Chimerism of bone marrow mesenchymal stem/ stromal cells in allogeneic hematopoietic cell transplantation: Is it clinically relevant?

Chimerism

Volumn 4, Issue 3, 2013, Pages

  Miura, Yasuo ^a   Yoshioka, Satoshi ^a,b   Yao, Hisayuki ^a   Takaori Kondo, Akifumi ^a,b   Maekawa, Taira ^a   Ichinohe, Tatsuo ^c  

^a KYOTO UNIVERSITY HOSPITAL   (Japan)

^b KYOTO UNIVERSITY   (Japan)

^c HIROSHIMA UNIVERSITY   (Japan)

Author keywords

Graft versus host disease; Hematopoietic cell transplantation; Hematopoietic reconstitution; Mesenchymal stem stromal cells; Stem cell niches

Indexed keywords

ANTINEOPLASTIC AGENT; STEROID;

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; BIOLOGICAL ACTIVITY; BREAST CANCER; CHIMERA; DRUG MEGADOSE; ENGRAFTMENT; EX VIVO STUDY; GRAFT VERSUS HOST REACTION; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOMODULATION; MESENCHYMAL STEM CELL; MESENCHYMAL STROMA CELL; MULTIPOTENT STEM CELL; NONHUMAN; OSTEOGENESIS IMPERFECTA; REVIEW; STEM CELL EXPANSION; STEM CELL NICHE; TISSUE REGENERATION; ALLOTRANSPLANTATION; BONE MARROW; HEMATOPOIETIC STEM CELL TRANSPLANTATION; IMMUNE SYSTEM DISEASES; IMMUNOLOGY; MESENCHYMAL STEM CELL TRANSPLANTATION; PHYSIOLOGY; REGENERATION; TRANSPLANTATION CONDITIONING; TRANSPLANTATION TOLERANCE; TUMOR MICROENVIRONMENT; GRAFT-VERSUS-HOST DISEASE; HEMATOPOIETIC CELL TRANSPLANTATION; HEMATOPOIETIC RECONSTITUTION; IMMUNOPATHOLOGY; IMMUNOSUPPRESSIVE TREATMENT; MESENCHYMAL STEM/STROMAL CELLS; STEM CELL NICHES;

BONE MARROW; CELLULAR MICROENVIRONMENT; CHIMERISM; GRAFT VS HOST DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNE SYSTEM DISEASES; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; REGENERATION; TRANSPLANTATION CONDITIONING; TRANSPLANTATION TOLERANCE; TRANSPLANTATION, HOMOLOGOUS;

GRAFT-VERSUS-HOST DISEASE; HEMATOPOIETIC CELL TRANSPLANTATION; HEMATOPOIETIC RECONSTITUTION; MESENCHYMAL STEM/STROMAL CELLS; STEM CELL NICHES;

EID: 84880753022     PISSN: 19381956     EISSN: 19381964     Source Type: Journal    
DOI: 10.4161/chim.25609     Document Type: Review

References (72)

1. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968; 6:230-47; PMID:5654088; http://dx.doi.org/10.1097/00007890-196803000-00009
2. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9:641-50; PMID:1870029; http://dx.doi. org/10.1002/jor.1100090504
3. Frenette PS, Pinho S, Lucas D, Scheiermann C. Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine. Annu Rev Immunol 2013; 31:285-316; PMID:23298209; http://dx.doi.org/10.1146/annurevimmunol-032712-095919
4. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8:726-36; PMID:19172693; http://dx.doi.org/10.1038/ nri2395
5. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315-7; PMID:16923606; http://dx.doi.org/10.1080/14653240600855905
6. Bieback K, Kern S, Klüter H, Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 2004; 22:625-34; PMID:15277708; http://dx.doi.org/10.1634/ stemcells.22-4-625
7. Zhang X, Hirai M, Cantero S, Ciubotariu R, Dobrila L, Hirsh A, et al. Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymal stem cells from bone marrow and adipose tissue. J Cell Biochem 2011; 112:1206-18; PMID:21312238; http://dx.doi. org/10.1002/jcb.23042
8. Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, et al. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells 2005; 23:1105-12; PMID:15955825; http://dx.doi.org/10.1634/ stemcells.2004-0330
9. Cesselli D, Beltrami AP, Rigo S, Bergamin N, D'Aurizio F, Verardo R, et al. Multipotent progenitor cells are present in human peripheral blood. Circ Res 2009; 104:1225-34; PMID:19390058; http://dx.doi. org/10.1161/CIRCRESAHA.109.195859
10. Fernández M, Simon V, Herrera G, Cao C, Del Favero H, Minguell JJ. Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients. Bone Marrow Transplant 1997; 20:265-71; PMID:9285540; http://dx.doi.org/10.1038/ sj.bmt.1700890
11. Dalle Carbonare L, Valenti MT, Zanatta M, Donatelli L, Lo Cascio V. Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Arthritis Rheum 2009; 60:3356-65; PMID:19877060; http://dx.doi.org/10.1002/ art.24884
12. Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 2009; 88:792-806; PMID:19767575; http:// dx.doi.org/10.1177/0022034509340867
13. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res 2003; 18:696-704; PMID:12674330; http://dx.doi.org/10.1359/ jbmr.2003.18.4.696
14. Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med 2005; 352:1959-66; PMID:15888696; http://dx.doi.org/10.1056/ NEJMoa044264
15. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838-43; PMID:11986244; http:// dx.doi.org/10.1182/blood.V99.10.3838
16. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107:367-72; PMID:16141348; http://dx.doi. org/10.1182/blood-2005-07-2657
17. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-22; PMID:15494428; http://dx.doi. org/10.1182/blood-2004-04-1559
18. Jones S, Horwood N, Cope A, Dazzi F. The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells. J Immunol 2007; 179:2824-31; PMID:17709496
19. Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi 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; 15:42-9; PMID:19098906; http://dx.doi.org/10.1038/nm.1905
20. Groh ME, Maitra B, Szekely E, Koç ON. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 2005; 33:928-34; PMID:16038786; http://dx.doi. org/10.1016/j.exphem.2005.05.002
21. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2:141-50; PMID:18371435; http://dx.doi.org/10.1016/j. stem.2007.11.014
22. Kortesidis A, Zannettino A, Isenmann S, Shi S, Lapidot T, Gronthos S. Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood 2005; 105:3793-801; PMID:15677562; http://dx.doi.org/10.1182/blood-2004-11-4349
23. Ji JF, He BP, Dheen ST, Tay SS. Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury. Stem Cells 2004; 22:415-27; PMID:15153618; http://dx.doi. org/10.1634/stemcells.22-3-415
24. Wynn RF, Hart CA, Corradi-Perini C, O'Neill L, Evans CA, Wraith JE, et al. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 2004; 104:2643-5; PMID:15251986; http://dx.doi.org/10.1182/blood-2004-02-0526
25. Sato K, Ozaki K, Oh I, Meguro A, Hatanaka K, Nagai T, et al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 2007; 109:228-34; PMID:16985180; http:// dx.doi.org/10.1182/blood-2006-02-002246
26. Meisel R, Zibert A, Laryea M, Göbel U, Däubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103:4619-21; PMID:15001472; http:// dx.doi.org/10.1182/blood-2003-11-3909
27. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006; 24:386-98; PMID:16123384; http://dx.doi.org/10.1634/stemcells.2005-0008
28. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 2008; 111:1327-33; PMID:17951526; http://dx.doi.org/10.1182/ blood-2007-02-074997
29. Chabannes D, Hill M, Merieau E, Rossignol J, Brion R, Soulillou JP, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007; 110:3691-4; PMID:17684157; http://dx.doi.org/10.1182/blood-2007-02-075481
30. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-22; PMID:15494428; http://dx.doi. org/10.1182/blood-2004-04-1559
31. Jarvinen L, Badri L, Wettlaufer S, Ohtsuka T, Standiford TJ, Toews GB, et al. Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator. J Immunol 2008; 181:4389-96; PMID:18768898
32. Nasef A, Mazurier C, Bouchet S, François S, Chapel A, Thierry D, et al. Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression. Cell Immunol 2008; 253:16-22; PMID:18639869; http://dx.doi.org/10.1016/j.cellimm.2008.06.002
33. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006; 24:74-85; PMID:16099998; http://dx.doi. org/10.1634/stemcells.2004-0359
34. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocytederived dendritic cells. J Immunol 2006; 177:2080-7; PMID:16887966
35. Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSCderived prostaglandin E2. Blood 2009; 113:6576-83; PMID:19398717; http://dx.doi.org/10.1182/blood-2009-02-203943
36. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31:890-6; PMID:14550804; http://dx.doi.org/10.1016/S0301-472X(03)00110-3
37. Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 2006; 107:1484-90; PMID:16239427; http://dx.doi. org/10.1182/blood-2005-07-2775
38. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439-41; PMID:15121408; http://dx.doi.org/10.1016/S0140-6736(04)16104-7
39. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al.; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371:1579-86; PMID:18468541; http://dx.doi.org/10.1016/S0140-6736(08)60690-X
40. Prockop DJ. Repair of tissues by adult stem/progenitor cells (MSCs): controversies, myths, and changing paradigms. Mol Ther 2009; 17:939-46; PMID:19337235; http://dx.doi.org/10.1038/mt.2009.62
41. Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med 2010; 14:2190-9; PMID:20716123; http://dx.doi.org/10.1111/j.1582-4934.2010.01151.x
42. Méndez-Ferrer S, Michiurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and hematopoietic stem cells from a unique bone marrow niche. Nature 2012; 466:829-34; http://dx.doi. org/10.1038/nature09262
43. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 2007; 131:324-36; PMID:17956733; http://dx.doi.org/10.1016/j. cell.2007.08.025
44. Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K, et al. The essential functions of adipoosteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 2010; 33:387-99; PMID:20850355; http://dx.doi.org/10.1016/j.immuni.2010.08.017
45. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 2010; 464:852-7; PMID:20305640; http://dx.doi.org/10.1038/nature08851
46. Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell 2007; 129:1097-110; PMID:17574023; http://dx.doi.org/10.1016/j. cell.2007.05.014
47. Walkley CR, Shea JM, Sims NA, Purton LE, Orkin SH. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell 2007; 129:1081-95; PMID:17574022; http:// dx.doi.org/10.1016/j.cell.2007.03.055
48. Miura M, Chen XD, Allen MR, Bi Y, Gronthos S, Seo BM, et al. A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. J Clin Invest 2004; 114:1704-13; PMID:15599395
49. Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI. 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; 16:557-64; PMID:8528172
50. Koç ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, 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 highdose chemotherapy. J Clin Oncol 2000; 18:307-16; PMID:10637244
51. Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, et al. Cotransplantation of HLAidentical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 2005; 11:389-98; PMID:15846293; http://dx.doi. org/10.1016/j.bbmt.2005.02.001
52. Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, et al. Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 2007; 21:1733-8; PMID:17541394; http://dx.doi.org/10.1038/ sj.leu.2404777
53. Ball LM, Bernardo ME, Roelofs H, Lankester A, Cometa A, Egeler RM, 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; 110:2764-7; PMID:17638847; http://dx.doi.org/10.1182/blood-2007-04-087056
54. Macmillan ML, Blazar BR, DeFor TE, Wagner JE. Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I-II clinical trial. Bone Marrow Transplant 2009; 43:447-54; PMID:18955980; http://dx.doi.org/10.1038/ bmt.2008.348
55. de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M, et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med 2012; 367:2305-15; PMID:23234514; http://dx.doi. org/10.1056/NEJMoa1207285
56. Lange C, Kaltz C, Thalmeier K, Kolb HJ, Huss R. Hematopoietic reconstitution of syngeneic mice with a peripheral blood-derived, monoclonal CD34-, Sca-1+, Thy-1(low), c-kit+ stem cell line. J Hematother Stem Cell Res 1999; 8:335-42; PMID:10634171; http:// dx.doi.org/10.1089/152581699320090
57. Bartsch K, Al-Ali H, Reinhardt A, Franke C, Hudecek M, Kamprad M, et al. Mesenchymal stem cells remain host-derived independent of the source of the stem-cell graft and conditioning regimen used. Transplantation 2009; 87:217-21; PMID:19155975; http://dx.doi. org/10.1097/TP.0b013e3181938998
58. García-Castro J, Balas A, Ramírez M, Pérez-Martínez A, Madero L, González-Vicent M, et al. Mesenchymal stem cells are of recipient origin in pediatric transplantations using umbilical cord blood, peripheral blood, or bone marrow. J Pediatr Hematol Oncol 2007; 29:388-92; PMID:17551400; http://dx.doi.org/10.1097/ MPH.0b013e3180645186
59. Pozzi S, Lisini D, Podestà M, Bernardo ME, Sessarego N, Piaggio G, et al. Donor multipotent mesenchymal stromal cells may engraft in pediatric patients given either cord blood or bone marrow transplantation. Exp Hematol 2006; 34:934-42; PMID:16797421; http:// dx.doi.org/10.1016/j.exphem.2006.03.007
60. Poloni A, Leoni P, Buscemi L, Balducci F, Pasquini R, Masia MC, et al. Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen. Leukemia 2006; 20:329-35; PMID:16341047; http://dx.doi.org/10.1038/ sj.leu.2404018
61. Dickhut A, Schwerdtfeger R, Kuklick L, Ritter M, Thiede C, Neubauer A, et al. Mesenchymal stem cells obtained after bone marrow transplantation or peripheral blood stem cell transplantation originate from host tissue. Ann Hematol 2005; 84:722-7; PMID:16132912; http://dx.doi.org/10.1007/s00277-005-1067-8
62. Rieger K, Marinets O, Fietz T, Körper S, Sommer D, Mücke C, et al. Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation. Exp Hematol 2005; 33:605-11; PMID:15850839; http:// dx.doi.org/10.1016/j.exphem.2005.02.004
63. Villaron EM, Almeida J, López-Holgado N, Alcoceba M, Sánchez-Abarca LI, Sanchez-Guijo FM, et al. Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematologica 2004; 89:1421-7; PMID:15590390
64. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5:309-13; PMID:10086387; http://dx.doi. org/10.1038/6529
65. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 2002; 99:8932-7; PMID:12084934; http:// dx.doi.org/10.1073/pnas.132252399
66. Li SC, Tachiki LM, Luo J, Dethlefs BA, Chen Z, Loudon WG. A biological global positioning system: considerations for tracking stem cell behaviors in the whole body. Stem Cell Rev 2010; 6:317-33; PMID:20237964; http://dx.doi.org/10.1007/s12015-010-9130-9
67. Allers C, Sierralta WD, Neubauer S, Rivera F, Minguell JJ, Conget PA. Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice. Transplantation 2004; 78:503-8; PMID:15446307; http://dx.doi.org/10.1097/01.TP.0000128334.93343. B3
68. Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003; 108:863-8; PMID:12900340; http://dx.doi.org/10.1161/01. CIR.0000084828.50310.6A
69. Ikehara S. A novel BMT technique for treatment of various currently intractable diseases. Best Pract Res Clin Haematol 2011; 24:477-83; PMID:21925101; http://dx.doi.org/10.1016/j.beha.2011.04.003
70. Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, et al. Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One 2008; 3:e2615; PMID:18612428; http:// dx.doi.org/10.1371/journal.pone.0002615
71. Yamaza T, Miura Y, Akiyama K, Bi Y, Sonoyama W, Gronthos S, et al. Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice. Blood 2009; 113:2595-604; PMID:19074727; http://dx.doi. org/10.1182/blood-2008-10-182246
72. Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG, et al. Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol 2002; 20:587-91; PMID:12042862; http://dx.doi.org/10.1038/ nbt0602-587