Mesenchymal stromal cells

Current Opinion in Hematology

Volumn 13, Issue 6, 2006, Pages 419-425

  Keating, Armand ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

Graft versus host disease; Immune suppression; Marrow stromal cells; Mesenchymal stem cells; Nonimmunogenicity

Indexed keywords

BLEOMYCIN; INDOMETACIN;

ADOPTIVE IMMUNOTHERAPY; CELL DIFFERENTIATION; CELL LINEAGE; CELL POPULATION; CLINICAL TRIAL; GRAFT VERSUS HOST REACTION; HEART MUSCLE; HEMATOPOIESIS; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; MESENCHYME CELL; NONHUMAN; OSTEOGENESIS IMPERFECTA; PARACRINE SIGNALING; PRIORITY JOURNAL; REVIEW; STROMA CELL; TISSUE REPAIR;

ANIMALS; CELL DIFFERENTIATION; GRAFT VS HOST DISEASE; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STEM CELLS; MICE; STROMAL CELLS; TERMINOLOGY; TERMINOLOGY AS TOPIC;

EID: 33750223518     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/01.moh.0000245697.54887.6f     Document Type: Review

References (67)

1. Dexter TM, Spooncer E, Schofield, et al. Hematopoietic stem cells and the problem of self-renewal. Blood Cells 1984; 10:315-339.
2. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143-147.
3. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000; 164:247-256.
4. Weng YS, Lin HY, Hsiang YJ, et al. The effects of different growth factors on human bone marrow stromal cells differentiating into hepatocyte-like cells. Adv Exp Med Biol 2003; 534:119-128.
5. Toma C, Pittenger MF, Cahill KS, et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002; 105:93-98.
6. Friedenstein AJ, Chailakhyan RK, Latsinik NV, et al. Stromal cells responsible for transferring the microenvironment of the hematopoietic tissues: cloning in vitro and retransplantation in vivo. Transplantation 1974; 17:331-340.
7. Keating A, Singer JW, Killen PD, et al. Donor origin of the in vitro hematopoietic microenvironment after marrow transplantation in man. Nature 1982; 298:280-283.
8. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13:4279-4295.
9. Sarugaser R, Lickorish D, Baksh D, et al. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 2005; 23:220-229. Highly proliferative population from a readily available source that would otherwise be discarded. Human umbilical cord perivascular cells share many of the characteristics of bone marrow derived MSCs.
10. Shih DT, Lee DC, Chen SC, et al. Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue. Stem Cells 2005; 7:1012-1020.
11. In't Anker PS, Scherjon SA, Kleijburg-van der Keur C, et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem cells 2004; 22:1338-1345.
12. In't Anker PS, Noort WA, Scherjon SA, et al. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung and spleen exhibit a similar immunophenotype but a heterogeneuous multilineage differentiation potential. Haematologica 2003; 88:845-852.
13. Horwitz EM, Le Blanc K, Dominici M, et al. Clarification of the nomenclature for MSC: the international Society for Cellular Therapy position statement. Cytotherapy 2005; 7:393-395. Helpful recommendation regarding nomenclature: not all MSCs are true stem cells. The term stem cell should be used rigorously.
14. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy (in press).
15. Gregory CA, Prockop DJ, Spees JL. Non-hematopoietic bone marrow stem cells: molecular control of expansion and differentiation. Exp Cell Res 2005; 306:330-335. A good review of basic practical MSC biology.
16. Gregory CA, Singh H, Prockop DJ. The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem 2003; 278:28067-28078.
17. Gregory CA, Perry AS, Reyes E, et al. Dkk-1-derived synthetic peptides and lithium chloride for the control and recovery of adult stem cells from bone marrow. J Biol Chem 2005; 280:2309-2323. Proliferation and differentiation of MSCs may be amenable to pharmacological manipulation.
18. Colter DC, Sekiya I, Prockop DJ. Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 2001; 98:7841-7845.
19. Lee HL, Hsu SC, Munoz J, et al. A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice. Blood 2006; 107:2153-2161. An important advance in understanding the biology of MSCs.
20. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30:42-48.
21. Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31:890-896.
22. Maitra B, Szekely E, Gjini K, et al. Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant 2004; 33:597-604.
23. Keating A, Powell J, Takahashi M, Singer JW. The generation of human longterm marrow cultures from marrow depleted of Ia (HLA-DR) positive cells. Blood 1984; 64:1159-1162.
24. Singer JW, Keating A, Wright TH. The human hematopoietic microenvironment. In: Hoffbrand V, editor. Advances in haematology, 4. London: Churchill Livingstone; 1984. pp. 1-24.
25. Gotherstrom C, Ringden O, Tammik C, et al. Immunologic properties of human fetal mesenchymal stem cells. Am J Obstet Gynecol 2004; 190:239-245.
26. Tse WT, Pendleton JD, Beyer WM, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75:389-397.
27. Klyushnenkova E, Mosca JD, Zernetkina V, et al. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 2005; 12:47-57. Well designed experiments indicating that immune inertness of MSCs is not due to absence of costimulatory molecules.
28. Eliopoulos N, Stagg J, Lejeune L, et al. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood 2005; 106:4057-4065. Important study that needs to be confirmed suggesting that MSCs are immunogenic and raises doubts about allogeneic MSCs as universal donor cells. A key question is whether or not these data can be extrapolated to humans.
29. Lui H, Kemery DM, Heng BC, Ouyang HW, et al. The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells. J Immunol 2006; 176:2864-2871. This interesting rabbit model indicates that the osteogenic progeny of MSCs which acquire HLA class II molecules in vivo remain nonimmunogenic but lose their immune suppressive activity.
30. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003; 101:3722-3729.
31. Suck G, Branch DR, Smyth MJ, et al. KHYG-1, a model for the study of enhanced natural killer cell cytotoxicity. Exp Hematol 2005; 33:1160-1171.
32. Rasmusson I, Ringden O, Sundberg B, LeBlanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76:1208-1213.
33. Spaggiari GM, Capobiance A, Becchetti S, et al. 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; 107:1484-1490. Good study providing a mechanistic basis for lysis of MSCs by natural killer cells; requires prolonged activation of natural killer cells with IL-2 to show the effect in vitro but does it square with clinical observations?
34. Keating A, Filshie R, Mollee P, Wang X-H. Prolonged engraftment and transgene expression of genetically modified autologous bone marrow stromal (mesenchymal) cells after infusion post autotransplant: a platform for cell and gene therapy. Blood 2001; 98:832a.
35. Saito T, Kuang JQ, Bittira B, et al. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 2002; 74:19-24.
36. Grinemmo KH, Mansson A, Dellgren G, et al. Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. J Thorac Cardiovasc Surg 2004; 127:1293-1300.
37. Potian JA, Aviv H, Ponzio NM, et al. Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. J Immunol 2003; 171:3426-3434.
38. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838-3843.
39. Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 2003; 57:11-20.
40. Le Blanc K, Rasmusson I, Gotherstrom C, et al. Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol 2004; 60:307-315.
41. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105:1815-1822. Key recent publication displaying the complexity of mechanisms underlying immune suppression by MSCs.
42. Rasmusson I, Ringden O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 2005; 305:33-41. Mechanism of MSC-mediated suppression is complex and depends on the type of T-cell stimuli.
43. Meisel R, Zibert A, Layrea M, et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2002; 103:4619-4621.
44. Plumas J, Chaperot L, Richard MJ, et al. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 2005; 19:1597-1604. Another mechanism for T-cell inhibition: MSC-mediated apoptosis of activated T cells and also implicates indoleamine 2,3-dioxygenase.
45. Maccario R, Podesta M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90:516-525.
46. Glennie S, Soeiro I, Dyson PJ, et al. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005; 105:2821-2827. Elegant study refines mechanisms of inhibition which extend to B cells.
47. Beyth S, Borovsky Z, Mevorach D, et al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005; 105:2214-2219.
48. Kang HS, Chan J, Abavana C, et al. A paradoxical role for IFN-gamma in the immune properties of mesenchymal stem cells during viral challenge. Exp Hematol 2005; 33:796-803.
49. Zhang W, Ge W, Li C, et al. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 2004; 13:263-271.
50. Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107:367-372. Mechanism for B-cell modulation by MSCs.
51. Chung NG, Jeong DC, Park SJ, et al. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation. Int J Hematol 2006; 80:370-376.
52. Sudres M, Norol F, Trenado A, et al. Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol 2006; 176:7761-7767. MSCs do not prevent GVHD in mice undergoing allomismatched transplants.
53. Li A, Zhang Q, Jiang J, et al. Co-transplantation of bone marrow stromal cells transduced with IL-7 gene enhances immune reconstitution after allogeneic bone marrow transplantation in mice. Gene Ther 2006; 13:1178-1187.
54. Lee ST, Jang JH, Cheong JW, et al. Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by coinfusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype. Br J Haematol 2002; 118:1128-1131.
55. Lazarus H, Koc O, Devine S, 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; 11:389-398.
56. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363:1439-1441.
57. Koc ON, Day J, Neider M, et al. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 2002; 30:215-222.
58. Horwitz EM, Gordon PL, Koo WKK, 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 USA 2002; 99:8932-8937.
59. Pochampally RR, Horwitz EM, DiGirolamo CM, et al. Correction of a mineralization defect by overexpression of a wild-type cDNA for COL1A1 in marrow stromal cells (MSCs) from a patient with osteogenesis imperfecta: a strategy for rescuing mutations that produce dominant-negative protein defects. Gene Therapy 2005; 12:1119-1125.
60. Dantzer D, Ferguson P, Hill RP, et al. Effect of radiation and cell implantation on wound healing in a rat model. J Surg Oncol 2003; 83:185-190.
61. Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Resp Cell Mol Biol 2005; 33:145-152.
62. Mansilla E, Marin GH, Sturla F, et al. Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplant Proc 2005; 37:292-294.
63. Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 2003; 9:1195-1201.
64. Berry MF, Engler AJ, Woo J, et al. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Heart Circ Physiol 2006; 290:2196-2203.
65. Gnecchi M, He H, Noiseux N, et al. Evidence supporting paracine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB 2006; 20:661-669. MSCs may help to repair myocardium by a paracrine mechanism rather than by transdifferentiation to cardiomyocytes.
66. Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogenic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci USA 2005; 102:11474-11479. A suitable animal model for a clinical trial.
67. Miyahara Y, Nagaya N, Kataoka M, et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 2006; 12:459-465.