Skip to main content

Advertisement

SpringerLink
Log in

Modulation of the Immune System Promotes Tissue Regeneration

  • Review
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

The immune system plays an essential role in the angiogenesis, repair, and regeneration of damaged tissues. Therefore, the design of scaffolds that manipulate immune cells and factors in such a way that could accelerate the repair of damaged tissues, following implantation, is one of the main goals of regenerative medicine. However, before manipulating the immune system, the function of the various components of the immune system during the repair process should be well understood and the fabrication conditions of the manipulated scaffolds should be brought closer to the physiological state of the body. In this article, we first review the studies aimed at the role of distinct immune cell populations in angiogenesis and support of damaged tissue repair. In the second part, we discuss the use of strategies that promote tissue regeneration by modulating the immune system. Given that various studies have shown an increase in tissue repair rate with the addition of stem cells and growth factors to the scaffolds, and regarding the limited resources of stem cells, we suggest the design of scaffolds that are capable to develop repair of damaged tissue by manipulating the immune system and create an alternative for repair strategies that use stem cells or growth factors.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ellis, S., Lin, E. J., & Tartar, D. (2018). Immunology of wound healing. Current Dermatology Reports, 7, 350–358.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Peng, Y., Martin, D. A., Kenkel, J., Zhang, K., Ogden, C. A., & Elkon, K. B. (2007). Innate and adaptive immune response to apoptotic cells. Journal of Autoimmunity, 29, 303–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Otis, J. S., Niccoli, S., Hawdon, N., Sarvas, J. L., Frye, M. A., Chicco, A. J., & Lees, S. J. (2014). Pro-inflammatory mediation of myoblast proliferation. PLoS ONE, 9, e92363.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Frantz, S., Vincent, K. A., Feron, O., & Kelly, R. A. (2005). Innate immunity and angiogenesis. Circulation Research, 96, 15–26.

    Article  CAS  PubMed  Google Scholar 

  5. Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140, 805–820.

    Article  CAS  PubMed  Google Scholar 

  6. Kawai, T., & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nature Immunology, 11, 373.

    Article  CAS  PubMed  Google Scholar 

  7. Li, T., et al. (2018). 3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone. Acta biomaterialia, 71, 96–107.

    Article  CAS  PubMed  Google Scholar 

  8. Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews Immunology, 13, 159–175.

    Article  CAS  PubMed  Google Scholar 

  9. Sadtler, K., et al. (2016). Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science, 352, 366–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Swinehart, I. T., & Badylak, S. F. (2016). Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis. Developmental Dynamics, 245, 351–360. https://doi.org/10.1002/dvdy.24379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Londono, R., & Badylak, S. F. (2015). Biologic scaffolds for regenerative medicine: Mechanisms of in vivo remodeling. Annals of Biomedical Engineering, 43, 577–592.

    Article  PubMed  Google Scholar 

  12. Ben-Shaul, S., Landau, S., Merdler, U., & Levenberg, S. (2019). Mature vessel networks in engineered tissue promote graft–host anastomosis and prevent graft thrombosis. Proceedings of the National Academy of Sciences USA, 116, 2955–2960.

    Article  CAS  Google Scholar 

  13. Chen, R. R., Silva, E. A., Yuen, W. W., & Mooney, D. J. (2007). Spatio–temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharmaceutical Research, 24, 258–264.

    Article  PubMed  CAS  Google Scholar 

  14. Freeman, I., & Cohen, S. (2009). The influence of the sequential delivery of angiogenic factors from affinity-binding alginate scaffolds on vascularization. Biomaterials, 30, 2122–2131.

    Article  CAS  PubMed  Google Scholar 

  15. Spiller, K. L., et al. (2015). Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials, 37, 194–207.

    Article  CAS  PubMed  Google Scholar 

  16. Perry, L., Flugelman, M. Y., & Levenberg, S. (2017). Elderly patient-derived endothelial cells for vascularization of engineered muscle. Molecular Therapy, 25, 935–948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Christoffersson, G., et al. (2012). VEGF-A recruits a proangiogenic MMP-9–delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue Blood. The Journal of the American Society of Hematology, 120, 4653–4662.

    CAS  Google Scholar 

  18. Vinish, M., Cui, W., Stafford, E., Bae, L., Hawkins, H., Cox, R., & Toliver-Kinsky, T. (2016). Dendritic cells modulate burn wound healing by enhancing early proliferation. Wound Repair and Regeneration, 24, 6–13.

    Article  PubMed  Google Scholar 

  19. Gregorio, J., et al. (2010). Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. Journal of Experimental Medicine, 207, 2921–2930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wilgus, T. A., Roy, S., & McDaniel, J. C. (2013). Neutrophils and wound repair: Positive actions and negative reactions. Advances in Wound Care, 2, 379–388.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zemans, R. L., et al. (2011). Neutrophil transmigration triggers repair of the lung epithelium via β-catenin signaling. Proceedings of the National Academy of Sciences USA, 108, 15990–15995.

    Article  CAS  Google Scholar 

  22. Elliott, M. R., Koster, K. M., & Murphy, P. S. (2017). Efferocytosis signaling in the regulation of macrophage inflammatory responses. The Journal of Immunology, 198, 1387–1394.

    Article  CAS  PubMed  Google Scholar 

  23. Brancato, S. K., & Albina, J. E. (2011). Wound macrophages as key regulators of repair: Origin, phenotype, and function. The American Journal of Pathology, 178, 19–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sindrilaru, A., et al. (2011). An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. The Journal of Clinical Investigation, 121, 985–997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Foroughi, K., Khaksari, M., Rahmati, M., Bitaraf, F. S., & Shayannia, A. (2019). Apelin-13 protects PC12 cells against methamphetamine-induced oxidative stress, autophagy and apoptosis. Neurochemical Research, 44, 2103–2112. https://doi.org/10.1007/s11064-019-02847-9

    Article  CAS  PubMed  Google Scholar 

  26. Noori-Daloii, M.-R., et al. (2012). Use of siRNA in knocking down of dopamine receptors, a possible therapeutic option in neuropsychiatric disorders Molecular. Biology Reports, 39, 2003–2010. https://doi.org/10.1007/s11033-011-0947-3

    Article  CAS  Google Scholar 

  27. Jetten, N., et al. (2014). Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses. PLoS ONE, 9, e102994.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Lauer, A., et al. (2020). Biofabrication of SDF-1 functionalized 3D-printed cell-free scaffolds for bone tissue regeneration. International Journal of Molecular Sciences, 21, 2175.

    Article  CAS  PubMed Central  Google Scholar 

  29. Anzai, A., et al. (2012). Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. Circulation, 125, 1234–1245.

    Article  PubMed  Google Scholar 

  30. Julier, Z., Park, A. J., Briquez, P. S., & Martino, M. M. (2017). Promoting tissue regeneration by modulating the immune system. Acta Biomaterialia, 53, 13–28.

    Article  CAS  PubMed  Google Scholar 

  31. Liu, G., Ma, H., Qiu, L., Li, L., Cao, Y., Ma, J., & Zhao, Y. (2011). Phenotypic and functional switch of macrophages induced by regulatory CD4+ CD25+ T cells in mice. Immunology and Cell Biology, 89, 130–142.

    Article  CAS  PubMed  Google Scholar 

  32. Lei, H., Schmidt-Bleek, K., Dienelt, A., Reinke, P., & Volk, H.-D. (2015). Regulatory T cell-mediated anti-inflammatory effects promote successful tissue repair in both indirect and direct manners. Frontiers in Pharmacology, 6, 184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nosbaum, A., et al. (2016). Cutting edge: Regulatory T cells facilitate cutaneous wound healing. The Journal of Immunology, 196, 2010–2014.

    Article  CAS  PubMed  Google Scholar 

  34. Aggarwal, N. R., et al. (2010). Regulatory T cell-mediated resolution of lung injury: Identification of potential target genes via expression profiling. Physiological Genomics, 41, 109–119.

    Article  CAS  PubMed  Google Scholar 

  35. Garibaldi, B. T., et al. (2013). Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment American. Journal of Respiratory Cell and Molecular Biology, 48, 35–43. https://doi.org/10.1165/rcmb.2012-0198OC

    Article  CAS  Google Scholar 

  36. Trujillo, G., Hartigan, A. J., & Hogaboam, C. M. (2010). T regulatory cells and attenuated bleomycin-induced fibrosis in lungs of CCR7-/-mice. Fibrogenesis & Tissue Repair, 3, 18.

    Article  CAS  Google Scholar 

  37. Gandolfo, M. T., et al. (2010). Mycophenolate mofetil modifies kidney tubular injury and Foxp3+ regulatory T cell trafficking during recovery from experimental ischemia–reperfusion. Transplant Immunology, 23, 45–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lai, L.-W., Yong, K.-C., & Lien, Y.-H.H. (2012). Pharmacologic recruitment of regulatory T cells as a therapy for ischemic acute kidney injury. Kidney International, 81, 983–992.

    Article  CAS  PubMed  Google Scholar 

  39. Rigamonti, E., Zordan, P., Sciorati, C., Rovere-Querini, P., & Brunelli, S. (2014). Macrophage plasticity in skeletal muscle repair. BioMed Research International, 2014, 1–9.

    Article  Google Scholar 

  40. Meng, X., et al. (2016). Regulatory T cells in cardiovascular diseases. Nature Reviews Cardiology, 13, 167–179.

    Article  CAS  PubMed  Google Scholar 

  41. Ramirez, K., Witherden, D. A., & Havran, W. L. (2015). All hands on DE (T) C: Epithelial-resident γδ T cells respond to tissue injury. Cellular Immunology, 296, 57–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ono, T., Okamoto, K., Nakashima, T., Nitta, T., Hori, S., Iwakura, Y., & Takayanagi, H. (2016). IL-17-producing γδ T cells enhance bone regeneration. Nature Communications, 7, 1–9.

    Article  Google Scholar 

  43. Kumar, P., Rajasekaran, K., Palmer, J. M., Thakar, M. S., & Malarkannan, S. (2013). IL-22: An evolutionary missing-link authenticating the role of the immune system in tissue regeneration. Journal of Cancer, 4, 57.

    Article  CAS  PubMed  Google Scholar 

  44. Liu, Y., et al. (2011). Mesenchymal stem cell–based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nature Medicine, 17, 1594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Reinke, S., et al. (2013). Terminally differentiated CD8+ T cells negatively affect bone regeneration in humans. Science Translational Medicine, 5, 177.

    Article  CAS  Google Scholar 

  46. Tang, Y., Zhang, M. J., Hellmann, J., Kosuri, M., Bhatnagar, A., & Spite, M. (2013). Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes, 62, 618–627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vasconcelos, D. P., Costa, M., Amaral, I. F., Barbosa, M. A., Águas, A. P., & Barbosa, J. N. (2015). Development of an immunomodulatory biomaterial: Using resolvin D1 to modulate inflammation. Biomaterials, 53, 566–573.

    Article  CAS  PubMed  Google Scholar 

  48. Vasconcelos, D. P., et al. (2018). Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing. Journal of Biomedical Materials Research Part A, 106, 1626–1633.

    Article  CAS  PubMed  Google Scholar 

  49. Shi, J., et al. (2019). Regulation of the inflammatory response by vascular grafts modified with aspirin-triggered resolvin D1 promotes blood vessel regeneration. Acta Biomaterialia, 97, 360–373.

    Article  CAS  PubMed  Google Scholar 

  50. Chen, W. C. W., et al. (2015). Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair. Biomaterials, 72, 138–151. https://doi.org/10.1016/j.biomaterials.2015.08.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. King, A., Balaji, S., Le, L. D., Crombleholme, T. M., & Keswani, S. G. (2014). Regenerative wound healing: The role of interleukin-10. Advances in Wound Care, 3, 315–323.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Celik, M. Ö., Labuz, D., Keye, J., Glauben, R., & Machelska, H. (2020). IL-4 induces M2 macrophages to produce sustained analgesia via opioids. JCI Insight, 5, e133093. https://doi.org/10.1172/jci.insight.133093

    Article  PubMed Central  Google Scholar 

  53. Noori-daloii, M. R., et al. (2015). Knocking down the DRD2 by shRNA expressing plasmids in the nucleus accumbens prevented the disrupting effect of apomorphine on prepulse inhibition in rat. Journal of Sciences, Islamic Republic of Iran, 26, 205–212.

    Google Scholar 

  54. Shukla, G. S., & Chandra, S. (1987). Concurrent exposure to lead, manganese, and cadmium and their distribution to various brain regions, liver, kidney, and testis of growing rats. Archives of Environmental Contamination and Toxicology, 16, 303–310.

    Article  CAS  PubMed  Google Scholar 

  55. Spiller, K. L., Anfang, R. R., Spiller, K. J., Ng, J., Nakazawa, K. R., Daulton, J. W., & Vunjak-Novakovic, G. (2014). The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials, 35, 4477–4488. https://doi.org/10.1016/j.biomaterials.2014.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kuipers, S., Boin, A., Bossong, R., & Hegemann, H. (2015). Building joint crisis management capacity? Comparing civil security systems in 22 European countries. Risk, Hazards & Crisis in Public Policy, 6, 1–21.

    Article  Google Scholar 

  57. Penn, J. W., Grobbelaar, A. O., & Rolfe, K. J. (2012). The role of the TGF-β family in wound healing, burns and scarring: A review. International Journal of Burns and Trauma, 2, 18–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Gonçalves, J. F., et al. (2010). N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chemico-Biological Interactions, 186, 53–60.

    Article  PubMed  CAS  Google Scholar 

  59. Snutch, T. P., Peloquin, J., Mathews, E., McRory, J. E. (2013). Molecular properties of voltage-gated calcium channels. In: Madame Curie Bioscience Database [Internet]. Landes Bioscience

  60. Barnham, K. J., & Bush, A. I. (2008). Metals in Alzheimer’s and Parkinson’s diseases. Current Opinion in Chemical Biology, 12, 222–228.

    Article  CAS  PubMed  Google Scholar 

  61. Polson, A. K., Sokol, M. B., Dineley, K. E., & Malaiyandi, L. M. (2011). Matrix cadmium accumulation depolarizes mitochondria isolated from mouse brain. Impulse, 2011, 1–8.

    Google Scholar 

  62. El-Tarras, A.E.-S., Attia, H. F., Soliman, M. M., El Awady, M. A., & Amin, A. A. (2016). Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats. International Journal of Immunopathology and Pharmacology, 29, 398–407.

    Article  PubMed Central  Google Scholar 

  63. García, J. R., Quirós, M., Han, W. M., O’Leary, M. N., Cox, G. N., Nusrat, A., & García, A. J. (2019). IFN-γ-tethered hydrogels enhance mesenchymal stem cell-based immunomodulation and promote tissue repair. Biomaterials, 220, 119403. https://doi.org/10.1016/j.biomaterials.2019.119403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bujak, M., Dobaczewski, M., Chatila, K., Mendoza, L. H., Li, N., Reddy, A., & Frangogiannis, N. G. (2008). Interleukin-1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. The American Journal of Pathology, 173, 57–67.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Suzuki, K., Murtuza, B., Smolenski, R. T., Sammut, I. A., Suzuki, N., Kaneda, Y., & Yacoub, M. H. (2001). Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injury associated with reduction in apoptosis. Circulation, 104, 308–313.

    Article  Google Scholar 

  66. Turner, N. A., Warburton, P., O’Regan, D. J., Ball, S. G., & Porter, K. E. (2010). Modulatory effect of interleukin-1α on expression of structural matrix proteins, MMPs and TIMPs in human cardiac myofibroblasts: Role of p38 MAP kinase. Matrix Biology, 29, 613–620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Frangogiannis, N. G. (2015). Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries, 3, e41.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Hwang, M.-W., et al. (2001). Neutralization of interleukin-1β in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. Journal of the American College of Cardiology, 38, 1546–1553.

    Article  CAS  PubMed  Google Scholar 

  69. Granados-Romero, J. J., et al. (2017). Colorectal cancer: A review. International Journal of Research in Medical Science, 5, 4667–4676.

    Article  Google Scholar 

  70. Mountziaris, P. M., & Mikos, A. G. (2008). Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Engineering Part B: Reviews, 14, 179–186.

    Article  CAS  Google Scholar 

  71. Bartosh, T. J., et al. (2010). Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proceedings of the National Academy of Sciences USA, 107, 13724–13729.

    Article  CAS  Google Scholar 

  72. Ren, G., et al. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2, 141–150.

    Article  CAS  PubMed  Google Scholar 

  73. Roddy, G. W., et al. (2011). Action at a distance: Systemically administered adult stem/progenitor cells (MSCs) reduce inflammatory damage to the cornea without engraftment and primarily by secretion of TNF-α stimulated gene/protein 6. Stem Cells, 29, 1572–1579.

    Article  CAS  PubMed  Google Scholar 

  74. Aktas, E., et al. (2017). Immune modulation with primed mesenchymal stem cells delivered via biodegradable scaffold to repair an Achilles tendon segmental defect. Journal of Orthopaedic Research, 35, 269–280.

    Article  CAS  PubMed  Google Scholar 

  75. de Oliveira Carvalho, P. E., Magolbo, N. G., De Aquino, R. F., & Weller, C. D. (2016). Oral aspirin for treating venous leg ulcers. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD009432.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  76. Cantón, I., Mckean, R., Charnley, M., Blackwood, K. A., Fiorica, C., Ryan, A. J., & MacNeil, S. (2010). Development of an Ibuprofen-releasing biodegradable PLA/PGA electrospun scaffold for tissue regeneration. Biotechnology and Bioengineering, 105, 396–408.

    Article  PubMed  CAS  Google Scholar 

  77. Varatharajan, L., Thapar, A., Lane, T., Munster, A. B., & Davies, A. H. (2016). Pharmacological adjuncts for chronic venous ulcer healing: A systematic review. Phlebology, 31, 356–365. https://doi.org/10.1177/0268355515587194

    Article  PubMed  Google Scholar 

  78. Friedrich, E. E., Sun, L. T., Natesan, S., Zamora, D. O., Christy, R. J., & Washburn, N. R. (2014). Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns. Journal of Biomedical Materials Research Part A, 102, 1527–1536. https://doi.org/10.1002/jbm.a.34829

    Article  CAS  PubMed  Google Scholar 

  79. Asea, A., et al. (2002). Novel signal transduction pathway utilized by extracellular HSP70: Role of toll-like receptor (TLR) 2 and TLR4. The Journal of Biological Chemistry, 277, 15028–15034. https://doi.org/10.1074/jbc.M200497200

    Article  CAS  PubMed  Google Scholar 

  80. Kovalchin, P., Joseph, T., Wang, M., PhD, R., Wagh, M., Mihir, S., Azoulay, B., Jason, S. M., & Melinda, C. R. Y. (2006). In vivo delivery of heat shock protein 70 accelerates wound healing by up-regulating macrophage-mediated phagocytosis. Wound Repair and Regeneration, 14, 129–137. https://doi.org/10.1111/j.1743-6109.2006.00102.x

    Article  PubMed  Google Scholar 

  81. Yamamoto, M., Sato, T., Beren, J., Verthelyi, D., & Klinman, D. M. (2011). The acceleration of wound healing in primates by the local administration of immunostimulatory CpG oligonucleotides. Biomaterials, 32, 4238–4242. https://doi.org/10.1016/j.biomaterials.2011.02.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chen, P., et al. (2015). Radially oriented collagen scaffold with SDF-1 promotes osteochondral repair by facilitating cell homing. Biomaterials, 39, 114–123. https://doi.org/10.1016/j.biomaterials.2014.10.049

    Article  CAS  PubMed  Google Scholar 

  83. Theiss, H. D., et al. (2011). Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis. Stem Cell Research, 7, 244–255. https://doi.org/10.1016/j.scr.2011.05.003

    Article  CAS  PubMed  Google Scholar 

  84. Bajetto, A., et al. (2006). Expression of CXC chemokine receptors 1–5 and their ligands in human glioma tissues: Role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochemistry International, 49, 423–432. https://doi.org/10.1016/j.neuint.2006.03.003

    Article  CAS  PubMed  Google Scholar 

  85. Kimura, Y., & Tabata, Y. (2010). Controlled release of stromal-cell-derived factor-1 from gelatin hydrogels enhances angiogenesis. Journal of Biomaterials Science, Polymer Edition, 21, 37–51. https://doi.org/10.1163/156856209X410193

    Article  CAS  Google Scholar 

  86. Rabbany, S. Y., Pastore, J., Yamamoto, M., Miller, T., Rafii, S., Aras, R., & Penn, M. (2010). Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing. Cell Transplantation, 19, 399–408. https://doi.org/10.3727/096368909x481782

    Article  PubMed  Google Scholar 

  87. Zhang, G. E., Nakamura, Y., Wang, X., Hu, Q., Suggs, L. J., & Zhang, J. (2004). Controlled release of stromal cell-derived factor-1alpha in situ increases C-kit+ cell homing to the infarcted heart. Tissue Engineering, 13, 2063–2071. https://doi.org/10.1089/ten.2006.0013

    Article  Google Scholar 

  88. Thevenot, P. T., Nair, A. M., Shen, J., Lotfi, P., Ko, C.-Y., & Tang, L. (2010). The effect of incorporation of SDF-1α into PLGA scaffolds on stem cell recruitment and the inflammatory response. Biomaterials, 31, 3997–4008. https://doi.org/10.1016/j.biomaterials.2010.01.144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Shen, W., Chen, X., Chen, J., Yin, Z., Heng, B. C., Chen, W., & Ouyang, H.-W. (2010). The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. Biomaterials, 31, 7239–7249. https://doi.org/10.1016/j.biomaterials.2010.05.040

    Article  CAS  PubMed  Google Scholar 

  90. Projahn, D., et al. (2014). Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction. Journal of Cellular and Molecular Medicine, 18, 790–800. https://doi.org/10.1111/jcmm.12225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lau, T. T., & Wang, D.-A. (2011). Stromal cell-derived factor-1 (SDF-1): Homing factor for engineered regenerative medicine. Expert Opinion on Biological Therapy, 11, 189–197. https://doi.org/10.1517/14712598.2011.546338

    Article  CAS  PubMed  Google Scholar 

  92. Xu, M., Wei, X., Fang, J., & Xiao, L. (2019). Combination of SDF-1 and bFGF promotes bone marrow stem cell-mediated periodontal ligament regeneration. Bioscience Reports, 39, BSR20190785. https://doi.org/10.1042/BSR20190785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Armulik, A., Genové, G., & Betsholtz, C. (2011). Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises. Developmental Cell, 21, 193–215. https://doi.org/10.1016/j.devcel.2011.07.001

    Article  CAS  PubMed  Google Scholar 

  94. Noguchi, K., & Ishikawa, I. (2007). The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontology, 43, 85–101. https://doi.org/10.1111/j.1600-0757.2006.00170.x

    Article  Google Scholar 

  95. Paralkar, V. M., et al. (2003). An EP2 receptor-selective prostaglandin E2 agonist induces bone healing. Proceedings of the National Academy of Sciences USA, 100, 6736–6740. https://doi.org/10.1073/pnas.1037343100

    Article  CAS  Google Scholar 

  96. Namkoong, S., et al. (2005). Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells. Experimental & Molecular Medicine, 37, 588–600. https://doi.org/10.1038/emm.2005.72

    Article  CAS  Google Scholar 

  97. Kato, N., et al. (2007). Nanogel-based delivery system enhances PGE2 effects on bone formation. Journal of Cellular Biochemistry, 101, 1063–1070. https://doi.org/10.1002/jcb.21160

    Article  CAS  PubMed  Google Scholar 

  98. Toyoda, H., Terai, H., Sasaoka, R., Oda, K., & Takaoka, K. (2005). Augmentation of bone morphogenetic protein-induced bone mass by local delivery of a prostaglandin E EP4 receptor agonist. Bone, 37, 555–562. https://doi.org/10.1016/j.bone.2005.04.042

    Article  CAS  PubMed  Google Scholar 

  99. Leng, Q., Chen, L., & Lv, Y. (2020). RNA-based scaffolds for bone regeneration: Application and mechanisms of mRNA, miRNA and siRNA. Theranostics, 10, 3190–3205. https://doi.org/10.7150/thno.42640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Haber, B. A., Mohn, K. L., Diamond, R. H., & Taub, R. (1993). Induction patterns of 70 genes during nine days after hepatectomy define the temporal course of liver regeneration. The Journal of Clinical Investigation, 91, 1319–1326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Li, W., Liang, X., Leu, J. I., Kovalovich, K., Ciliberto, G., & Taub, R. (2001). Global changes in interleukin-6–dependent gene expression patterns in mouse livers after partial hepatectomy. Hepatology, 33, 1377–1386. https://doi.org/10.1053/jhep.2001.24431

    Article  CAS  PubMed  Google Scholar 

  102. Cressman, D. E., Diamond, R. H., & Taub, R. (1995). Rapid activation of the Stat3 transcription complex in liver regeneration. Hepatology, 21, 1443–1449.

    Article  CAS  PubMed  Google Scholar 

  103. FitzGerald, M., Webber, E., Donovan, J., & Fausto, N. (1995). Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration. Cell Growth & Differentiation, 6, 417–427.

    CAS  Google Scholar 

  104. Taub, R. (2004). Liver regeneration: From myth to mechanism Nature reviews. Molecular Cell Biology, 5, 836–847.

    CAS  PubMed  Google Scholar 

  105. Campbell, J. S., et al. (2001). Expression of suppressors of cytokine signaling during liver regeneration. The Journal of Clinical Investigation, 107, 1285–1292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wüstefeld, T., Rakemann, T., Kubicka, S., Manns, M. P., & Trautwein, C. (2000). Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice. Hepatology, 32, 514–522.

    Article  PubMed  Google Scholar 

  107. Manibur Rahman, T. (2000). Animal models of acute hepatic failure. International Journal of Experimental Pathology, 81, 145–157.

    Article  PubMed  Google Scholar 

  108. Chen, Z., Klein, T., Murray, R. Z., Crawford, R., Chang, J., Wu, C., & Xiao, Y. (2016). Osteoimmunomodulation for the development of advanced bone biomaterials. Materials Today, 19, 304–321.

    Article  CAS  Google Scholar 

  109. Michalski, M. N., & McCauley, L. K. (2017). Macrophages and skeletal health. Pharmacology & Therapeutics, 174, 43–54.

    Article  CAS  Google Scholar 

  110. Sinder, B. P., Pettit, A. R., & McCauley, L. K. (2015). Macrophages: Their emerging roles in bone. Journal of Bone and Mineral Research, 30, 2140–2149.

    Article  PubMed  Google Scholar 

  111. Heinemann, D., Lohmann, C., Siggelkow, H., Alves, F., Engel, I., & Köster, G. (2000). Human osteoblast-like cells phagocytose metal particles and express the macrophage marker CD68 in vitro. The Journal of Bone and Joint Surgery British, 82, 283–289.

    Article  CAS  Google Scholar 

  112. Kikuchi, T., et al. (2001). Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors. The Journal of Immunology, 166, 3574–3579.

    Article  CAS  PubMed  Google Scholar 

  113. Reyes-Botella, C., Montes, M., Vallecillo-Capilla, M., Olivares, E., & Ruiz, C. (2000). Expression of molecules involved in antigen presentation and T cell activation (HLA-DR, CD80, CD86, CD44 and CD54) by cultured human osteoblasts. Journal of Periodontology, 71, 614–617.

    Article  CAS  PubMed  Google Scholar 

  114. Tobin, S. W., Alibhai, F. J., Weisel, R. D., & Li, R.-K. (2020). Considering cause and effect of immune cell aging on cardiac repair after myocardial infarction. Cells, 9, 1894.

    Article  CAS  PubMed Central  Google Scholar 

  115. Zouggari, Y., et al. (2013). B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nature Medicine, 19, 1273–1280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Nahrendorf, M., et al. (2007). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. The Journal of Experimental Medicine, 204, 3037–3047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Nahrendorf, M., et al. (2007). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. Journal of Experimental Medicine, 204, 3037–3047. https://doi.org/10.1084/jem.20070885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Felger, J. C., et al. (2010). Brain dendritic cells in ischemic stroke: Time course, activation state, and origin. Brain, Behavior, and Immunity, 24, 724–737.

    Article  CAS  PubMed  Google Scholar 

  119. Iadecola, C., & Anrather, J. (2011). The immunology of stroke: From mechanisms to translation. Nature Medicine, 17, 796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Miron, V. E., et al. (2013). M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nature Neuroscience, 16, 1211–1218. https://doi.org/10.1038/nn.3469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sas, A. R., et al. (2020). A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nature immunology, 21, 1496–1505.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

This study was part of the Ph.D. dissertation supported by the Tehran University of Medical Sciences (Grant No: 98-01-30-41244). The authors would like to acknowledge the Iran National Science Foundation (INSF, Grant No: 98001385) and also, Council for Development of Stem cell Sciences and Technologies (Grant No: 11/35723).

Author information

Authors and Affiliations

  1. Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Masoomeh Masoomikarimi

  2. Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

  3. Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

  4. Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Majid Salehi

Authors
  1. Masoomeh Masoomikarimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Majid Salehi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Majid Salehi.

Ethics declarations

Conflict of interest

The authors have no financial conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Masoomikarimi, M., Salehi, M. Modulation of the Immune System Promotes Tissue Regeneration. Mol Biotechnol 64, 599–610 (2022). https://doi.org/10.1007/s12033-021-00430-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-021-00430-8

Keywords

Search

Navigation