Abstract
When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field.When a sheep loses its tail, it cannot regenerate it in the manner of lizards. On the other hand, it is possible to clone mammals from somatic cells, showing that a complete developmental program is intact in a wounded sheep's tail the same way it is in a lizard. Thus, there is a requirement for more than only the presence of the entire genetic code in somatic cells for regenerative abilities. Thoughts like this have motivated us to assemble more than just a factographic synopsis on tissue regeneration. As a model, we review skin wound healing in chronological order, and when possible, we use that overview as a framework to point out possible mechanisms of how damaged tissues can restore their original structure. This article postulates the existence of tissue structural memory as a complex distributed homeostatic mechanism. We support such an idea by referring to an extremely fragmented literature base, trying to synthesize a broad picture of important principles of how tissues and organs may store information about their own structure for the purposes of regeneration. Selected developmental, surgical, and tissue engineering aspects are presented and discussed in the light of recent findings in the field.
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Abbreviations
- ECM:
-
extracellular matrix
- ESC:
-
embryonic stem cell
- FGF:
-
fibroblast growth factor
- PMN:
-
polymorphonuclear neutrophils
References
Fathke C, Wilson L, Shah K, Kim B, Hocking A, Moon R, Isik F 2006 Wnt signaling induces epithelial differentiation during cutaneous wound healing. BMC Cell Biol 7: 4
Gilbert SF 2003 Developmental Biology. Sinauer Associates, Inc, Sunderland, pp 1–838
Li WY, Huang EY, Dudas M, Kaartinen V, Warburton D, Tuan TL 2006 Transforming growth factor-beta3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction. Wound Repair Regen 14: 516–525
Lorenz HP, Longaker MT 2003 In utero surgery for cleft lip/palate: minimizing the “Ripple Effect” of scarring. J Craniofac Surg 14: 504–511
Yannas IV, Kwan MD, Longaker MT 2007 Early fetal healing as a model for adult organ regeneration. Tissue Eng 13: 1789–1798
Dudas M, Li WY, Kim J, Yang A, Kaartinen V 2007 Palatal fusion—where do the midline cells go? A review on cleft palate, a major human birth defect. Acta Histochem 109: 1–14
Takigawa T, Shiota K 2004 Terminal differentiation of palatal medial edge epithelial cells in vitro is not necessarily dependent on palatal shelf contact and midline epithelial seam formation. Int J Dev Biol 48: 307–317
Brown NL, Sandy JR 2007 Tails of the unexpected: palatal medial edge epithelium is no more specialized than other embryonic epithelium. Orthod Craniofac Res 10: 22–35
Ahmed S, Liu CC, Nawshad A 2007 Mechanisms of palatal epithelial seam disintegration by transforming growth factor (TGF) beta3. Dev Biol 309: 193–207
Dudas M, Nagy A, Laping NJ, Moustakas A, Kaartinen V 2004 Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway. Dev Biol 266: 96–108
Dudas M, Kim J, Li WY, Nagy A, Larsson J, Karlsson S, Chai Y, Kaartinen V 2006 Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion. Dev Biol 296: 298–314
Kryger ZB, Sisco M, Roy NK, Lu L, Rosenberg D, Mustoe TA 2007 Temporal expression of the transforming growth factor-Beta pathway in the rabbit ear model of wound healing and scarring. J Am Coll Surg 205: 78–88
Cabrera RC, Siebert JW, Eidelman Y, Gold LI, Longaker MT, Garg HG 1995 The in vivo effect of hyaluronan associated protein-collagen complex on wound repair. Biochem Mol Biol Int 37: 151–158
Prime SS, Pring M, Davies M, Paterson IC 2004 TGF-beta signal transduction in oro-facial health and non-malignant disease (part I). Crit Rev Oral Biol Med 15: 324–336
Dudas M, Kaartinen V 2005 Tgf-beta superfamily and mouse craniofacial development: interplay of morphogenetic proteins and receptor signaling controls normal formation of the face. Curr Top Dev Biol 66: 65–133
Ferguson MW, O'Kane S 2004 Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci 359: 839–850
Drahovsky P, Dankovcik J, Bodnarova A, Drahovska I, Sabovcik R 1999 [Congenital diaphragmatic hernia manifesting after the neonatal period]. Rozhl Chir 78: 123–126
Xu H, Baldini A 2007 Genetic pathways to mammalian heart development: recent progress from manipulation of the mouse genome. Semin Cell Dev Biol 18: 77–83
van Wijk B, Moorman AF, van den Hoff MJ 2007 Role of bone morphogenetic proteins in cardiac differentiation. Cardiovasc Res 74: 244–255
Park C, Lavine K, Mishina Y, Deng CX, Ornitz DM, Choi K 2006 Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Development 133: 3473–3484
McLean SE, Mecham BH, Kelleher CM, Mariani TJ, Mecham RP 2005 Extracellular matrix gene expression in the developing mouse aorta. In: Wassarman P, Miner J (eds) Advances in Developmental Biology 15, Extracellular Matrix in Development and Disease. Elsevier, Amsterdam, pp 81–128
Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu MM, Du K, Epstein JA, Parmacek MS 2005 Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci USA 102: 8916–8921
Choi M, Stottmann RW, Yang YP, Meyers EN, Klingensmith J 2007 The bone morphogenetic protein antagonist noggin regulates mammalian cardiac morphogenesis. Circ Res 100: 220–228
Ma L, Lu MF, Schwartz RJ, Martin JF 2005 Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development 132: 5601–5611
Mercado-Pimentel ME, Runyan RB 2007 Multiple transforming growth factor-beta isoforms and receptors function during epithelial-mesenchymal cell transformation in the embryonic heart. Cells Tissues Organs 185: 146–156
De Coster PJ, Mortier G, Marks LA, Martens LC 2007 Cranial suture biology and dental development: genetic and clinical perspectives. J Oral Pathol Med 36: 447–455
Jiang R, Bush JO, Lidral AC 2006 Development of the upper lip: morphogenetic and molecular mechanisms. Dev Dyn 235: 1152–1166
Ingraham CR, Kinoshita A, Kondo S, Yang B, Sajan S, Trout KJ, Malik MI, Dunnwald M, Goudy SL, Lovett M, Murray JC, Schutte BC 2006 Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet 38: 1335–1340
Liu W, Sun X, Braut A, Mishina Y, Behringer RR, Mina M, Martin JF 2005 Distinct functions for Bmp signaling in lip and palate fusion in mice. Development 132: 1453–1461
Warner DR, Horn KH, Mudd L, Webb CL, Greene RM, Pisano MM 2007 PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue. Biochim Biophys Acta 1773: 814–820
Rice DP 2005 Craniofacial anomalies: from development to molecular pathogenesis. Curr Mol Med 5: 699–722
Depew MJ, Simpson CA 2006 21st century neontology and the comparative development of the vertebrate skull. Dev Dyn 235: 1256–1291
Havens BA, Rodgers B, Mina M 2006 Tissue-specific expression of Fgfr2b and Fgfr2c isoforms, Fgf10 and Fgf9 in the developing chick mandible. Arch Oral Biol 51: 134–145
Mukhopadhyay P, Greene RM, Pisano MM 2006 Expression profiling of transforming growth factor beta superfamily genes in developing orofacial tissue. Birth Defects Res A Clin Mol Teratol 76: 528–543
Nie X, Luukko K, Kettunen P 2006 BMP signalling in craniofacial development. Int J Dev Biol 50: 511–521
Oka K, Oka S, Sasaki T, Ito Y, Bringas P Jr, Nonaka K, Chai Y 2007 The role of TGF-beta signaling in regulating chondrogenesis and osteogenesis during mandibular development. Dev Biol 303: 391–404
Mancini ML, Verdi JM, Conley BA, Nicola T, Spicer DB, Oxburgh LH, Vary CP 2007 Endoglin is required for myogenic differentiation potential of neural crest stem cells. Dev Biol 308: 520–533
Sommer L 2006 Growth factors regulating neural crest cell fate decisions. Adv Exp Med Biol 589: 197–205
Hogan BM, Layton JE, Pyati UJ, Nutt SL, Hayman JW, Varma S, Heath JK, Kimelman D, Lieschke GJ 2006 Specification of the primitive myeloid precursor pool requires signaling through Alk8 in Zebrafish. Curr Biol 16: 506–511
Wan M, Cao X 2005 BMP signaling in skeletal development. Biochem Biophys Res Commun 328: 651–657
Chuong CM, Cotsarelis G, Stenn K 2007 Defining hair follicles in the age of stem cell bioengineering. J Invest Dermatol 127: 2098–2100
Gibran NS, Boyce S, Greenhalgh DG 2007 Cutaneous wound healing. J Burn Care Res 28: 577–579
Macneil S 2007 Progress and opportunities for tissue-engineered skin. Nature 445: 874–880
Li J, Chen J, Kirsner R 2007 Pathophysiology of acute wound healing. Clin Dermatol 25: 9–18
Stadelmann WK, Digenis AG, Tobin GR 1998 Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg 176: 26S–38S
Clark RA 1996 The molecular and cellular biology of wound repair. Plenum Press, New York, pp 1–620
Midwood KS, Valenick LV, Hsia HC, Schwarzbauer JE 2004 Coregulation of fibronectin signaling and matrix contraction by tenascin-C and syndecan-4. Mol Biol Cell 15: 5670–5677
Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, van de Rijn M, Botstein D, Brown PO 2004 Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol 2: E7
Eming SA, Krieg T, Davidson JM 2007 Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127: 514–525
Iba Y, Shibata A, Kato M, Masukawa T 2004 Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice. Int Immunopharmacol 4: 1873–1880
Schymeinsky J, Then C, Sindrilaru A, Gerstl R, Jakus Z, Tybulewicz VL, Scharffetter-Kochanek K, Walzog B 2007 Syk-mediated translocation of PI3Kdelta to the leading edge controls lamellipodium formation and migration of leukocytes. PLoS ONE 2: e1132
Gosain A, Muthu K, Gamelli RL, DiPietro LA 2007 Norepinephrine suppresses wound macrophage phagocytic efficiency through alpha- and beta-adrenoreceptor dependent pathways. Surgery 142: 170–179
Martin P, Leibovich SJ 2005 Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15: 599–607
Schultz SS 2005 Adult stem cell application in spinal cord injury. Curr Drug Targets 6: 63–73
Borenstein JT, Weinberg EJ, Orrick BK, Sundback C, Kaazempur-Mofrad MR, Vacanti JP 2007 Microfabrication of three-dimensional engineered scaffolds. Tissue Eng 13: 1837–1844
Orwin E, Shah A, Voorhees A, Ravi V 2007 Bioreactor design for cornea tissue engineering: material-cell interactions. Acta Biomater 3: 1041–1049
Macri L, Silverstein D, Clark RA 2007 Growth factor binding to the pericellular matrix and its importance in tissue engineering. Adv Drug Deliv Rev 59: 1366–1381
Berrier AL, Yamada KM 2007 Cell-matrix adhesion. J Cell Physiol 213: 565–573
Libby P, Lee RT 2000 Matrix matters. Circulation 102: 1874–1876
Ruoslahti E, Reed JC 1994 Anchorage dependence, integrins, and apoptosis. Cell 77: 477–478
Petrigliano FA, English CS, Barba D, Esmende S, Wu BM, McAllister DR 2007 The effects of local bFGF release and uniaxial strain on cellular adaptation and gene expression in a 3D environment: implications for ligament tissue engineering. Tissue Eng 13: 2721–2731
Lee M, Chen TT, Iruela-Arispe ML, Wu BM, Dunn JC 2007 Modulation of protein delivery from modular polymer scaffolds. Biomaterials 28: 1862–1870
Sanclimens G, Shen H, Giralt E, Albericio F, Saltzman MW, Royo M 2005 Synthesis and screening of a small library of proline-based biodendrimers for use as delivery agents. Biopolymers 80: 800–814
Karp JM, Langer R 2007 Development and therapeutic applications of advanced biomaterials. Curr Opin Biotechnol 18: 454–459
Ryu W, Huang Z, Prinz FB, Goodman SB, Fasching R 2007 Biodegradable micro-osmotic pump for long-term and controlled release of basic fibroblast growth factor. J Control Release 124: 98–105
Rhee S, Grinnell F 2007 Fibroblast mechanics in 3D collagen matrices. Adv Drug Deliv Rev 59: 1299–1305
Ito K, Yamada Y, Naiki T, Ueda M 2006 Simultaneous implant placement and bone regeneration around dental implants using tissue-engineered bone with fibrin glue, mesenchymal stem cells and platelet-rich plasma. Clin Oral Implants Res 17: 579–586
Catelas I, Sese N, Wu BM, Dunn JC, Helgerson S, Tawil B 2006 Human mesenchymal stem cell proliferation and osteogenic differentiation in fibrin gels in vitro. Tissue Eng 12: 2385–2396
Yen JL, Lin SP, Chen MR, Niu DM 2006 Clinical features of Ehlers-Danlos syndrome. J Formos Med Assoc 105: 475–480
Ferdous Z, Wei VM, Iozzo RV, Hook M, Grande-Allen KJ 2007 Decorin-TGF beta interaction regulates matrix organization and mechanical characteristics of 3-D collagen matrices. J Biol Chem 282: 35887–35898
Guillot PV, Abass O, Bassett JH, Shefelbine SJ, Bou-Gharios G, Chan J, Kurata H, Williams GR, Polak J, Fisk NM 2008 Intrauterine transplantation of human fetal mesenchymal stem cells from first trimester blood repairs bone and reduces fractures in osteogenesis imperfecta mice. Blood 111: 1717–1725. Doi:10.1182/blood-2007-08-105809
Qiao B, Padilla SR, Benya PD 2005 Transforming growth factor (TGF)-beta-activated kinase 1 mimics and mediates TGF-beta-induced stimulation of type II collagen synthesis in chondrocytes independent of Col2a1 transcription and Smad3 signaling. J Biol Chem 280: 17562–17571
Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL 2007 Regulation of immature cartilage growth by IGF-I, TGF-beta1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network. Biomech Model Mechanobiol, in press. Doi:10.1007/s10237-007-0096-8
Parker WL, Finnson KW, Soe-Lin H, Knaus P, Philip A 2007 Expression and function of TbetaRII-B, a variant of the type II TGF-beta receptor, in human chondrocytes. Osteoarthritis Cartilage 15: 442–453
Moreau JL, Caccamese JF, Coletti DP, Sauk JJ, Fisher JP 2007 Tissue engineering solutions for cleft palates. J Oral Maxillofac Surg 65: 2503–2511
Israelsson C, Lewen A, Kylberg A, Usoskin D, Althini S, Lindeberg J, Deng CX, Fukuda T, Wang Y, Kaartinen V, Mishina Y, Hillered L, Ebendal T 2006 Genetically modified bone morphogenetic protein signalling alters traumatic brain injury-induced gene expression responses in the adult mouse. J Neurosci Res 84: 47–57
Breuer CK, Mettler BA, Anthony T, Sales VL, Schoen FJ, Mayer JE 2004 Application of tissue-engineering principles toward the development of a semilunar heart valve substitute. Tissue Eng 10: 1725–1736
Levi DS, Raff E, Stepan L, Liu J, Williams RJ, Moore JW, Carman G 2005 Use of a covered stent modification to produce a transcatheter valve: laboratory and animal testing. ASAIO J 51: 719–724
Hu Z, Luo F, Pan Y, Hou C, Ren L, Chen J, Wang J, Zhang Y 2007 Arg-Gly-Asp (RGD) peptide conjugated poly(lactic acid)-poly(ethylene oxide) micelle for targeted drug delivery. J Biomed Mater Res A, in press. Doi:10.1002/jbm.a.31615
Lwigale PY, Cressy PA, Bronner-Fraser M 2005 Corneal keratocytes retain neural crest progenitor cell properties. Dev Biol 288: 284–293
Warnke PH, Wiltfang J, Springer I, Acil Y, Bolte H, Kosmahl M, Russo PA, Sherry E, Lutzen U, Wolfart S, Terheyden H 2006 Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible. Biomaterials 27: 3163–3167
Wang CC, Chen CH, Lin WW, Hwang SM, Hsieh PC, Lai PH, Yeh YC, Chang Y, Sung HW 2008 Direct Intramyocardial injection of mesenchymal stem cell sheet fragments improves cardiac functions after infarction. Cardiovasc Res 77: 515–524. Doi:10.1093/cvr/cvm046
Derynck R, Akhurst RJ 2007 Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol 9: 1000–1004
Dragoo JL, Carlson G, McCormick F, Khan-Farooqi H, Zhu M, Zuk PA, Benhaim P 2007 Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Eng 13: 1615–1621
Pierret C, Spears K, Maruniak JA, Kirk MD 2006 Neural crest as the source of adult stem cells. Stem Cells Dev 15: 286–291
Perin L, Giuliani S, Jin D, Sedrakyan S, Carraro G, Habibian R, Warburton D, Atala A, De Filippo RE 2007 Renal differentiation of amniotic fluid stem cells. Cell Prolif 40: 936–948
Golubev A, Khrustalev S, Butov A 2003 An in silico investigation into the causes of telomere length heterogeneity and its implications for the Hayflick limit. J Theor Biol 225: 153–170
Blagosklonny MV 2006 Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle 5: 2087–2102
Hlinka D, Dudas M, Herman M, Kalina I 2001 Experimental attempts to extend the current preimplantation genetic diagnosis with individual karyotypization of human blastomeres. Reprod Nutr Dev 41: 91–106
Shkumatov A, Kuznyetsov V, Cieslak J, Ilkevitch Y, Verlinsky Y 2007 Obtaining metaphase spreads from single blastomeres for PGD of chromosomal rearrangements. Reprod Biomed Online 14: 498–503
Findikli N, Candan NZ, Kahraman S 2006 Human embryonic stem cell culture: current limitations and novel strategies. Reprod Biomed Online 13: 581–590
El Sherif A, Yano F, Mittal S, Filipi CJ 2006 Collagen metabolism and recurrent hiatal hernia: cause and effect?. Hernia 10: 511–520
Greenhalgh DG 1998 The role of apoptosis in wound healing. Int J Biochem Cell Biol 30: 1019–1030
Bellini A, Mattoli S 2007 The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Lab Invest 87: 858–870
Hong KM, Belperio JA, Keane MP, Burdick MD, Strieter RM 2007 Differentiation of human circulating fibrocytes as mediated by transforming growth factor-beta and peroxisome proliferator-activated receptor gamma. J Biol Chem 282: 22910–22920
Tomasek JJ, Vaughan MB, Kropp BP, Gabbiani G, Martin MD, Haaksma CJ, Hinz B 2006 Contraction of myofibroblasts in granulation tissue is dependent on Rho/Rho kinase/myosin light chain phosphatase activity. Wound Repair Regen 14: 313–320
Virag JA, Rolle ML, Reece J, Hardouin S, Feigl EO, Murry CE 2007 Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function. Am J Pathol 171: 1431–1440
Desmouliere A, Chaponnier C, Gabbiani G 2005 Tissue repair, contraction, and the myofibroblast. Wound Repair Regen 13: 7–12
Sandulache VC, Parekh A, Dohar JE, Hebda PA 2007 Fetal dermal fibroblasts retain a hyperactive migratory and contractile phenotype under 2-and 3-dimensional constraints compared to normal adult fibroblasts. Tissue Eng 13: 2791–2801
Rinn JL, Bondre C, Gladstone HB, Brown PO, Chang HY 2006 Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet 2: e119
Watterson KR, Lanning DA, Diegelmann RF, Spiegel S 2007 Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing. Wound Repair Regen 15: 607–616
Roy S, Khanna S, Rink T, Radtke J, Williams WT, Biswas S, Schnitt R, Strauch AR, Sen CK 2007 p21waf1/cip1/sdi1 as a central regulator of inducible smooth muscle actin expression and differentiation of cardiac fibroblasts to myofibroblasts. Mol Biol Cell 18: 4837–4846
Li Z, Dranoff JA, Chan EP, Uemura M, Sevigny J, Wells RG 2007 Transforming growth factor-beta and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 46: 1246–1256
Goldberg MT, Han YP, Yan C, Shaw MC, Garner WL 2007 TNF-alpha suppresses alpha-smooth muscle actin expression in human dermal fibroblasts: an implication for abnormal wound healing. J Invest Dermatol 127: 2645–2655
Dvorak HF 1986 Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315: 1650–1659
Chang HY, Cotsarelis G 2007 Turning skin into embryonic stem cells. Nat Med 13: 783–784
Farahani RM 2007 Hidden cameras for lifelong injurious stimuli: a hypothetic approach toward “wound memory”. Med Hypotheses 69: 472–473
McNulty AK, Schmidt M, Feeley T, Kieswetter K 2007 Effects of negative pressure wound therapy on fibroblast viability, chemotactic signaling, and proliferation in a provisional wound (fibrin) matrix. Wound Repair Regen 15: 838–846
Ghazarian A, Garner WL, Ehrlich HP 2000 Memory of past exposure to the chemokine IL-8 inhibits the contraction of fibroblast-populated collagen lattices. Exp Mol Pathol 69: 242–247
Karamichos D, Lakshman N, Petroll WM 2007 Regulation of corneal fibroblast morphology and collagen reorganization by extracellular matrix mechanical properties. Invest Ophthalmol Vis Sci 48: 5030–5037
Wang JH, Thampatty BP, Lin JS, Im HJ 2007 Mechanoregulation of gene expression in fibroblasts. Gene 391: 1–15
Park JS, Huang NF, Kurpinski KT, Patel S, Hsu S, Li S 2007 Mechanobiology of mesenchymal stem cells and their use in cardiovascular repair. Front Biosci 12: 5098–5116
Thiery JP, Sleeman JP 2006 Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7: 131–142
Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW 2007 Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 213: 374–383
Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A 2005 TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 16: 1987–2002
Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G 2007 Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316–320
Fu Q, Deng CL, Liu W, Cao YL 2007 Urethral replacement using epidermal cell-seeded tubular acellular bladder collagen matrix. BJU Int 99: 1162–1165
Brandner JM, Zacheja S, Houdek P, Moll I, Lobmann R 2008 Expression of matrix metalloproteinases, cytokines and connexins in diabetic and non-diabetic human keratinocytes before and after transplantation into an ex-vivo wound healing model. Diabetes Care 31: 114–120
Rimmer S, Johnson C, Zhao B, Collier J, Gilmore L, Sabnis S, Wyman P, Sammon C, Fullwood NJ, Macneil S 2007 Epithelialization of hydrogels achieved by amine functionalization and co-culture with stromal cells. Biomaterials 28: 5319–5331
Sherman RA, Shapiro CE, Yang RM 2007 Maggot therapy for problematic wounds: uncommon and off-label applications. Adv Skin Wound Care 20: 602–610
Schaden W, Thiele R, Kolpl C, Pusch M, Nissan A, Attinger CE, Maniscalco-Theberge ME, Peoples GE, Elster EA, Stojadinovic A 2007 Shock wave therapy for acute and chronic soft tissue wounds: a feasibility study. J Surg Res 143: 1–12
Chong AK, Satterwhite T, Pham HM, Costa MA, Luo J, Longaker MT, Wyss-Coray T, Chang J 2007 Live imaging of Smad2/3 signaling in mouse skin wound healing. Wound Repair Regen 15: 762–766
Askenasy N, Farkas DL 2003 In vivo imaging studies of the effect of recipient conditioning, donor cell phenotype and antigen disparity on homing of haematopoietic cells to the bone marrow. Br J Haematol 120: 505–515
Sorg H, Krueger C, Vollmar B 2007 Intravital insights in skin wound healing using the mouse dorsal skin fold chamber. J Anat 211: 810–818
Parnell LK, Ciufi B, Gokoo CF 2005 Preliminary use of a hydrogel containing enzymes in the treatment of stage II and stage III pressure ulcers. Ostomy Wound Manage 51: 50–60
Telgenhoff D, Lam K, Ramsay S, Vasquez V, Villareal K, Slusarewicz P, Attar P, Shroot B 2007 Influence of papain urea copper chlorophyllin on wound matrix remodeling. Wound Repair Regen 15: 727–735
Teot L, Lambert L, Ourabah Z, Bey E, Steenman C, Wierzbiecka E, Malikov S, Charles JP, Vives F, Bohbot S 2006 Use of topical negative pressure with a lipidocolloid dressing: results of a clinical evaluation. J Wound Care 15: 355–358
Yates CC, Whaley D, Babu R, Zhang J, Krishna P, Beckman E, Pasculle AW, Wells A 2007 The effect of multifunctional polymer-based gels on wound healing in full thickness bacteria-contaminated mouse skin wound models. Biomaterials 28: 3977–3986
Barbul A, Uliyargoli A 2007 Use of exogenous arginine in multiple organ dysfunction syndrome and sepsis. Crit Care Med 35: S564–S567
Hopf HW, Rollins MD 2007 Wounds: an overview of the role of oxygen. Antioxid Redox Signal 9: 1183–1192
Brem H, Tomic-Canic M 2007 Cellular and molecular basis of wound healing in diabetes. J Clin Invest 117: 1219–1222
Lansdown AB, Sampson B, Rowe A 2001 Experimental observations in the rat on the influence of cadmium on skin wound repair. Int J Exp Pathol 82: 35–41
Chung JH, Eun HC 2007 Angiogenesis in skin aging and photoaging. J Dermatol 34: 593–600
Kleban J, Mikes J, Szilardiova B, Koval J, Sackova V, Solar P, Horvath V, Hofmanova J, Kozubik A, Fedorocko P 2007 Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells. Photochem Photobiol 83: 1174–1185
Grizzi F, Colombo P, Taverna G, Chiriva-Internati M, Cobos E, Graziotti P, Muzzio PC, Dioguardi N 2007 Geometry of human vascular system: is it an obstacle for quantifying antiangiogenic therapies?. Appl Immunohistochem Mol Morphol 15: 134–139
Badiavas EV, Ford D, Liu P, Kouttab N, Morgan J, Richards A, Maizel A 2007 Long-term bone marrow culture and its clinical potential in chronic wound healing. Wound Repair Regen 15: 856–865
Malda J, Klein TJ, Upton Z 2007 The roles of hypoxia in the in vitro engineering of tissues. Tissue Eng 13: 2153–2162
Nangaku M, Izuhara Y, Takizawa S, Yamashita T, Fujii-Kuriyama Y, Ohneda O, Yamamoto M, van Ypersele de Strihou C, Hirayama N, Miyata T 2007 A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia. Arterioscler Thromb Vasc Biol 27: 2548–2554
Callegari A, Bollini S, Iop L, Chiavegato A, Torregrossa G, Pozzobon M, Gerosa G, De CP, Elvassore N, Sartore S 2007 Neovascularization induced by porous collagen scaffold implanted on intact and cryoinjured rat hearts. Biomaterials 28: 5449–5461
Shujia J, Haider HK, Idris NM, Lu G, Ashraf M 2008 Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. Cardiovasc Res 77: 525–533. Doi:10.1093/cvr/cvm077
Falanga V, Iwamoto S, Chartier M, Yufit T, Butmarc J, Kouttab N, Shrayer D, Carson P 2007 Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng 13: 1299–1312
Li X, Zheng L, Peng F, Qi C, Zhang X, Zhou A, Liu Z, Wu S 2007 Recombinant thymosin beta 4 can promote full-thickness cutaneous wound healing. Protein Expr Purif 56: 229–236
Aird WC 2007 Phenotypic heterogeneity of the endothelium: II. Representative vascular beds. Circ Res 100: 174–190
Naik-Mathuria B, Gay AN, Zhu X, Yu L, Cass DL, Olutoye OO 2007 Age-dependent recruitment of neutrophils by fetal endothelial cells: implications in scarless wound healing. J Pediatr Surg 42: 166–171
Sheehan P 2006 Early change in wound area as a predictor of healing in diabetic foot ulcers: knowing “when to say when”. Plast Reconstr Surg 117: 245S–247S
Steed DL, Attinger C, Colaizzi T, Crossland M, Franz M, Harkless L, Johnson A, Moosa H, Robson M, Serena T, Sheehan P, Veves A, Wiersma-Bryant L 2006 Guidelines for the treatment of diabetic ulcers. Wound Repair Regen 14: 680–692
Fife CE, Buyukcakir C, Otto G, Sheffield P, Love T, Warriner R III 2007 Factors influencing the outcome of lower-extremity diabetic ulcers treated with hyperbaric oxygen therapy. Wound Repair Regen 15: 322–331
Spilker RL, Feinstein JA, Parker DW, Reddy VM, Taylor CA 2007 Morphometry-based impedance boundary conditions for patient-specific modeling of blood flow in pulmonary arteries. Ann Biomed Eng 35: 546–559
Souza BR, Cardoso JF, Amadeu TP, Desmouliere A, Costa AM 2005 Sympathetic denervation accelerates wound contraction but delays reepithelialization in rats. Wound Repair Regen 13: 498–505
Rossi EL 2003 Gene expression, neurogenesis, and healing: psychosocial genomics of therapeutic hypnosis. Am J Clin Hypn 45: 197–216
Meyer SC 2003 DNA and the origin of life: information, specification, and explanation. In: Campbell JA, Meyer SC (eds) Darwinism, Design, and Public Education. Michigan State University Press, East Lansing, pp 1–544
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We thank Dr. M. Goldirova of Safarik University and colleagues from the Saban Research Institute for consultations and a review of the text.
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This interdisciplinary work was supported by the following independent research funds across different authors' institutions: K99DE018459 (NIDCR, NIH), R01GM055081 (NIGMS, NIH), 1/4320/07 (VEGA, SK), LPP-0155-06 (APVV, SK).
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Dudas, M., Wysocki, A., Gelpi, B. et al. Memory Encoded Throughout Our Bodies: Molecular and Cellular Basis of Tissue Regeneration. Pediatr Res 63, 502–512 (2008). https://doi.org/10.1203/PDR.0b013e31816a7453
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DOI: https://doi.org/10.1203/PDR.0b013e31816a7453
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