scholar 

  90. Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, et al. Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res. 2010;25(2):404–14.

    Article  CAS  PubMed  Google Scholar 

  91. Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011;93(17):1583–7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA

    Cierra A. Clark, Takeshi Oichi, Joshua M. Abzug & Satoru Otsuru

Authors
  1. Cierra A. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Oichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joshua M. Abzug
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoru Otsuru
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoru Otsuru .

Editor information

Editors and Affiliations

  1. Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Filardo

  2. Orthopaedic & Sports Medicine Group, Santa Monica Orthopaedic & Sports Medicine, Santa Monica, CA, USA

    Bert R. Mandelbaum

  3. Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    George F. Muschler

  4. Hospital for Special Surgery, New York, NY, USA

    Scott A. Rodeo

  5. Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan

    Norimasa Nakamura

Rights and permissions

Reprints and permissions

Copyright information

© 2022 ISAKOS

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Clark, C.A., Oichi, T., Abzug, J.M., Otsuru, S. (2022). In Situ Targeting of Stem and Progenitor Cells in Native Tissues. In: Filardo, G., Mandelbaum, B.R., Muschler, G.F., Rodeo, S.A., Nakamura, N. (eds) Orthobiologics. Springer, Cham. https://doi.org/10.1007/978-3-030-84744-9_32

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-84744-9_32

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-84743-2

  • Online ISBN: 978-3-030-84744-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation