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J. J. Gozzo - One of the best experts on this subject based on the ideXlab platform.
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Prolonged Adult Skin allograft survival as a result of cotransplantation with neonatal tissue. The requirement for antigen sharing between graft and cotransplant.
Transplantation, 1992Co-Authors: T. G. Markees, S. R. De Fazio, J. J. GozzoAbstract:The survival of an Adult Skin allograft can be prolonged by a cotransplant of neonatal, but not Adult, Skin on the same recipient. We demonstrated this phenomenon using a C3HeB/FeJ (H-2k; C3H) Adult graft and neonatal cotransplant donors. The median survival time (MST) for Adult graft survival on B6AF1 (H-2a/b) recipients was 59 days on recipients treated with antilymphocyte serum and donor bone marrow cells. With Adult or neonatal cotransplants, the MSTs for Adult graft survival were 55 and > 100 days, respectively. Our current experiments explore the specificity of this phenomenon by substituting neonatal cotransplants of several allogeneic and partially allogeneic strains. Cotransplants that do not share the antigens presented by the Adult graft to the recipient as foreign do not produce any prolongation of Adult graft survival. Thus, cotransplants of Adult or neonatal C57BL/6J (H-2b) or A/J (H-2a) strain Skins had no significant effect on Adult C3H graft survival. In contrast to these results, neonatal (but not Adult) cotransplants that share presented antigens produce a significant cotransplant effect. The presence, on a recipient, of a neonatal cotransplant of CBA/J (H-2k) resulted in significant prolongation of Adult Skin grafts (MST > 150 days; P < 0.05). As well, on a different recipient strain (CAF1; H-2a/d), neonatal C3H-H-2o2/SfSn (H-2o2) Skin cotransplants, sharing only background antigens and H-2Dk with the Adult graft donor, caused a significant prolongation of Adult graft survival relative to that seen on recipients bearing only a single Adult graft (MSTs = 53 and 31 days; P < 0.05). Our results suggest that this graft-prolonging effect of neonatal cotransplantation requires that the cotransplant shares antigens with the Adult graft that are presented as foreign to the recipient.
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Induction of allograft tolerance with neonatal Skin.
Transplantation, 1991Co-Authors: F. Jamshidi, T. G. Markees, S. R. De Fazio, J. J. GozzoAbstract:B6AF1 recipients treated with various combinations of ALS, CsA, and BMC were grafted with C3H Skin from Adult or neonatal donors. A survival advantage of neonatal Skin compared with Adult Skin was clearly demonstrated in groups treated with ALS and CsA (median survival time [MST] = 89 days, neonatal Skin; 50 days, Adult Skin), ALS and BMC, (MST = 92 days, neonatal; 64 days, Adult Skin), or with ALS only (MST = 55 days and 35 days, respectively). In these groups only neonatal grafts were observed to survive greater than 100 days. Also, once it was underway, rejection of the neonatal Skin proceeded more slowly than that of Adult Skin. ALS/BMC/CsA treatment of Adult Skin recipients improved graft survival modestly (MST = 77 days, 20% of grafts surviving greater than 100 days). But neonatal graft survival was prolonged remarkably by the ALS/BMC/CsA treatment, with 95% of grafts surviving greater than 100 days and 84% surviving greater than 240 days. After bearing neonatal grafts for greater than 150 days, these mice were challenged with C3H Adult Skin grafts. The second grafts were uniformly accepted for greater than 135 additional days, but third-party grafts were rejected promptly. This specific tolerance could not be abrogated by injection of normal B6AF1 spleen cells, and rejection of the grafts by adoptively transferred sensitized cells was delayed (MST = 35 days). That the tolerance developed in response to grafting neonatal Skin to ALS/BMC/CsA-treated recipients extends to Adult tissue suggests that understanding of the immunoregulatory signal provided by the neonatal tissue might lead to a tolerogenic protocol for use with Adult allografts.
Michael R. Harrison - One of the best experts on this subject based on the ideXlab platform.
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modulation of the human homeobox genes prx 2 and hoxb13 in scarless fetal wounds
Journal of Investigative Dermatology, 1998Co-Authors: Eric J Stelnicki, Michael R. Harrison, Darrell L. Cass, Jeff Arbeit, Catherine Saner, Corey LargmanAbstract:Scarless healing of cutaneous wounds occurs in humans during the first two trimesters of development, but by birth all wounds are repaired with scar formation. To search for transcriptional regulatory genes that might mediate fetal tissue regeneration, we surveyed homeobox gene expression in proliferating fetal fibroblasts and in wounded and unwounded Skin. Two novel human homeobox genes, PRX-2 and HOXB13, were identified that were differentially expressed during fetal versus Adult wound healing. Both genes were predominantly expressed in proliferating fetal fibroblasts and developing dermis, and PRX-2 was downregulated in Adult Skin. In a model of scarless fetal Skin regeneration, PRX-2 expression was strongly increased compared with unwounded Skin and the signal was localized to the wounded dermis, the site of scarless repair. Conversely, in Adult Skin weak epidermal PRX-2 expression was observed, mRNA levels were not increased by wounding, and no dermal expression was detected. HOXB13 expression was decreased in wounded fetal tissue relative to unwounded fetal controls or wounded Adult Skin. Thus both HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal Skin development and cutaneous regeneration.
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The human homeobox genes MSX‐1, MSX‐2, and MOX‐1 are differentially expressed in the dermis and epidermis in fetal and Adult Skin
Differentiation; research in biological diversity, 1997Co-Authors: Eric J Stelnicki, Michael R. Harrison, Dennis R. Holmes, N. Scott Adzick, László G. Kömüves, Whitney Clavin, Corey LargmanAbstract:In order to identify homeobox genes which may regulate Skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal Skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and Adult human Skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal Skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in Adult Skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and Adult Skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in Adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in Adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in Skin development.
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Adult Skin Wounds in the Fetal Environment Heal with Scar Formation
Annals of surgery, 1994Co-Authors: Michael T. Longaker, David J. Whitby, Mark K. Ferguson, Hermann P. Lorenz, Michael R. HarrisonAbstract:Objective This study investigated the influence of the fetal environment on the healing characteristics of Adult Skin. Summary Background Data The remarkable ability of the fetus to heal without scarring is poorly understood. The unique qualities of fetal wound healing may be caused by the fetal environment, the fetal tissues, or a combination of both. There are numerous differences between the prenatal and postnatal environments that may play a role in the unique fetal response to injury. Methods Full-thickness Adult sheep Skin was transplanted onto the backs of 60-day-gestation fetal lambs (term, 145 days of gestation). The Adult Skin grafts were thus perfused by fetal blood and bathed in amniotic fluid. Previous work has demonstrated that, before midgestation, fetal lambs do not reject allogeneic Skin grafts. Forty days later (100 days of gestation), incisional wounds were made on both the Adult Skin graft and the adjacent fetal Skin. The wounds were harvested 14 days postwounding and analyzed by both light microscopy and immunohistochemical testing using antibodies to collagen types I, III, and VI. Results The wounds in the Adult Skin grafts healed with scar formation. This observation contrasts strongly with the scarless healing of the incisional fetal Skin wounds. Conclusions This study suggests that scarless fetal Skin healing properties are intrinsic to fetal Skin and are not primarily the result of the fetal environment.
T. G. Markees - One of the best experts on this subject based on the ideXlab platform.
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Prolonged Adult Skin allograft survival as a result of cotransplantation with neonatal tissue. The requirement for antigen sharing between graft and cotransplant.
Transplantation, 1992Co-Authors: T. G. Markees, S. R. De Fazio, J. J. GozzoAbstract:The survival of an Adult Skin allograft can be prolonged by a cotransplant of neonatal, but not Adult, Skin on the same recipient. We demonstrated this phenomenon using a C3HeB/FeJ (H-2k; C3H) Adult graft and neonatal cotransplant donors. The median survival time (MST) for Adult graft survival on B6AF1 (H-2a/b) recipients was 59 days on recipients treated with antilymphocyte serum and donor bone marrow cells. With Adult or neonatal cotransplants, the MSTs for Adult graft survival were 55 and > 100 days, respectively. Our current experiments explore the specificity of this phenomenon by substituting neonatal cotransplants of several allogeneic and partially allogeneic strains. Cotransplants that do not share the antigens presented by the Adult graft to the recipient as foreign do not produce any prolongation of Adult graft survival. Thus, cotransplants of Adult or neonatal C57BL/6J (H-2b) or A/J (H-2a) strain Skins had no significant effect on Adult C3H graft survival. In contrast to these results, neonatal (but not Adult) cotransplants that share presented antigens produce a significant cotransplant effect. The presence, on a recipient, of a neonatal cotransplant of CBA/J (H-2k) resulted in significant prolongation of Adult Skin grafts (MST > 150 days; P < 0.05). As well, on a different recipient strain (CAF1; H-2a/d), neonatal C3H-H-2o2/SfSn (H-2o2) Skin cotransplants, sharing only background antigens and H-2Dk with the Adult graft donor, caused a significant prolongation of Adult graft survival relative to that seen on recipients bearing only a single Adult graft (MSTs = 53 and 31 days; P < 0.05). Our results suggest that this graft-prolonging effect of neonatal cotransplantation requires that the cotransplant shares antigens with the Adult graft that are presented as foreign to the recipient.
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Induction of allograft tolerance with neonatal Skin.
Transplantation, 1991Co-Authors: F. Jamshidi, T. G. Markees, S. R. De Fazio, J. J. GozzoAbstract:B6AF1 recipients treated with various combinations of ALS, CsA, and BMC were grafted with C3H Skin from Adult or neonatal donors. A survival advantage of neonatal Skin compared with Adult Skin was clearly demonstrated in groups treated with ALS and CsA (median survival time [MST] = 89 days, neonatal Skin; 50 days, Adult Skin), ALS and BMC, (MST = 92 days, neonatal; 64 days, Adult Skin), or with ALS only (MST = 55 days and 35 days, respectively). In these groups only neonatal grafts were observed to survive greater than 100 days. Also, once it was underway, rejection of the neonatal Skin proceeded more slowly than that of Adult Skin. ALS/BMC/CsA treatment of Adult Skin recipients improved graft survival modestly (MST = 77 days, 20% of grafts surviving greater than 100 days). But neonatal graft survival was prolonged remarkably by the ALS/BMC/CsA treatment, with 95% of grafts surviving greater than 100 days and 84% surviving greater than 240 days. After bearing neonatal grafts for greater than 150 days, these mice were challenged with C3H Adult Skin grafts. The second grafts were uniformly accepted for greater than 135 additional days, but third-party grafts were rejected promptly. This specific tolerance could not be abrogated by injection of normal B6AF1 spleen cells, and rejection of the grafts by adoptively transferred sensitized cells was delayed (MST = 35 days). That the tolerance developed in response to grafting neonatal Skin to ALS/BMC/CsA-treated recipients extends to Adult tissue suggests that understanding of the immunoregulatory signal provided by the neonatal tissue might lead to a tolerogenic protocol for use with Adult allografts.
Eric J Stelnicki - One of the best experts on this subject based on the ideXlab platform.
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hoxb13 knockout Adult Skin exhibits high levels of hyaluronan and enhanced wound healing
The FASEB Journal, 2003Co-Authors: Judith A Mack, Susan R Abramson, Jerusha C Coffin, Edward V Maytin, James K. Rothrock, Vincent C Hascall, Corey Largman, Eric J StelnickiAbstract:SPECIFIC AIMSExpression levels of the transcriptional regulator HoxB13 are significantly reduced in human fetal cutaneous wounds that heal without a scar compared with unwounded controls. In contrast, HoxB13 down-regulation is not noted in human Adult cutaneous wounds vs. unwounded controls. We postulated that reducing or eliminating HoxB13 from Adult Skin could improve healing. To test this hypothesis, we evaluated incisional and excisional cutaneous wound healing in Adult Hoxb13 knockout (KO) mice.PRINCIPAL FINDINGS1. Hoxb13 is expressed in murine SkinHoxb13 mRNA is present in the epidermal and dermal layers of the Skin and in RNA derived from primary keratinocyte and fibroblast cell cultures. Hoxb13 protein is detected in the nucleus and cytoplasm of the epidermis, epithelial cells of the hair follicle, and dermal fibroblasts and is up-regulated at the wound site. These observations indicate a functional role for Hoxb13 in the epidermal and dermal layers of the Skin.2. Hoxb13 KO Adult Skin exhibits a t...
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modulation of the human homeobox genes prx 2 and hoxb13 in scarless fetal wounds
Journal of Investigative Dermatology, 1998Co-Authors: Eric J Stelnicki, Michael R. Harrison, Darrell L. Cass, Jeff Arbeit, Catherine Saner, Corey LargmanAbstract:Scarless healing of cutaneous wounds occurs in humans during the first two trimesters of development, but by birth all wounds are repaired with scar formation. To search for transcriptional regulatory genes that might mediate fetal tissue regeneration, we surveyed homeobox gene expression in proliferating fetal fibroblasts and in wounded and unwounded Skin. Two novel human homeobox genes, PRX-2 and HOXB13, were identified that were differentially expressed during fetal versus Adult wound healing. Both genes were predominantly expressed in proliferating fetal fibroblasts and developing dermis, and PRX-2 was downregulated in Adult Skin. In a model of scarless fetal Skin regeneration, PRX-2 expression was strongly increased compared with unwounded Skin and the signal was localized to the wounded dermis, the site of scarless repair. Conversely, in Adult Skin weak epidermal PRX-2 expression was observed, mRNA levels were not increased by wounding, and no dermal expression was detected. HOXB13 expression was decreased in wounded fetal tissue relative to unwounded fetal controls or wounded Adult Skin. Thus both HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal Skin development and cutaneous regeneration.
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The human homeobox genes MSX‐1, MSX‐2, and MOX‐1 are differentially expressed in the dermis and epidermis in fetal and Adult Skin
Differentiation; research in biological diversity, 1997Co-Authors: Eric J Stelnicki, Michael R. Harrison, Dennis R. Holmes, N. Scott Adzick, László G. Kömüves, Whitney Clavin, Corey LargmanAbstract:In order to identify homeobox genes which may regulate Skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal Skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and Adult human Skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal Skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in Adult Skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and Adult Skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in Adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in Adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in Skin development.
Magda M. W. Ulrich - One of the best experts on this subject based on the ideXlab platform.
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Healthy human second-trimester fetal Skin is deficient in leukocytes and associated homing chemokines.
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2016Co-Authors: Mariëlle Walraven, Wendy Talhout, Robert H. J. Beelen, Marjolein Van Egmond, Magda M. W. UlrichAbstract:The lack of immune cells in mid-gestational fetal Skin is often mentioned as a key factor underlying scarless healing. However, the scarless healing ability is conserved until long after the immune system in the fetus is fully developed. Therefore, we studied human second-trimester fetal Skin and compared the numbers of immune cells and chemokine levels from fetal Skin with Adult Skin. By using immunohistochemistry, we show that healthy fetal Skin contains significant lower numbers of CD68(+) -macrophages, Tryptase(+) -mast cells, Langerin(+) -Langerhans cells, CD1a(+) -dendritic cells, and CD3(+) -T cells compared to Adult Skin. Staining with an early lineage leukocyte marker, i.e., CD45, verified that the number of CD45(+) -immune cells was indeed significantly lower in fetal Skin but that sufficient numbers of immune cells were present in the fetal lymph node. No differences in the vascular network were observed between fetal and Adult Skin. Moreover, significant lower levels of lymphocyte chemokines CCL17, CCL21, and CCL27 were observed in fetal Skin. However, levels of inflammatory interleukins such as IL-6, IL-8, and IL-10 were undetectable and levels of CCL2 were similar in healthy fetal and Adult Skin. In conclusion, this study shows that second-trimester fetal Skin contains low levels of immune cells and leukocyte chemokines compared to Adult Skin. This immune cell deficiency includes CD45(+) leukocytes, despite the abundant presence of these cells in the lymph node. The immune deficiency in healthy second-trimester fetal Skin may result in reduced inflammation during wound healing, and could underlie the scarless healing capacities of the fetal Skin.
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Transforming growth factor-β (TGF-β) signaling in healthy human fetal Skin: A descriptive study
Journal of dermatological science, 2015Co-Authors: Mariëlle Walraven, Robert H. J. Beelen, Magda M. W. UlrichAbstract:Abstract Background TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and Adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. Objective The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and Adult Skin. Methods Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy Skin. Results All components of the canonical TGF-β pathway were present in unwounded fetal Skin. Compared to Adult Skin, fetal Skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and Adult Skin. Conclusion This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and Adult Skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing.
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Comparison between human fetal and Adult Skin
Archives of Dermatological Research, 2010Co-Authors: Neeltje A. Coolen, Kelly C. W. M. Schouten, Esther Middelkoop, Magda M. W. UlrichAbstract:Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal Skin itself, knowledge of the fetal Skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and Adult Skin. In the human fetal Skin (ranging from 13 to 22 weeks’ gestation) and Adult Skin biopsies, the expression patterns of several epidermal proteins (K10, K14, K16, K17, SKALP, involucrin), basement membrane proteins, Ki-67, blood vessels and extracellular matrix proteins (fibronectin, chondroitin sulfate, elastin) were determined using immunohistochemistry. The expression profiles of K17, involucrin, dermal Ki-67, fibronectin and chondroitin sulfate were higher in the fetal Skin than in Adult Skin. In the fetal Skin, elastin was not present in the dermis, but it was found in the Adult Skin. The expression patterns of basement membrane proteins, blood vessels, K10, K14, K16 and epidermal Ki-67 were similar in human fetal Skin and Adult Skin. In this systematic overview, most of the differences between fetal and Adult Skin were found at the level of dermal extracellular matrix molecules expression. This study suggests that, especially, dermal components are important in fetal scarless healing.
