Rethinking regenerative medicine: A macrophage-centered approach

Frontiers in Immunology

Volumn 5, Issue NOV, 2014, Pages

  Brown, Bryan N ^a,b   Sicari, Brian M ^a,c   Badylak, Stephen F ^a,c  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b University of Pittsburgh   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

Biomaterials; Foreign body reaction; Host response; Macrophages; Regenerative medicine; Stem cells

Indexed keywords

GAMMA INTERFERON; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 4; PROTEINASE; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA;

CELL ACTIVITY; CELL DIFFERENTIATION; CELL MIGRATION; CELL POLARITY; CELL PROLIFERATION; CELL THERAPY; EXTRACELLULAR MATRIX; FOREIGN BODY REACTION; IMMUNE RESPONSE; IMMUNOMODULATION; M1 MACROPHAGE; M2 MACROPHAGE; MACROPHAGE; MACROPHAGE ACTIVATION; MACROPHAGE POLARIZATION; MUSCLE INJURY; MUSCLE REGENERATION; NONHUMAN; PHENOTYPE; REGENERATIVE MEDICINE; REVIEW; SKELETAL MUSCLE; TISSUE ENGINEERING; TISSUE SCAFFOLD; WOUND HEALING;

EID: 84919435543     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00510     Document Type: Review

References (149)

1. Adamson R. Role of macrophages in normal wound healing: an overview. J Wound Care (2009) 18(8):349-51. doi: 10.12968/jowc.2009.18.8.43636
2. Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med (2011) 13:e23. doi:10.1017/S1462399411001943
3. Brown BN, Londono R, Tottey S, Zhang L, Kukla KA, Wolf MT, et al. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater (2012) 8(3):978-87. doi:10.1016/j.actbio.2011.11.031
4. Deng B, Wehling-Henricks M, Villalta SA, Wang Y, Tidball JG. IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. J Immunol (2012) 189(7):3669-80. doi:10.4049/jimmunol.1103180
5. Longbrake EE, Lai W, Ankeny DP, Popovich PG. Characterization and modeling of monocyte-derived macrophages after spinal cord injury. J Neurochem (2007) 102(4):1083-94. doi:10.1111/j.1471-4159.2007.04617.x
6. Novak ML, Koh TJ. Macrophage phenotypes during tissue repair. J Leukoc Biol (2013) 93(6):875-81. doi:10.1189/jlb.1012512
7. Ruffell D, Mourkioti F, Gambardella A, Kirstetter P, Lopez RG, Rosenthal N, et al. A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair. Proc Natl Acad Sci U S A (2009) 106(41):17475-80. doi:10.1073/pnas.0908641106
8. Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, et al. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity (2013) 38(3):555-69. doi:10.1016/j.immuni.2013.02.012
9. Albina JE, Mills CD, Henry WL Jr, Caldwell MD. Temporal expression of different pathways of 1-arginine metabolism in healing wounds. J Immunol (1990) 144(10):3877-80.
10. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol (2000) 164(12):6166-73. doi:10.4049/jimmunol.164.12.6166
11. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol (2002) 23(11):549-55. doi:10.1016/S1471-4906(02)02302-5
12. Mills CD. M1 and M2 macrophages: oracles of health and disease. Crit Rev Immunol (2012) 32(6):463-88. doi:10.1615/CritRevImmunol.v32.i6.10
13. Mills CD, Shearer J, Evans R, Caldwell MD. Macrophage arginine metabolism and the inhibition or stimulation of cancer. J Immunol (1992) 149(8):2709-14.
14. Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials (2012) 33(15):3792-802. doi:10.1016/j.biomaterials.2012.02.034
15. Capobianco A, Rovere-Querini P. Endometriosis, a disease of the macrophage. Front Immunol (2013) 4:9. doi:10.3389/fimmu.2013.00009
16. Pechkovsky DV, Prasse A, Kollert F, Engel KM, Dentler J, Luttmann W, et al. Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction. Clin Immunol (2010) 137(1):89-101. doi:10.1016/j.clim.2010.06.017
17. Smith KA, Pearson CB, Hachey AM, Xia DL, Wachtman LM. Alternative activation of macrophages in rhesus macaques (Macaca mulatta) with endometriosis. Comp Med (2012) 62(4):303-10.
18. Stoger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, et al. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis (2012) 225(2):461-8. doi:10.1016/j.atherosclerosis.2012.09.013
19. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol (2009) 9(4):259-70. doi:10.1038/nri2528
20. Godwin JW, Pinto AR, Rosenthal NA. Macrophages are required for adult salamander limb regeneration. Proc Natl Acad Sci U S A (2013) 110(23):9415-20. doi:10.1073/pnas.1300290110
21. Li L, Yan B, Shi YQ, Zhang WQ, Wen ZL. Live imaging reveals differing roles of macrophages and neutrophils during zebrafish tail fin regeneration. J Biol Chem (2012) 287(30):25353-60. doi:10.1074/jbc. M112.349126
22. Godwin JW, Rosenthal N. Scar-free wound healing and regeneration in amphibians: immunological influences on regenerative success. Differentiation (2014) 87(1-2):66-75. doi:10.1016/j.diff.2014.02.002
23. Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature (2013) 496(7446):445-55. doi:10.1038/nature12034
24. Mauro A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol (1961) 9:493-5. doi:10.1083/jcb.9.2.493
25. Muir AR, Kanji AH, Allbrook D. The structure of the satellite cells in skeletal muscle. J Anat (1965) 99(Pt 3):435-44.
26. Wozniak AC, Kong J, Bock E, Pilipowicz O, Anderson JE. Signaling satellite-cell activation in skeletal muscle: markers, models, stretch, and potential alternate pathways. Muscle Nerve (2005) 31(3):283-300. doi:10.1002/mus.20263
27. Zammit PS, Partridge TA, Yablonka-Reuveni Z. The skeletal muscle satellite cell: the stem cell that came in from the cold. J Histochem Cytochem (2006) 54(11):1177-91. doi:10.1369/jhc.6R6995.2006
28. Hawke TJ, Garry DJ. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol (2001) 91(2):534-51.
29. Charge SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev (2004) 84(1):209-38. doi:10.1152/physrev.00019.2003
30. Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol (2010) 298(5):R1173-87. doi:10.1152/ajpregu.00735.2009
31. Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N, Plonquet A, et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med (2007) 204(5):1057-69. doi:10.1084/jem.20070075
32. Bondesen BA, Mills ST, Pavlath GK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am J Physiol Cell Physiol (2006) 290(6):C1651-9. doi:10.1152/ajpcell.00518.2005
33. Contreras-Shannon V, Ochoa O, Reyes-Reyna SM, Sun D, Michalek JE, Kuziel WA, et al. Fat accumulation with altered inflammation and regeneration in skeletal muscle of CCR2-/- mice following ischemic injury. Am J Physiol Cell Physiol (2007) 292(2):C953-67. doi:10.1152/ajpcell.00154.2006
34. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science (2009) 325(5940):612-6. doi:10.1126/science.1175202
35. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol (2005) 288(2):R345-53. doi:10.1152/ajpregu.00454.2004
36. St Pierre BA, Tidball JG. Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension. J Appl Physiol (1994) 77(1):290-7.
37. McLennan IS. Degenerating and regenerating skeletal muscles contain several subpopulations of macrophages with distinct spatial and temporal distributions. J Anat (1996) 188(Pt 1):17-28.
38. Villalta SA, Nguyen HX, Deng B, Gotoh T, Tidball JG. Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet (2009) 18(3):482-96. doi:10.1093/hmg/ddn376
39. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol (2005) 5(12):953-64. doi:10.1038/nri1733
40. Cohen HB, Mosser DM. Extrinsic and intrinsic control of macrophage inflammatory responses. J Leukoc Biol (2013) 94(5):913-9. doi:10.1189/jlb.0413236
41. Liu D, Sartor MA, Nader GA, Gutmann L, Treutelaar MK, Pistilli EE, et al. Skeletal muscle gene expression in response to resistance exercise: sex specific regulation. BMC Genomics (2010) 11:659. doi:10.1186/1471-2164-11-659
42. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest (1998) 101(4):890-8.
43. Sicari BM, Dziki JL, Siu BF, Medberry CJ, Dearth CL, Badylak SF. The promotion of a constructive macrophage phenotype by solubilized extracellular matrix. Biomaterials (2014) 35(30):8605-12. doi:10.1016/j.biomaterials.2014.06.060
44. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity (2010) 32(5):593-604. doi:10.1016/j.immuni.2010.05.007
45. Gordon S. Alternative activation of macrophages. Nat Rev Immunol (2003) 3(1):23-35. doi:10.1038/nri978
46. Collins RA, Grounds MD. The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice. J Histochem Cytochem (2001) 49(8):989-1001. doi:10.1177/002215540104900807
47. Zador E, Mendler L, Takacs V, de Bleecker J, Wuytack F. Regenerating soleus and extensor digitorum longus muscles of the rat show elevated levels of TNF-alpha and its receptors, TNFR-60 and TNFR-80. Muscle Nerve (2001) 24(8):1058-67. doi:10.1002/mus.110
48. Li YP. TNF-alpha is a mitogen in skeletal muscle. Am J Physiol Cell Physiol (2003) 285(2):C370-6. doi:10.1152/ajpcell.00453.2002
49. Teixeira CF, Zamuner SR, Zuliani JP, Fernandes CM, Cruz-Hofling MA, Fernandes I, et al. Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom. Muscle Nerve (2003) 28(4):449-59. doi:10.1002/mus.10453
50. Chen SE, Gerken E, Zhang Y, Zhan M, Mohan RK, Li AS, et al. Role of TNF-{alpha} signaling in regeneration of cardiotoxin-injured muscle. Am J Physiol Cell Physiol (2005) 289(5):C1179-87. doi:10.1152/ajpcell.00062.2005
51. Warren GL, Hulderman T, Jensen N, McKinstry M, Mishra M, Luster MI, et al. Physiological role of tumor necrosis factor alpha in traumatic muscle injury. FASEB J (2002) 16(12):1630-2. doi:10.1096/fj.02-0187fje
52. Langen RC, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. FASEB J (2001) 15(7):1169-80. doi:10.1096/fj.00-0463
53. Langen RC, Van Der Velden JL, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization. FASEB J (2004) 18(2):227-37. doi:10.1096/fj.03-0251com
54. Langen RC, Schols AM, Kelders MC, van der Velden JL, Wouters EF, Janssen-Heininger YM. Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation. Am J Respir Cell Mol Biol (2006) 35(6):689-96. doi:10.1165/rcmb.2006-0103OC
55. Tidball JG, Wehling-Henricks M. Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol (2007) 578(Pt 1):327-36. doi:10.1113/jphysiol.2006.118265
56. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med (1999) 341(10):738-46. doi:10.1056/NEJM199909023411006
57. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature (2008) 453(7193):314-21. doi:10.1038/nature07039
58. Huebener P, Schwabe RF. Regulation of wound healing and organ fibrosis by toll-like receptors. Biochim Biophys Acta (2013) 1832(7):1005-17. doi:10.1016/j.bbadis.2012.11.017
59. Galli SJ, Borregaard N, Wynn TA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol (2011) 12(11):1035-44. doi:10.1038/ni.2109
60. Sindrilaru A, Scharffetter-Kochanek K. Disclosure of the culprits: macrophages-versatile regulators of wound healing. Adv Wound Care (New Rochelle) (2013) 2(7):357-68. doi:10.1089/wound.2012.0407
61. Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol (2012) 180(4):1340-55. doi:10.1016/j.ajpath.2012.02.004
62. Stout RD. Editorial: macrophage functional phenotypes: no alternatives in dermal wound healing? J Leukoc Biol (2010) 87(1):19-21. doi:10.1189/jlb.0509311
63. Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Muller W, et al. Differential roles of macrophages in diverse phases of skin repair. J Immunol (2010) 184(7):3964-77. doi:10.4049/jimmunol.0903356
64. Brancato SK, Albina JE. Wound macrophages as key regulators of repair: origin, phenotype, and function. Am J Pathol (2011) 178(1):19-25. doi:10.1016/j.ajpath.2010.08.003
65. Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest (2011) 121(3):985-97. doi:10.1172/JCI44490
66. Mirza R, DiPietro LA, Koh TJ. Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol (2009) 175(6):2454-62. doi:10.2353/ajpath.2009.090248
67. Mirza R, Koh TJ. Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine (2011) 56(2):256-64. doi:10.1016/j.cyto.2011.06.016
68. Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One (2010) 5(3):e9539. doi:10.1371/journal.pone.0009539
69. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci (2005) 8(6):752-8. doi:10.1038/nn1472
70. Hines DJ, Hines RM, Mulligan SJ, Macvicar BA. Microglia processes block the spread of damage in the brain and require functional chloride channels. Glia (2009) 57(15):1610-8. doi:10.1002/glia.20874
71. Pineau I, Lacroix S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol (2007) 500(2):267-85. doi:10.1002/cne.21149
72. Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine (2004) 29(9):966-71. doi:10.1097/00007632-200405010-00004
73. Yang L, Jones NR, Blumbergs PC, Van Den Heuvel C, Moore EJ, Manavis J, et al. Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat. J Clin Neurosci (2005) 12(3):276-84. doi:10.1016/j.jocn.2004.06.011
74. Schwartz M. "Tissue-repairing" blood-derived macrophages are essential for healing of the injured spinal cord: from skin-activated macrophages to infiltrating blood-derived cells? Brain Behav Immun (2010) 24(7):1054-7. doi:10.1016/j.bbi.2010.01.010
75. Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med (2009) 6(7):e1000113. doi:10.1371/journal.pmed.1000113
76. Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci (2013) 16(9):1211-8. doi:10.1038/nn.3469
77. Anderson JM. Inflammatory response to implants. ASAIO Trans (1988) 34(2):101-7. doi:10.1097/00002480-198804000-00005
78. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol (2008) 20(2):86-100. doi:10.1016/j.smim.2007.11.004
79. Dadsetan M, Jones JA, Hiltner A, Anderson JM. Surface chemistry mediates adhesive structure, cytoskeletal organization, and fusion of macrophages. J Biomed Mater Res A (2004) 71(3):439-48. doi:10.1002/jbm.a.30165
80. Henson PM. The immunologic release of constituents from neutrophil leukocytes. II. Mechanisms of release during phagocytosis, and adherence to nonphagocytosable surfaces. J Immunol (1971) 107(6):1547-57.
81. Hernandez-Pando R, Bornstein QL, Aguilar Leon D, Orozco EH, Madrigal VK, Martinez Cordero E. Inflammatory cytokine production by immunological and foreign body multinucleated giant cells. Immunology (2000) 100(3):352-8. doi:10.1046/j.1365-2567.2000.00025.x
82. Kovacs EJ. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today (1991) 12(1):17-23. doi:10.1016/0167-5699(91)90107-5
83. Williams GT, Williams WJ. Granulomatous inflammation - a review. J Clin Pathol (1983) 36(7):723-33. doi:10.1136/jcp.36.7.723
84. Ratner BD. The biocompatibility manifesto: biocompatibility for the twenty-first century. J Cardiovasc Transl Res (2011) 4(5):523-7. doi:10.1007/s12265-011-9287-x
85. Williams DF. On the mechanisms of biocompatibility. Biomaterials (2008) 29(20):2941-53. doi:10.1016/j.biomaterials.2008.04.023
86. Brown BN, Badylak SF. Expanded applications, shifting paradigms and an improved understanding of host-biomaterial interactions. Acta Biomater (2013) 9(2):4948-55. doi:10.1016/j.actbio.2012.10.025
87. Badylak SF, Brown BN, Gilbert TW, Daly KA, Huber A, Turner NJ. Biologic scaffolds for constructive tissue remodeling. Biomaterials (2011) 32(1):316-9. doi:10.1016/j.biomaterials.2010.09.018
88. Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res (2014) 163(4):268-85. doi:10.1016/j.trsl.2013.11.003
89. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials (2011) 32(12):3233-43. doi:10.1016/j.biomaterials.2011.01.057
90. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials (2006) 27(19):3675-83. doi:10.1016/j.biomaterials.2006.02.014
91. Valentin JE, Badylak JS, McCabe GP, Badylak SF. Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. J Bone Joint Surg Am (2006) 88(12):2673-86. doi:10.2106/JBJS.E.01008
92. Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A (2008) 14(11):1835-42. doi:10.1089/ten.tea.2007.0264
93. Brown BN, Valentin JE, Stewart-Akers AM, McCabe GP, Badylak SF. Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials (2009) 30(8):1482-91. doi:10.1016/j.biomaterials.2008.11.040
94. Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med (2003) 9(6):702-12. doi:10.1038/nm0603-702
95. Urish KL, Vella JB, Okada M, Deasy BM, Tobita K, Keller BB, et al. Antioxidant levels represent a major determinant in the regenerative capacity of muscle stem cells. Mol Biol Cell (2009) 20(1):509-20. doi:10.1091/mbc. E08-03-0274
96. Guerette B, Asselin I, Skuk D, Entman M, Tremblay JP. Control of inflammatory damage by anti-LFA-1: increase success of myoblast transplantation. Cell Transplant (1997) 6(2):101-7. doi:10.1016/S0963-6897(96)00230-8
97. Huard J, Acsadi G, Jani A, Massie B, Karpati G. Gene transfer into skeletal muscles by isogenic myoblasts. Hum Gene Ther (1994) 5(8):949-58. doi:10.1089/hum.1994.5.8-949
98. Fan Y, Maley M, Beilharz M, Grounds M. Rapid death of injected myoblasts in myoblast transfer therapy. Muscle Nerve (1996) 19(7):853-60. doi:10.1002/(SICI)1097-4598(199607)19:7<853::AID-MUS7>3.0.CO;2-8
99. Camargo FD, Chambers SM, Drew E, McNagny KM, Goodell MA. Hematopoietic stem cells do not engraft with absolute efficiencies. Blood (2006) 107(2):501-7. doi:10.1182/blood-2005-02-0655
100. Glimm H, Oh IH, Eaves CJ. Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G(2)/M transit and do not reenter G(0). Blood (2000) 96(13):4185-93.
101. Sicari BM, Dearth CL, Badylak SF. Tissue engineering and regenerative medicine approaches to enhance the functional response to skeletal muscle injury. Anat Rec (2014) 297(1):51-64. doi:10.1002/ar.22794
102. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med (2005) 11(4):367-8. doi:10.1038/nm0405-367
103. Murry CE, Reinecke H, Pabon LM. Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol (2006) 47(9):1777-85. doi:10.1016/j.jacc.2006.02.002
104. Gharaibeh B, Lavasani M, Cummins JH, Huard J. Terminal differentiation is not a major determinant for the success of stem cell therapy - cross-talk between muscle-derived stem cells and host cells. Stem Cell Res Ther (2011) 2(4):31. doi:10.1186/scrt72
105. Perez-Ilzarbe M, Agbulut O, Pelacho B, Ciorba C, San Jose-Eneriz E, Desnos M, et al. Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium. Eur J Heart Fail (2008) 10(11):1065-72. doi:10.1016/j.ejheart.2008.08.002
106. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res (2008) 103(11):1204-19. doi:10.1161/CIRCRESAHA.108.176826
107. Arthur A, Zannettino A, Gronthos S. The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair. J Cell Physiol (2009) 218(2):237-45. doi:10.1002/jcp.21592
108. Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med (2007) 262(5):509-25. doi:10.1111/j.1365-2796.2007.01844.x
109. Le Blanc K. Mesenchymal stromal cells: tissue repair and immune modulation. Cytotherapy (2006) 8(6):559-61. doi:10.1080/14653240601045399
110. Le Blanc K. Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy (2003) 5(6):485-9. doi:10.1080/14653240310003611
111. Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol (2009) 37(12):1445-53. doi:10.1016/j.exphem.2009.09.004
112. Eggenhofer E, Hoogduijn MJ. Mesenchymal stem cell-educated macrophages. Trans Res (2012) 1(1):12. doi:10.1186/2047-1440-1-12
113. Gao S, Mao F, Zhang B, Zhang L, Zhang X, Wang M, et al. Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-kappaB and signal transducer and activator of transcription 3 pathways. Exp Biol Med (2014) 239(3):366-75. doi:10.1177/1535370213518169
114. Nakajima H, Uchida K, Guerrero AR, Watanabe S, Sugita D, Takeura N, et al. Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. J Neurotrauma (2012) 29(8):1614-25. doi:10.1089/neu.2011.2109
115. Walker PA, Bedi SS, Shah SK, Jimenez F, Xue H, Hamilton JA, et al. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. J Neuroinflammation (2012) 9:228. doi:10.1186/1742-2094-9-228
116. Dayan V, Yannarelli G, Billia F, Filomeno P, Wang XH, Davies JE, et al. Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction. Basic Res Cardiol (2011) 106(6):1299-310. doi:10.1007/s00395-011-0221-9
117. Yannarelli G, Dayan V, Pacienza N, Lee CJ, Medin J, Keating A. Human umbilical cord perivascular cells exhibit enhanced cardiomyocyte reprogramming and cardiac function after experimental acute myocardial infarction. Cell Transplant (2013) 22(9):1651-66. doi:10.3727/096368912X657675
118. Adutler-Lieber S, Ben-Mordechai T, Naftali-Shani N, Asher E, Loberman D, Raanani E, et al. Human macrophage regulation via interaction with cardiac adipose tissue-derived mesenchymal stromal cells. J Cardiovasc Pharmacol Ther (2013) 18(1):78-86. doi:10.1177/1074248412453875
119. Wise AF, Williams TM, Kiewiet MB, Payne NL, Siatskas C, Samuel CS, et al. Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury. Am J Physiol Renal Physiol (2014) 306(10):F1222-35. doi:10.1152/ajprenal.00675.2013
120. Geng Y, Zhang L, Fu B, Zhang J, Hong Q, Hu J, et al. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages. Stem Cell Res Ther (2014) 5(3):80. doi:10.1186/scrt469
121. Song X, Xie S, Lu K, Wang C. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages. Inflammation (2014). doi:10.1007/s10753-014-9954-6
122. Brodbeck WG, Anderson JM. Giant cell formation and function. Curr Opin Hematol (2009) 16(1):53-7. doi:10.1097/MOH.0b013e32831ac52e
123. Wolf MT, Dearth CL, Ranallo CA, LoPresti ST, Carey LE, Daly KA, et al. Macrophage polarization in response to ECM coated polypropylene mesh. Biomaterials (2014) 35(25):6838-49. doi:10.1016/j.biomaterials.2014.04.115
124. Faulk DM, Londono R, Wolf MT, Ranallo CA, Carruthers CA, Wildemann JD, et al. ECM hydrogel coating mitigates the chronic inflammatory response to polypropylene mesh. Biomaterials (2014) 35(30):8585-95. doi:10.1016/j.biomaterials.2014.06.057
125. Wolf MT, Vodovotz Y, Tottey S, Brown BN, Badylak SF. Predicting in vivo responses to biomaterials via combined in vitro and in silico analysis. Tissue Eng Part C Methods (2014). doi:10.1089/ten.tec.2014.0167
126. Saino E, Focarete ML, Gualandi C, Emanuele E, Cornaglia AI, Imbriani M, et al. Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines. Biomacromolecules (2011) 12(5):1900-11. doi:10.1021/bm200248h
127. Garg K, Pullen NA, Oskeritzian CA, Ryan JJ, Bowlin GL. Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials (2013) 34(18):4439-51. doi:10.1016/j.biomaterials.2013.02.065
128. Sussman EM, Halpin MC, Muster J, Moon RT, Ratner BD. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann Biomed Eng (2014) 42(7):1508-16. doi:10.1007/s10439-013-0933-0
129. Bota PC, Collie AM, Puolakkainen P, Vernon RB, Sage EH, Ratner BD, et al. Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro. J Biomed Mater Res A (2010) 95(2):649-57. doi:10.1002/jbm.a.32893
130. Fukano Y, Usui ML, Underwood RA, Isenhath S, Marshall AJ, Hauch KD, et al. Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice. J Biomed Mater Res A (2010) 94(4):1172-86. doi:10.1002/jbm.a.32798
131. Madden LR, Mortisen DJ, Sussman EM, Dupras SK, Fugate JA, Cuy JL, et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc Natl Acad Sci U S A (2010) 107(34):15211-6. doi:10.1073/pnas.1006442107
132. Mokarram N, Merchant A, Mukhatyar V, Patel G, Bellamkonda RV. Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials (2012) 33(34):8793-801. doi:10.1016/j.biomaterials.2012.08.050
133. Badylak SF. Regenerative medicine and developmental biology: the role of the extracellular matrix. Anat Rec B New Anat (2005) 287(1):36-41. doi:10.1002/ar.b.20081
134. Badylak SF. The extracellular matrix as a biologic scaffold material. Biomaterials (2007) 28(25):3587-93. doi:10.1016/j.biomaterials.2007.04.043
135. Badylak SF. Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response. Ann Biomed Eng (2014) 42(7):1517-27. doi:10.1007/s10439-013-0963-7
136. Badylak SF, Vorp DA, Spievack AR, Simmons-Byrd A, Hanke J, Freytes DO, et al. Esophageal reconstruction with ECM and muscle tissue in a dog model. J Surg Res (2005) 128(1):87-97. doi:10.1016/j.jss.2005.03.002
137. Sicari BM, Rubin JP, Dearth CL, Wolf MT, Ambrosio F, Boninger M, et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci Transl Med (2014) 6(234):234ra58. doi:10.1126/scitranslmed.3008085
138. Gilbert TW. Strategies for tissue and organ decellularization. J Cell Biochem (2012) 113(7):2217-22. doi:10.1002/jcb.24130
139. Keane TJ, Londono R, Turner NJ, Badylak SF. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials (2012) 33(6):1771-81. doi:10.1016/j.biomaterials.2011.10.054
140. Freytes DO, Martin J, Velankar SS, Lee AS, Badylak SF. Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix. Biomaterials (2008) 29(11):1630-7. doi:10.1016/j.biomaterials.2007.12.014
141. Wolf MT, Daly KA, Brennan-Pierce EP, Johnson SA, Carruthers CA, D'Amore A, et al. A hydrogel derived from decellularized dermal extracellular matrix. Biomaterials (2012) 33(29):7028-38. doi:10.1016/j.biomaterials.2012.06.051
142. Wolf MT, Carruthers CA, Dearth CL, Crapo PM, Huber A, Burnsed OA, et al. Polypropylene surgical mesh coated with extracellular matrix mitigates the host foreign body response. J Biomed Mater Res A (2014) 102A(1):234-46. doi:10.1002/jbm.a.34671
143. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity (2014) 41(1):14-20. doi:10.1016/j.immuni.2014.06.008
144. Ginhoux F, Lim S, Hoeffel G, Low D, Huber T. Origin and differentiation of microglia. Front Cell Neurosci (2013) 7:45. doi:10.3389/fncel.2013.00045
145. Prinz M, Tay TL, Wolf Y, Jung S. Microglia: unique and common features with other tissue macrophages. Acta Neuropathol (2014) 128(3):319-31. doi:10.1007/s00401-014-1267-1
146. Prinz M, Priller J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci (2014) 15(5):300-12. doi:10.1038/nrn3722
147. Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol (2013) 14(10):986-95. doi:10.1038/ni.2705
148. Akira S, Misawa T, Satoh T, Saitoh T. Macrophages control innate inflammation. Diabetes Obes Metab (2013) 15(Suppl 3):10-8. doi:10.1111/dom.12151
149. Mahbub S, Deburghgraeve CR, Kovacs EJ. Advanced age impairs macrophage polarization. J Interferon Cytokine Res (2012) 32(1):18-26. doi:10.1089/jir.2011.0058