Advertisement

Stem Cell Reviews and Reports

, Volume 10, Issue 4, pp 587–599 | Cite as

Mesenchymal Stem Cell Priming: Fine-tuning Adhesion and Function

  • Dean P. J. Kavanagh
  • Joseph Robinson
  • Neena Kalia
Article

Abstract

There is significant interest in the use of mesenchymal stem cells (MSCs) as a potential therapeutic modality in disease and disorder, particularly those with an inflammation-based component such as coronary, renal and hepatic diseases. While there is no question that MSCs possess the capability to manipulate an ongoing inflammatory injury, the recruitment of these cells to injured sites is generally poor, and thus, open to manipulation. Enhancing the localised recruitment of MSCs to injured tissues may enhance the efficiency and efficacy of this mode of therapy. A number of techniques exist in the literature to improve the recruitment of MSCs to injured tissues, including the use of cytokines, chemical modifications and coating with either synthetic or biological particles. In addition to enhancing MSC recruitment, there is an increasing body of work examining techniques which may enhance the anti-inflammatory activity of these cells. This review will summarise the literature around these topics. This first section of this review summarises the current literature with regard to MSC homing and their recruitment during conditions of injury. In relation to the anti-inflammatory activity of MSCs, the role of systemic versus local activity will be discussed. The second part of the review focuses on the role of pretreatments in MSC therapy and how these may have potential for not only enhancing the recruitment of MSCs, but also their anti-inflammatory capabilities. In summary, it is clear that there is significant potential to improve the efficiency of MSC therapy and the techniques discussed in this review may be central to this in the future.

Keywords

Cell adhesion Cell recruitment Mesenchymal stem cells Cytokines Cytotherapy Stem cells Cell therapy 

Notes

Acknowledgments

The authors would like to thank Dr Craig Hughes for critical reading of the manuscript.

Disclosures

The authors indicate no potential conflicts of interest.

References

  1. 1.
    Dominici, M., et al. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement. Cytotherapy, 8(4), 315–7.PubMedGoogle Scholar
  2. 2.
    Sohn, R., & Gussoni, E. (2004). Stem cell therapy for muscular dystrophy. Expert Opinion on Biological Therapy, 4(1), 1–9.PubMedGoogle Scholar
  3. 3.
    Fiorina, P., et al. (2009). Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type one diabetes. The Journal of Immunology, 183(2), 993–1004.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Silva, G. V., et al. (2005). Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation, 111(2), 150–156.PubMedGoogle Scholar
  5. 5.
    Friedenstein, A. J., et al. (1974). Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. cloning in vitro and retransplantation in vivo. Transplantation, 17(4), 331–40.PubMedGoogle Scholar
  6. 6.
    Caplan, A. I. (1991). Mesenchymal stem cells. Journal of Orthopaedic Research, 9(5), 641–50.PubMedGoogle Scholar
  7. 7.
    Lanza, R.P., Gearhart, J., Hogan, B. (2006). Essentials of stem cell biology. illustrated, abridged ed. (p206). Academic PressGoogle Scholar
  8. 8.
    Kohyama, J., et al. (2001). Brain from bone: efficient “meta-differentiation” of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent. Differentiation, 68(4–5), 235–44.PubMedGoogle Scholar
  9. 9.
    Malgieri, A., et al. (2010). Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. International Journal of Clinical and Experimental Medicine, 3(4), 248–69.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Cao, H., et al. (2010). Mesenchymal stem cells derived from human umbilical cord ameliorate ischemia/reperfusion-induced acute renal failure in rats. Biotechnology Letters, 32(5), 725–732.PubMedGoogle Scholar
  11. 11.
    Summer, R., et al. (2007). Isolation of an adult mouse lung mesenchymal progenitor cell population. American Journal of Respiratory Cell and Molecular Biology, 37(2), 152–9.PubMedCentralPubMedGoogle Scholar
  12. 12.
    Huang, Y., et al. (2009). Kidney-derived stromal cells modulate dendritic and T cell responses. Journal of the American Society of Nephrology, 20(4), 831–41.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Zuk, P. A., et al. (2002). Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, 13(12), 4279–4295.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Tomar, G. B., et al. (2010). Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochemical and Biophysical Research Communications, 393(3), 377–83.PubMedGoogle Scholar
  15. 15.
    Houlihan, D. D., et al. (2012). Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-alpha. Nature Protocols, 7(12), 2103–11.PubMedGoogle Scholar
  16. 16.
    Krampera, M., et al. (2013). Immunological characterization of multipotent mesenchymal stromal cells-The International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy, 15(9), 1054–1061.Google Scholar
  17. 17.
    Peister, A., et al. (2004). Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood, 103(5), 1662–8.PubMedGoogle Scholar
  18. 18.
    Morikawa, S., et al. (2009). Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. Journal of Experimental Medicine, 206(11), 2483–96.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Ren, G., et al. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2(2), 141–50.PubMedGoogle Scholar
  20. 20.
    Ren, G., et al. (2009). Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells, 27(8), 1954–62.PubMedGoogle Scholar
  21. 21.
    Le Blanc, K., et al. (2003). HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Experimental Hematology, 31(10), 890–6.PubMedGoogle Scholar
  22. 22.
    Griffin, M. D., et al. (2013). Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far? Immunology and Cell Biology, 91(1), 40–51.PubMedGoogle Scholar
  23. 23.
    Camp, D. M., et al. (2009). Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease. Journal of Neuroinflammation, 6, 17.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Huang, X. P., et al. (2010). Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation, 122(23), 2419–29.PubMedGoogle Scholar
  25. 25.
    Isakova, I. A., et al. (2010). Cell-dose-dependent increases in circulating levels of immune effector cells in rhesus macaques following intracranial injection of allogeneic MSCs. Experimental Hematology, 38(10), 957–967.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Eliopoulos, N., et al. (2005). Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood, 106(13), 4057–65.PubMedGoogle Scholar
  27. 27.
    Seifert, M., et al. (2012). Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection. Frontiers in Immunology, 3, 202.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Schu, S., et al. (2012). Immunogenicity of allogeneic mesenchymal stem cells. Journal of Cellular and Molecular Medicine, 16(9), 2094–103.PubMedGoogle Scholar
  29. 29.
    Liotta, F., et al. (2008). Toll-like receptors three and four are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells, 26(1), 279–89.PubMedGoogle Scholar
  30. 30.
    Augello, A., et al. (2005). Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death one pathway. European Journal of Immunology, 35(5), 1482–90.PubMedGoogle Scholar
  31. 31.
    Gonzalez-Rey, E., et al. (2009). Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut, 58(7), 929–939.PubMedGoogle Scholar
  32. 32.
    Togel, F., et al. (2005). Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury. Kidney International, 67(5), 1772–84.PubMedGoogle Scholar
  33. 33.
    Suga, H., et al. (2009). IFATS collection: Fibroblast growth factor-two-induced hepatocyte growth factor secretion by adipose-derived stromal cells inhibits postinjury fibrogenesis through a c-Jun N-terminal kinase-dependent mechanism. Stem Cells, 27(1), 238–49.PubMedGoogle Scholar
  34. 34.
    Hou, X., et al. (2010). Erythropoietin augments the efficacy of therapeutic angiogenesis induced by allogenic bone marrow stromal cells in a rat model of limb ischemia. Molecular Biology Reports, 37(3), 1467–75.PubMedGoogle Scholar
  35. 35.
    Rehman, J., et al. (2004). Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation, 109(10), 1292–8.PubMedGoogle Scholar
  36. 36.
    Hung, S. C., et al. (2007). Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells, 25(9), 2363–70.PubMedGoogle Scholar
  37. 37.
    Choi, H., et al. (2011). Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. Blood, 118(2), 330–8.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Walenda, T., et al. (2011). Synergistic effects of growth factors and mesenchymal stromal cells for expansion of hematopoietic stem and progenitor cells. Experimental Hematology, 39(6), 617–28.PubMedGoogle Scholar
  39. 39.
    Nemeth, K., et al. (2009). Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-ten production. Nature Medicine, 15(1), 42–49.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Shah, K. (2012). Mesenchymal stem cells engineered for cancer therapy. Advanced Drug Delivery Reviews, 64(8), 739–48.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Dai, T., et al. (2013). Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system. International Journal Pharmaceutics, 456(1),186–194.Google Scholar
  42. 42.
    Cavarretta, I. T., et al. (2010). Adipose tissue-derived mesenchymal stem cells expressing prodrug-converting enzyme inhibit human prostate tumor growth. Molecular Therapy, 18(1), 223–31.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Chen, T. S., et al. (2011). Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. Journal of Translational Medicine, 9, 47.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Yeo, R. W., et al. (2013). Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Advanced Drug Delivery Reviews, 65(3), 336–41.PubMedGoogle Scholar
  45. 45.
    van Dommelen, S. M., et al. (2012). Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery. Journal of Controlled Release, 161(2), 635–644.PubMedGoogle Scholar
  46. 46.
    Mohit, E., & Rafati, S. (2013). Biological delivery approaches for gene therapy: strategies to potentiate efficacy and enhance specificity. Molecular Immunology, 56(4), 599–611.PubMedGoogle Scholar
  47. 47.
    Chapel, A., et al. (2003). Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome. The Journal of Gene Medicine, 5(12), 1028–1038.PubMedGoogle Scholar
  48. 48.
    Ortiz, L. A., et al. (2003). Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proceedings of the National Academy of Sciences, 100(14), 8407–8411.Google Scholar
  49. 49.
    Chang, P., et al. (2013). Multi-therapeutic effects of human adipose-derived mesenchymal stem cells on radiation-induced intestinal injury. Cell Death and Disease, 4, e685.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Aldridge, V., et al. (2012). Human mesenchymal stem cells are recruited to injured liver in a β1-integrin and CD44 dependent manner. Hepatology, 56(3), 1063–1073.PubMedGoogle Scholar
  51. 51.
    Eggenhofer, E., et al. (2012). Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Frontiers Immunology, 3, 297.Google Scholar
  52. 52.
    Ramirez, M., et al. (2006). Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury. British Journal of Sports Medicine, 40(8), 719–22.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Rochefort, G. Y., et al. (2006). Multipotential mesenchymal stem cells are mobilized into peripheral blood by hypoxia. Stem Cells, 24(10), 2202–8.PubMedGoogle Scholar
  54. 54.
    Wang, Y., et al. (2006). Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart, 92(6), 768–74.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Wang, N., et al. (2012). Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6. PLoS ONE, 7(8), e43768.PubMedCentralPubMedGoogle Scholar
  56. 56.
    Lee, R. H., et al. (2009). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell, 5(1), 54–63.PubMedGoogle Scholar
  57. 57.
    Danchuk, S., et al. (2011). Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-alpha-induced protein 6. Stem Cell Research Therapy, 2(3), 27.PubMedCentralPubMedGoogle Scholar
  58. 58.
    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 six. Stem Cells, 29(10), 1572–1579.PubMedGoogle Scholar
  59. 59.
    Scruggs, B. A., et al. (2013). Multipotent stromal cells alleviate inflammation, neuropathology, and symptoms associated with globoid cell leukodystrophy in the twitcher mouse. Stem Cells, 31(8), 1523–34.PubMedCentralPubMedGoogle Scholar
  60. 60.
    Moghimi, S. M., Hunter, A. C., & Murray, J. C. (2001). Long-circulating and target-specific nanoparticles: theory to practice. Pharmacological Reviews, 53(2), 283–318.PubMedGoogle Scholar
  61. 61.
    Schrepfer, S., et al. (2007). Stem cell transplantation: the lung barrier. Transplantation Proceedings, 39(2), 573–6.PubMedGoogle Scholar
  62. 62.
    Chamberlain, G., et al. (2007). Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 25(11), 2739–49.PubMedGoogle Scholar
  63. 63.
    Majumdar, M. K., et al. (2003). Characterization and functionality of cell surface molecules on human mesenchymal stem cells. Journal of Biomedical Science, 10, 228–241.PubMedGoogle Scholar
  64. 64.
    Lo Surdo, J., & Bauer, S. R. (2012). Quantitative approaches to detect donor and passage differences in adipogenic potential and clonogenicity in human bone marrow-derived mesenchymal stem cells. Tissue Engineering. Part C, Methods, 18(11), 877–89.PubMedCentralPubMedGoogle Scholar
  65. 65.
    De Ugarte, D. A., et al. (2003). Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunology Letters, 89(2–3), 267–70.PubMedGoogle Scholar
  66. 66.
    Pevsner-Fischer, M., Levin, S., & Zipori, D. (2011). The origins of mesenchymal stromal cell heterogeneity. Stem Cell Reviews, 7(3), 560–8.PubMedGoogle Scholar
  67. 67.
    Rüster, B., et al. (2006). Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood, 108, 3938–3944.PubMedGoogle Scholar
  68. 68.
    Aziz, K. A., et al. (2000). Involvement of CD44-hyaluronan interaction in malignant cell homing and fibronectin synthesis in hairy cell leukemia. Blood, 96(9), 3161–3167.PubMedGoogle Scholar
  69. 69.
    Alves, C. S., et al. (2008). The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion. American Journal of Physiology - Cell Physiolog, 294(4), C907–C916.Google Scholar
  70. 70.
    Dimitroff, C. J., et al. (2000). A distinct glycoform of CD44 is an L-selectin ligand on human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America, 97(25), 13841–6.PubMedCentralPubMedGoogle Scholar
  71. 71.
    Burdick, M. M., et al. (2006). HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells. Journal of Biological Chemistry, 281(20), 13899–13905.PubMedGoogle Scholar
  72. 72.
    Avigdor, A., et al. (2004). CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood, 103(8), 2981–9.PubMedGoogle Scholar
  73. 73.
    Thankamony, S. P., & Sackstein, R. (2011). Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells. Proceedings of the National Academy of Sciences, 108(6), 2258–2263.Google Scholar
  74. 74.
    Ciuculescu, F., et al. (2011). Variability in chemokine-induced adhesion of human mesenchymal stromal cells. Cytotherapy, 13(10), 1172–9.PubMedGoogle Scholar
  75. 75.
    Herrera, M. B., et al. (2007). Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury. Kidney International, 72(4), 430–41.PubMedGoogle Scholar
  76. 76.
    Ip, J. E., et al. (2007). Mesenchymal stem cells use integrin beta1 not CXC chemokine receptor four for myocardial migration and engraftment. Molecular Biology of the Cell, 18, 2873–2882.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Schreiber, T.D., et al .(2009). The integrin {alpha} 9 {beta} 1 on hematopoietic stem and progenitor cells: involvement in cell adhesion, proliferation and differentiation. Haematologica, p. [epub ahead of print].Google Scholar
  78. 78.
    Langer, H. F., et al. (2009). Platelet derived bFGF mediates vascular integrative mechanisms of mesenchymal stem cells in vitro. Journal of Molecular and Cellular Cardiology, 47(2), 315–25.PubMedGoogle Scholar
  79. 79.
    Gao, J., et al. (2001). The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells, Tissues, Organs, 169(1), 12–20.PubMedGoogle Scholar
  80. 80.
    Shi, M., et al. (2007). Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice. Haematologica, 92(7), 897–904.PubMedGoogle Scholar
  81. 81.
    Bhakta, S., Hong, P., & Koc, O. (2006). The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovascular Revascularization Medicine, 7(1), 19–24.PubMedGoogle Scholar
  82. 82.
    Duijvestein, M., et al. (2011). Pretreatment with interferon-gamma enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis. Stem Cells, 29(10), 1549–58.PubMedGoogle Scholar
  83. 83.
    Kavanagh, D. P. J., & Kalia, N. (2011). Hematopoietic stem cell homing to injured tissues. Stem Cell Reviews and Reports, 7(3), 672–682.PubMedGoogle Scholar
  84. 84.
    Fan, H., et al. (2012). Pre-treatment with IL-1beta enhances the efficacy of MSC transplantation in DSS-induced colitis. Cellular and molecular immunology, 9(6), 473–81.PubMedGoogle Scholar
  85. 85.
    Lalu, M. M., et al. (2012). safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS ONE, 7(10), e47559.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Wang, L., et al. (2013). IFN-γ and TNF-α synergistically induce mesenchymal stem cell impairment and tumorigenesis via NFκB signaling. Stem Cells, 31(7), 1383–1395.PubMedCentralPubMedGoogle Scholar
  87. 87.
    Ceradini, D. J., et al. (2004). Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Medicine, 10(8), 858–64.PubMedGoogle Scholar
  88. 88.
    Hu, X., et al. (2011). Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. American Journal of Physiology. Cell Physiology, 301(2), C362–72.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Rosova, I., et al. (2008). Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells, 26(8), 2173–82.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Wei, N., et al. (2013). Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice. Cell Transplantation, 22(6), 977–91.PubMedGoogle Scholar
  91. 91.
    Crowder, S. W., et al. (2013). Passage-dependent cancerous transformation of human mesenchymal stem cells under carcinogenic hypoxia. FASEB Journal, 27(7), 2788–98.PubMedCentralPubMedGoogle Scholar
  92. 92.
    Estrada, J. C., et al. (2012). Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death and Differentiation, 19(5), 743–755.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Sarkar, D., et al. (2010). Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting. Biomaterials, 31(19), 5266–74.PubMedCentralPubMedGoogle Scholar
  94. 94.
    Sarkar, D., et al. (2008). Chemical engineering of mesenchymal stem cells to induce a cell rolling response. Bioconjugate Chemistry, 19(11), 2105–9.PubMedGoogle Scholar
  95. 95.
    Sarkar, D., et al. (2011). Engineered cell homing. Blood, 118(25), e184–91.PubMedCentralPubMedGoogle Scholar
  96. 96.
    Sackstein, R., et al. (2008). Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nature Medicine, 14(2), 181–7.PubMedGoogle Scholar
  97. 97.
    Huang, J., et al. (2010). Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circulation Research, 106(11), 1753–62.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Gheisari, Y., et al. (2012). Genetic modification of mesenchymal stem cells to overexpress CXCR4 and CXCR7 does not improve the homing and therapeutic potentials of these cells in experimental acute kidney injury. Stem Cells and Development, 21(16), 2969–80.PubMedGoogle Scholar
  99. 99.
    Cheng, Z., et al. (2008). Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Molecular Therapy, 16(3), 571–9.PubMedGoogle Scholar
  100. 100.
    Phillips, M. I., & Tang, Y. L. (2008). Genetic modification of stem cells for transplantation. Advanced Drug Delivery Reviews, 60(2), 160–172.PubMedCentralPubMedGoogle Scholar
  101. 101.
    Belay, E., et al. (2010). Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: a nonviral paradigm for coaxed differentiation. Stem Cells, 28(10), 1760–1771.PubMedGoogle Scholar
  102. 102.
    Zielske, S. P., Livant, D. L., & Lawrence, T. S. (2009). Radiation increases invasion of gene-modified mesenchymal stem cells into tumors. International Journal of Radiation Oncology, Biology, and Physics, 75(3), 843–53.Google Scholar
  103. 103.
    Klopp, A. H., et al. (2007). Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Research, 67(24), 11687–95.PubMedGoogle Scholar
  104. 104.
    Liang, X., et al. (2011). The low-dose ionizing radiation stimulates cell proliferation via activation of the MAPK/ERK pathway in rat cultured mesenchymal stem cells. Journal of Radiation Research, 52(3), 380–6.PubMedGoogle Scholar
  105. 105.
    Burks, S.R., et al. (2013). Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications. Stem Cells, 31(11), 2551–2560.Google Scholar
  106. 106.
    Ziadloo, A., et al. (2012). Enhanced homing permeability and retention of bone marrow stromal cells by noninvasive pulsed focused ultrasound. Stem Cells, 30(6), 1216–27.PubMedCentralPubMedGoogle Scholar
  107. 107.
    Ghanem, A., et al. (2009). Focused ultrasound-induced stimulation of microbubbles augments site-targeted engraftment of mesenchymal stem cells after acute myocardial infarction. Journal of Molecular and Cellular Cardiology, 47(3), 411–418.PubMedGoogle Scholar
  108. 108.
    Yanai, A., et al. (2012). Focused magnetic stem cell targeting to the retina using superparamagnetic iron oxide nanoparticles. Cell Transplantation, 21(6), 1137–48.PubMedGoogle Scholar
  109. 109.
    Landazuri, N., et al. (2013). Magnetic Targeting of Human Mesenchymal Stem Cells with Internalized Superparamagnetic Iron Oxide Nanoparticles. Small, 9(23), 4017–4026.Google Scholar
  110. 110.
    Waterman, R. S., et al. (2010). A new Mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 Phenotype. PLoS ONE, 5(4), e10088.PubMedCentralPubMedGoogle Scholar
  111. 111.
    Waterman, R. S., Henkle, S. L., & Betancourt, A. M. (2012). Mesenchymal stem cell one MSC1-Based therapy Attenuates Tumor growth whereas MSC2 treatment promotes tumor growth and Metastasis. PLoS ONE, 7(9), e45590.PubMedCentralPubMedGoogle Scholar
  112. 112.
    Waterman, R. S., et al. (2012). Anti-inflammatory mesenchymal stem cells (MSC2) attenuate symptoms of painful diabetic peripheral neuropathy. Stem Cells Translational Medicine, 1(7), 557–65.PubMedCentralPubMedGoogle Scholar
  113. 113.
    Boehm, U., et al. (1997). Cellular responses to interferon-gamma. Annual Review of Immunology, 15, 749–95.PubMedGoogle Scholar
  114. 114.
    Stagg, J., et al. (2006). Interferon-gamma-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell. Blood, 107(6), 2570–7.PubMedGoogle Scholar
  115. 115.
    English, K., et al. (2007). IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunology Letters, 110(2), 91–100.PubMedGoogle Scholar
  116. 116.
    Mellor, A. L., & Munn, D. H. (2000). Immunology at the maternal-fetal interface: lessons for T cell tolerance and suppression. Annual Review of Immunology, 18, 367–91.PubMedGoogle Scholar
  117. 117.
    Ge, W., et al. (2010). Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation, 90(12), 1312–20.Google Scholar
  118. 118.
    Spaggiari, G. M., et al. (2008). Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine two, three-dioxygenase and prostaglandin E2. Blood, 111(3), 1327–33.PubMedGoogle Scholar
  119. 119.
    Xu, G., et al. (2009). C/EBPbeta mediates synergistic upregulation of gene expression by interferon-gamma and tumor necrosis factor-alpha in bone marrow-derived mesenchymal stem cells. Stem Cells, 27(4), 942–8.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Zhang, S., et al. (2014). Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem cells in lipopolysaccharide-induced acute lung injury. Stem Cells. doi: 10.1002/stem.1632.
  121. 121.
    Nasir, G. A., et al. (2013). Mesenchymal stem cells and Interleukin-six attenuate liver fibrosis in mice. Journal of Translational Medicine, 11(1), 78.PubMedCentralPubMedGoogle Scholar
  122. 122.
    Sheng, H., et al. (2008). A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1. Cell Research, 18(8), 846–57.PubMedGoogle Scholar
  123. 123.
    Luo, Y., et al. (2012). Pretreating mesenchymal stem cells with interleukin-1beta and transforming growth factor-beta synergistically increases vascular endothelial growth factor production and improves mesenchymal stem cell-mediated myocardial protection after acute ischemia. Surgery, 151(3), 353–63.PubMedGoogle Scholar
  124. 124.
    Herrmann, J. L., et al. (2011). Transforming growth factor-alpha enhances stem cell-mediated postischemic myocardial protection. Annals of Thoracic Surgery, 92(5), 1719–25.PubMedGoogle Scholar
  125. 125.
    Wang, Y., et al. (2008). TGF-alpha increases human mesenchymal stem cell-secreted VEGF by MEK- and PI3-K- but not JNK- or ERK-dependent mechanisms. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 295(4), R1115–23.PubMedCentralPubMedGoogle Scholar
  126. 126.
    Chen, H. Y., et al. (2012). The protective effect of 17beta-estradiol against hydrogen peroxide-induced apoptosis on mesenchymal stem cell. Biomedicine and Pharmacotherapy, 66(1), 57–63.PubMedGoogle Scholar
  127. 127.
    Noiseux, N., et al. (2012). Preconditioning of stem cells by oxytocin to improve their therapeutic potential. Endocrinology, 153(11), 5361–72.PubMedGoogle Scholar
  128. 128.
    Xie, X. X., et al. (2012). Transplantation of Mesenchymal stem cells preconditioned with hydrogen sulfide enhances repair of myocardial infarction in rats. Tohoku Journal of Experimental Medicine, 226(1), 29–36.PubMedGoogle Scholar
  129. 129.
    Nasir, G. A., et al. (2013). Mesenchymal stem cells and Interleukin-six attenuate liver fibrosis in mice. Journal of Translational Medicine, 11, 78.PubMedCentralPubMedGoogle Scholar
  130. 130.
    Chen, S., et al. (2012). Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats. Journal of Surgical Research, 178(1), 81–91.PubMedGoogle Scholar
  131. 131.
    Bianco, P., et al. (2013). The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nature Medicine, 19(1), 35–42.PubMedCentralPubMedGoogle Scholar
  132. 132.
    Dreger, P., et al. (1995). Autologous progenitor cell transplantation: prior exposure to stem cell- toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. Blood, 86(10), 3970–3978.PubMedGoogle Scholar
  133. 133.
    Blazar, B., et al. (1988). Augmentation of donor bone marrow engraftment in histoincompatible murine recipients by granulocyte/macrophage colony-stimulating factor. Blood, 71(2), 320–328.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dean P. J. Kavanagh
    • 1
  • Joseph Robinson
    • 1
  • Neena Kalia
    • 1
  1. 1.Centre for Cardiovascular Science, Institute of Biomedical Research, The Medical SchoolUniversity of BirminghamBirminghamUK

Personalised recommendations