Surgical inflammatory stress: the embryo takes hold of the reins again (original) (raw)
Related papers
The wound-healing response and upregulated embryonic mechanisms: brothers-in-arms forever
Experimental Dermatology, 2012
The cutaneous wound-healing reaction occurs in overlapping but inter-related phases, which ultimately result in fibrosis. The pathophysiological mechanisms involved in fibrotic diseases, including organ-related and even systemic diseases, such as systemic sclerosis, could represent the successive systemic upregulation of extraembryonic-like phenotypes, that is, amniotic and vitelline phenotypes. These two extraembryonic-like phenotypes act on the injured tissue to induce a process similar to gastrulation, which occurs during the early phases of embryo development. The amniotic-like phenotype plays a leading role in the development of neurogenic responses with significant hydroelectrolytic alterations that essentially represent the development of open microcirculation within the injured tissue. In turn, through the overlapping expression of a vitelline-like phenotype, a bone marrow-related response is produced. Interstitial infiltration by molecular and cellular mediators ª
Journal of Pediatric Surgery, 1993
The minimal acute inflammatory response to tissue injury is one of the most dramatic differences between fetal and adult wound healing. Considering the prominent role of inflammation in adult tissue repair, this study tested the hypothesis that the minimal fetal inflammatory response to tissue injury plays a central role in the "scarless" fetal repair process. Sponge implants were treated with lethally irradiated or live bacteria and placed subcutaneously in fetal rabbits to test the ability of the fetus to mount an acute inflammatory response to bacterial antigens present at the wound site and to analyze the effects of this inflammatory response on fetal fibroplasia and neovascularization. After harvest, these implants were examined histologically for inflammation, fibroblast infiltration, collagen deposition, and neovascularization, and collagen deposition was measured using hydroxyproline quantitation by high-performance liquid chromatography. Bacteria-treated implants showed dose-dependent acute inflammatory responses and significant increases in collagen deposition compared with control sponges. Implants containing live bacteria demonstrated maximal fibroplasia and neovascularization. These findings suggest that, despite neutropenia and immaturity of the fetal immune system, the fetus is capable of mounting an acute inflammatory response to avirulent bacteria present at the wound site. Fetal inflammatory cells which respond to this bacterial stimulus appear capable of initiating an adult-like healing response. Thus, by failing to provide a bacterial stimulus for leukocyte recruitment at the site of tissue injury, the sterile fetal environment appears to play a role in effecting "scarless" fetal wound healing.
Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse
Developmental Dynamics, 1998
The recruitment of inflammatory cells to a wound may play an important role in the resulting cellular processes and ultimately the quality of the healing response in the fetus (scar-free healing) or the adult (scar-forming healing). Using a range of antibodies to monocytes and macrophages and also to different activation markers of activated macrophages, we have compared the inflammatory profile of scar-free healing E16 mouse fetal wounds to those of scarring adult wounds. In the fetal wound, small numbers of monocyte derived cells (MOMA-2 and F4/80 positive) are recruited to the wound by 3 hr post-wounding. No Mac-1 positive cells indicative of activated macrophages were observed until 18 hr post-wounding. Eventually all types of macrophages studied were recruited to both adult and fetal wound sites but the numbers and persistence of these cells are lower in the fetus than in the adult. B cells were detected in healing adult wounds but not in the fetal wounds. This absence of H-21-A positive (B) cells in murine fetal wounds could be associated with the low levels of activated Mac-1 positive macrophages at the murine fetal wound site. Activated macrophages in addition to releasing growth factors may also release signals to recruit B cells. Thus, the E16 mouse fetus can mount an inflammatory response to wounding. This response differs from that of the adult in the numbers of inflammatory cells recruited to the wound and the subpopulations of activated cells found at the wound site. This study indicates that there are complex differences between the inflammatory responses elicited in adult and fetal murine dermal wounds. These differences may determine the profile of growth factors and cytokines released at fetal and adult wound sites. Manipulation of either the numbers or the activation states of inflammatory cells at the adult wound site may be an approach to the control of scarring during adult wound healing.
Nutrition Reviews, 2007
Fetal development and growth occur in a sterile amniotic cavity while first exposure to microorganisms happens at birth. However, at least 25% of all preterm births, the leading cause of perinatal morbidity and mortality worldwide, occur in mothers with microbial invasion of the amniotic cavity. Microbial attack of the fetus takes place in approximately 10% of pregnancies with intra-amniotic infection, and the human fetus is capable of deploying an inflammatory response (cellular and humoral) in the mid-trimester of pregnancy. The onset of premature labor in the context of infection is mediated by pro-inflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor alpha (TNF-␣), as these cytokines are produced by intrauterine tissues in response to microbial products, can stimulate prostaglandin production, and induce labor in animals. Moreover, knockout experiments suggest that infection is less likely to lead to premature labor when the IL-1 and TNF signaling pathways are disrupted. A fetal inflammatory systemic response occurs in a fraction of fetuses exposed to microorganisms in utero, and is associated with the impending onset of labor as well as multisystem organ involvement. Neonates born with funisitis, the histologic marker of such inflammation, are at increased risk for neurologic handicap and cerebral palsy. Evidence has begun to accumulate that geneenvironment interactions determine the likelihood of preterm labor and delivery and, probably, the risk of fetal injury. Fetal inflammation has emerged as a major mechanism of disease responsible for complications in the perinatal period (in utero and in the first 28 days of life), as well as in infancy. Moreover, reprogramming of the fetal immune response may predispose to diseases in adulthood.
The biology and therapeutic implications of fetal wound healing
Clinical Materials, 1991
Wound healing in the fetus is very different from wound healing in the adult. Fetal skin wounds heal without scar formation and are characterized by rapid re-epithelialization, a wound matrix rich in hyaluronic acid, and a pattern of wound collagen deposition that resembles unwounded skin. The mechanisms that regulate this highly organized repair process are unknown, but understanding these mechanisms may allow postnatal wound healing to be made more fetal-like.
Scarless wound healing in the mammalian fetus
Surgery, gynecology & obstetrics, 1992
Fetal wound healing is a remarkable process that is fundamentally different than postnatal healing. Healing of primarily closed, linear wounds occurs rapidly and without scarring. In late gestational age fetal sheep, a transition to adult-like healing occurs as evidenced by minimal scar formation. Acute inflammation is not involved, fibroblast recruitment and proliferation is minimal, the matrix of the wounds is enriched with HA and collagen deposition is highly organized so that scarring is minimal or nonexistent. Open wounds in several species do not contract, an observation that may be because of an inhibitor of contraction in amniotic fluid. The underlying mechanisms that regulate fetal wound repair are currently not well understood. An altered supply or activity of growth factors may be instrumental. Fibroblasts may preferentially produce HA secondary to a factor present within the fetal system, and HA may influence cellular and matrix events within the wound. As greater knowle...
Naturally acquired regulatory mechanism of perioperative cytokine response in neonates
Pediatric Surgery International, 2007
The inflammatory reaction is known to be controlled in neonates. We clarified the characteristics of cytokine profile in neonatal patients and assess its clinical significance. Serum levels of interleukin (IL)-6 and IL-1 receptor antagonist (ra) were determined in 152 pediatric patients and 33 each of maternal and cord bloods. Supernatant IL-1ra levels of cultured monocytes and granulocytes stimulated with IL-1b or LPS, and IL-1ra mRNA expression of granulocytes were assayed in 15 each of cord and healthy adult bloods. Although surgical stress in neonates was heavier than that in infants, there was no difference in the occurrence of postoperative morbidity and mortality. In neonates, the perioperative serum level of IL-1ra was significantly raised, and the postoperative IL-6 response was well controlled. The serum concentration of IL-1ra in cord blood was not different from that in maternal blood, whereas, the serum concentration of IL-6 in cord blood was significantly reduced than that in maternal blood. In granulocytes, significantly more IL-1ra was produced from cord than from adult blood. An IL-1ra predominant immune status in neonates may be a naturally acquired adaptation system and play a crucial role in attenuating acute inflammatory reaction in a vulnerable host defense.
Amniotic Mesenchymal Stem Cells Enhance Normal Fetal Wound Healing
Stem Cells and Development, 2011
Fetal wound healing involves minimal inflammation and limited scarring. Its mechanisms, which remain to be fully elucidated, hold valuable clues for wound healing modulation and the development of regenerative strategies. We sought to determine whether fetal wound healing includes a hitherto unrecognized cellular component. Two sets of fetal lambs underwent consecutive experiments at midgestation. First, fetuses received an intra-amniotic infusion of labeled autologous amniotic mesenchymal stem cells (aMSCs), in parallel to different surgical manipulations. Subsequently, fetuses underwent creation of 2 symmetrical, size-matched skin wounds, both encased by a titanium chamber. One of the chambers was left open and the other covered with a semipermeable membrane that allowed for passage of water and all molecules, but not any cells. Survivors from both experiments had their wounds analyzed at different time points before term. Labeled aMSCs were documented in all concurrent surgical wounds. Covered wounds showed a significantly slower healing rate than open wounds. Paired comparisons indicated significantly lower elastin levels in covered wounds at the mid time points, with no significant differences in collagen levels. No significant changes in hyaluronic acid levels were detected between the wound types. Immunohistochemistry for substance P was positive in both open and covered wounds. We conclude that fetal wound healing encompasses an autologous yet exogenous cellular component in naturally occurring aMSCs. Although seemingly not absolutely essential to the healing process, amniotic cells expedite wound closure and enhance its extracellular matrix profile. Further scrutiny into translational implications of this finding is warranted.
Journal of Investigative Dermatology, 2007
Early human fetuses regenerate cutaneous wounds perfectly without scarring. However, transforming growth factor-b1 (TGF-b1), the cytokine linked with scarring in mature tissue, is also present during fetal wound repair, albeit transiently. We present a comparison of response to TGF-b1 by fibroblasts derived from early human fetal skin (non-scarring) and their mature (scarring) postnatal counterparts, which revealed that although fetal fibroblasts do indeed differentiate into myofibroblasts, this response is altogether more rapid and short-lived. Fetal fibroblasts also failed to exhibit the TGF-b1-induced increase in collagen (mRNA and protein) demonstrated by their postnatal counterparts. Fetal cells exhibited a comparatively short-lived or rapid phosphorylation of several components of the TGF-b1 signaling pathways: Smad2/3 and c-Jun N-terminal kinase. Unlike quiescent postnatal fibroblasts, quiescent fetal fibroblasts also phosphorylated extracellular signalregulated kinases in response to TGF-b1. These altered responses to TGF-b1 may well contribute to the transition between perfect regeneration and scar formation seen during development.