Endometrial Regenerative Cells and Exosomes Thereof for Treatment of Radiation Exposure

Chapter

Abstract

In 2007, we discovered a novel subset of mesenchymal stem cells (MSCs) derived from the endometrium, termed “endometrial regenerative cells (ERC).” In comparison to other MSC types (e.g., bone marrow and adipose), ERC possess (a) more rapid proliferative rate, (b) higher levels of growth factor production (VEGF, GM-CSF, PDGF), and (c) higher angiogenic activity. We are currently running two clinical trials for these cells in patients with critical limb ischemia and heart failure.

Keywords

Toxicity Ischemia Leukemia Iodine Triad 

References

  1. 1.
    Manthous CA, Jackson Jr WL. The 9-11 Commission’s invitation to imagine: a pathophysiology-based approach to critical care of nuclear explosion victims. Crit Care Med. 2007;35(3):716–23.PubMedCrossRefGoogle Scholar
  2. 2.
    Ross JR, et al. Radiation injury treatment network (RITN): healthcare professionals preparing for a mass casualty radiological or nuclear incident. Int J Radiat Biol. 2011;87(8):748–53.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Heslet L, Bay C, Nepper-Christensen S. Acute radiation syndrome (ARS) – treatment of the reduced host defense. Int J Gen Med. 2012;5:105–15.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Herodin F, et al. Which place for stem cell therapy in the treatment of acute radiation syndrome? Folia Histochem Cytobiol. 2005;43(4):223–7.PubMedGoogle Scholar
  5. 5.
    Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007;12(6):738–47.PubMedCrossRefGoogle Scholar
  6. 6.
    Mettler Jr FA, et al. Can radiation risks to patients be reduced without reducing radiation exposure? The status of chemical radioprotectants. AJR Am J Roentgenol. 2011;196(3):616–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Galotto M, et al. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Exp Hematol. 1999;27(9):1460–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Banfi A, et al. Bone marrow stromal damage after chemo/radiotherapy: occurrence, consequences and possibilities of treatment. Leuk Lymphoma. 2001;42(5):863–70.PubMedCrossRefGoogle Scholar
  9. 9.
    Almeida-Porada G, et al. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95(11):3620–7.PubMedGoogle Scholar
  10. 10.
    Noort WA, et al. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2002;30(8):870–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Francois S, et al. Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells. 2006;24(4):1020–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhuo W, et al. Mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal dysfunction by improving the antioxidant/oxidant balance in the ischemic kidney. Urol Int. 2011;86(2):191–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Nightingale H, et al. Changes in expression of the antioxidant enzyme SOD3 occur upon differentiation of human bone marrow-derived mesenchymal stem cells in vitro. Stem Cells Dev. 2012;21:2026–35.PubMedCrossRefGoogle Scholar
  14. 14.
    Wei L, et al. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis. 2012;46:635–45.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Crisostomo PR, et al. Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am J Physiol Cell Physiol. 2008;294(3):C675–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang M, et al. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006;291(4):R880–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Mouiseddine M, et al. Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model. Br J Radiol. 2007;80(Spec No 1):S49–55.PubMedCrossRefGoogle Scholar
  18. 18.
    Lazarus HM, et al. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995;16(4):557–64.PubMedGoogle Scholar
  19. 19.
    Koc ON, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307–16.PubMedGoogle Scholar
  20. 20.
    Lazarus HM, et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005;11(5):389–98.PubMedCrossRefGoogle Scholar
  21. 21.
    Ball LM, et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation. Blood. 2007;110(7):2764–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Baron F, et al. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010;16(6):838–47.PubMedCrossRefGoogle Scholar
  23. 23.
    Tolar J, et al. Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells. 2010;28(8):1446–55.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Yang X, et al. Marrow stromal cell infusion rescues hematopoiesis in lethally irradiated mice despite rapid clearance after infusion. Adv Hematol. 2012;2012:142530.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Lange C, et al. Radiation rescue: mesenchymal stromal cells protect from lethal irradiation. PLoS One. 2011;6(1):e14486.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Hu KX, et al. The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury. Br J Radiol. 2010;83(985):52–8.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Saha S, et al. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice. PLoS One. 2011;6(9):e24072.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Honmou O, et al. Mesenchymal stem cells: therapeutic outlook for stroke. Trends Mol Med. 2012;18(5):292–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Ali Khalili M, et al. Therapeutic benefit of intravenous transplantation of mesenchymal stem cells after experimental subarachnoid hemorrhage in rats. J Stroke Cerebrovasc Dis. 2011;21(6):445–51.CrossRefGoogle Scholar
  30. 30.
    Bao X, et al. Transplantation of Flk-1+ human bone marrow-derived mesenchymal stem cells promotes angiogenesis and neurogenesis after cerebral ischemia in rats. Eur J Neurosci. 2011;34(1):87–98.PubMedCrossRefGoogle Scholar
  31. 31.
    Huang TT. Redox balance- and radiation-mediated alteration in hippocampal neurogenesis. Free Radic Res. 2012;46:951–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Tzouvelekis A, Antoniadis A, Bouros D. Stem cell therapy in pulmonary fibrosis. Curr Opin Pulm Med. 2011;17(5):368–73.PubMedCrossRefGoogle Scholar
  33. 33.
    Nemeth K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–9.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Meng X, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med. 2007;5:57.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Patel AN, et al. Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant. 2008;17(3):303–11.PubMedCrossRefGoogle Scholar
  36. 36.
    Hida N, et al. Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem Cells. 2008;26(7):1695–704.PubMedCrossRefGoogle Scholar
  37. 37.
    Zhong Z, et al. Feasibility investigation of allogeneic endometrial regenerative cells. J Transl Med. 2009;7:15.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Ichim TE, et al. Mesenchymal stem cells as anti-inflammatories: implications for treatment of Duchenne muscular dystrophy. Cell Immunol. 2010;260(2):75–82.PubMedCrossRefGoogle Scholar
  39. 39.
    Ichim TE, et al. Combination stem cell therapy for heart failure. Int Arch Med. 2010;3(1):5.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Murphy MP, et al. Allogeneic endometrial regenerative cells: an “Off the shelf solution” for critical limb ischemia? J Transl Med. 2008;6:45.Google Scholar
  41. 41.
    Borlongan CV, et al. Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev. 2010;19(4):439–52.Google Scholar
  42. 42.
    Wolff EF, et al. Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model. J Cell Mol Med. 2011;15(4):747–55.Google Scholar
  43. 43.
    Santamaria X, et al. Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol Ther. 2011;19(11):2065–71.Google Scholar
  44. 44.
    Wu X, et al. Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice. Stem Cells Dev. 2014;23(11):1245–57.Google Scholar
  45. 45.
    Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.PubMedCrossRefGoogle Scholar
  46. 46.
    Alonso R, et al. Diacylglycerol kinase alpha regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell Death Differ. 2011;18(7):1161–73.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Zhang H, et al. CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity. Cell Mol Immunol. 2011;8(1):23–30.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Mathews JA, et al. CD23 Sheddase A disintegrin and metalloproteinase 10 (ADAM10) is also required for CD23 sorting into B cell-derived exosomes. J Biol Chem. 2010;285(48):37531–41.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Buschow SI, et al. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol Cell Biol. 2010;88(8):851–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Hwang I, Ki D. Receptor-mediated T cell absorption of antigen presenting cell-derived molecules. Front Biosci. 2011;16:411–21.CrossRefGoogle Scholar
  51. 51.
    Viaud S, et al. Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-gamma. J Immunother. 2011;34(1):65–75.PubMedCrossRefGoogle Scholar
  52. 52.
    Clayton A, et al. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol. 2011;187(2):676–83.PubMedCrossRefGoogle Scholar
  53. 53.
    Battke C, et al. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother. 2011;60(5):639–48.PubMedCrossRefGoogle Scholar
  54. 54.
    Lachenal G, et al. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci. 2011;46(2):409–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Faure J, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006;31(4):642–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Fitzner D, et al. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci. 2011;124(Pt 3):447–58.PubMedCrossRefGoogle Scholar
  57. 57.
    Mincheva-Nilsson L, Baranov V. The role of placental exosomes in reproduction. Am J Reprod Immunol. 2010;63(6):520–33.PubMedCrossRefGoogle Scholar
  58. 58.
    Sahoo S, et al. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res. 2011;109(7):724–8.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med. 2011;6(4):481–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2015

Authors and Affiliations

  1. 1.Biotechnology DivisionCromos PharmaLongviewUSA
  2. 2.Regen BioPharmaLa MesaUSA

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