Yan DING, Ya Hong YUAN, Chun Fang ZHOU, Zhi Yong LU, Xiao Li WANG, Dongsheng LI

Intrabone marrow injection enhances placental mesenchymal stem cellmediated support of hematopoiesis in mice

Background/aim: In order to determine the synergistic effects of human placental mesenchymal stem cells (PMSCs) on hematopoiesis in vivo, we compared the intrabone marrow injection (IBMI) with the conventional intravenous injection (IVI). Materials and methods: C57BL/6 recipient mice conditioned with lethal doses of irradiation were transplanted with bone marrow mononuclear cells (MNCs) and bone marrow-derived mesenchymal stem cells (BMSCs) from BALB/c mice by IBMI or IVI. NOD/ SCID recipient mice conditioned with sublethal doses of irradiation were transplanted with human umbilical cord blood MNCs (UCBMNCs) and PMSCs by IBMI or IVI. Results: The number of hematopoietic cells was significantly higher in mice transplanted with BMSCs by IBMI than in those transplanted by IVI in a murine transplantation model (BALB/c→C57BL/6). Moreover, the percentage of human hematopoietic cells in the tibiae of the NOD/SCID mice that were transplanted with PMSCs plus UCB-MNCs was higher than that in mice transplanted with UCB-MNCs alone. In addition, in mice that were transplanted with PMSCs, PMSCs injected by IBMI were more efficient than those injected by IVI. Conclusion: Our results not only elucidated the role of PMSCs in promoting hematopoiesis, but also revealed the therapeutic potential of the combination of PMSCs and IBMI in transplantation.

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1. Bregni M, Dodero A, Peccatori J, Pescarollo A, Bernardi M, Sassi I, Voena C, Zaniboni A, Bordignon C, Corradini P. Nonmyeloablative conditioning followed hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 2002; 99: 42344236.
2. Ikehara S. A novel method of bone marrow transplantation (BMT) for intractable autoimmune diseases. J Autoimmun 2008; 30: 108115.
3. Thomas ED, Buckner CD, Clift RA, Fefer A, Johnson FL, Neiman PE, Sale GE, Sanders JE, Singer JW, Shulman H et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med 1979; 301: 597599.
4. Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support longterm hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res 2000; 9: 841 848.
5. Zhu GR, Zhou XY, Lu H, Zhou JW, Li AP, Xu W, Li JY, Wang CY. Human bone marrow mesenchymal stem cells express multiple hematopoietic growth factors. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2003; 11: 115119.
6. Devine SM. Mesenchymal stem cells: will they have a role in the clinic? J Cell Biochem Suppl 2002; 38: 7379.
7. Li Y, Chen S, Yuan J, Yang Y, Li J, Ma J, Wu X, Freund M, Pollok K, Hanenberg H et al. Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg-/- mice in vivo. Blood 2009; 113: 23422351.
8. Angelopoulou M, Novelli E, Grove JE, Rinder HM, Civin C, Cheng L, Krause DS. Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice. Exp Hematol 2003; 31: 413420.
9. Koç ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM. Rapid hematopoietic recovery after coinfusion of autologous- blood stem cells and cultureexpanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000; 18: 307316. 18: 307316.
10. Noort WA, Kruisselbrink AB, int Anker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MH, Löwik CW, Falkenburg JH, Willemze R et al. Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 2002; 30: 870878.
11. int Anker PS, Noort WA, Kruisselbrink AB, Scherjon SA, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE. Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 2003; 31: 881889.
12. Bensidhoum M, Chapel A, Francois S, Demarquay C, Mazurier C, Fouillard L, Bouchet S, Bertho JM, Gourmelon P, Aigueperse J et al. Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood 2004; 103: 33133319.
13. van Hennik PB, de Koning AE, Ploemacher RE. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment. Blood 1999; 94: 30553061.
14. Cashman JD, Eaves CJ. High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/ SCID mice. Blood 2000; 96: 39793981.
15. Panoskaltsis-Mortari A, Price A, Hermanson JR, Taras E, Lees C, Serody JS, Blazar BR. In vivo imaging of graft-versus-hostdisease in mice. Blood 2004; 103: 35903598.
16. Kushida T, Inaba M, Hisha H, Ichioka N, Esumi T, Ogawa R, Iida H, Ikehara S. Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice. Blood 2001; 97: 32923299.
17. Parolini O, Alviano F, Bagnara GP, Bilic G, Bühring HJ, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N et al. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells 2008; 26: 300311.
18. Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 2006; 194: 664673.
19. Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, Shun CT, Yen ML, Lee MC, Chen YC. Isolation of multipotent cells from human term placenta. Stem Cells 2005; 23: 39.
20. Celebi B, Mantovani D, Pineault N. Irradiated mesenchymal stem cells improve the ex vivo expansion of hematopoietic progenitors by partly mimicking the bone marrow endosteal environment. J Immunol Methods 2011; 370: 93103.
21. Li Q, Hisha H, Yasumizu R, Fan TX, Yang GX, Li Q, Cui YZ, Wang XL, Song CY, Okazaki S et al. Analyses of very early hemopoietic regeneration after bone marrow transplantation: comparison of intravenous and intrabone marrow routes. Stem Cells 2007; 25: 11861194.
22. Leisten I, Kramann R, Ventura Ferreira MS, Bovi M, Neuss S, Ziegler P, Wagner W, Knüchel R, Schneider RK. 3D coculture of hematopoietic stem and progenitor cells and mesenchymal stem cells in collagen scaffolds as a model of the hematopoietic niche. Biomaterials 2012; 33: 17361747.
23. Masuda S, Ageyama N, Shibata H, Obara Y, Ikeda T, Takeuchi K, Ueda Y, Ozawa K, Hanazono Y. Cotransplantation with MSCs improves engraftment of HSCs after autologous intrabone marrow transplantation in nonhuman primates. Exp Hematol 2009; 37: 12501257.
24. Wynn RF, Hart CA, Corradi-Perini C, ONeill L, Evans CA, Wraith JE, Fairbairn LJ, Bellantuono I. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 2004; 104: 26432645.
25. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells 2006; 24: 10301041.
26. Lee RH, Hsu SC, Munoz J, Jung JS, Lee NR, Pochampally R, Prockop DJ. A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice. Blood 2006; 107: 21532161.
27. Lapidot T, Kollet O. The essential roles of the chemokine SDF- 1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m (null) mice. Leukemia 2002; 16: 1992 2003.
28. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 1999; 283: 845848.
29. Pontikoglou C, Deschaseaux F, Sensebé L, Papadaki HA. Bone marrow mesenchymal stem cells: biological properties and their role in hematopoiesis and hematopoietic stem cell transplantation. Stem Cell Rev 2011; 7: 569589.
30. Spivey WH. Intraosseous infusions. J Pediatr 1987; 111: 639 643.
31. Smith R, Davis N, Bouamra O, Lecky F. The utilisation of intraosseous infusion in the resuscitation of paediatric major trauma patients. Injury 2005; 36: 10341039.
32. Josefson A. A new method of treatment-intraossal injections. Acta Medica Scandinavica 1934; 81: 550564.
33. Tocantins L, ONeill J, Jones H. Infusions of blood and other fluids via the bone marrow: application in pediatrics. JAMA 1941; 117: 12291234.
34. Ramirez PA, Wagner JE, Brunstein CG. Going straight to the point: intra-BM injection of hematopoietic progenitors. Bone Marrow Transplant 2010; 45: 11271133.
35. Frassoni F, Varaldo R, Gualandi F, Bacigalupo A, Sambuceti G, Sacchi N, Podestà M. The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases. Best Pract Res Clin Haematol 2010; 23: 237244.