脂肪组织促进伤口愈合的研究进展
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摘要
目的总结脂肪组织促进伤口愈合的研究进展,并分析其临床应用前景。方法查阅近年来国内外有关脂肪组织促进伤口愈合的文献,并进行分析和总结。结果脂肪组织促进伤口愈合的研究取得了巨大进展,包括脂肪组织的细胞类型、细胞外基质、旁分泌信号等方面,均进行了深入研究。结论脂肪组织具有来源广泛、获取便捷等优点,在损伤修复和组织再生领域存在巨大潜力。下一步需探讨脂肪组织调控细胞功能及组织再生机制,以加快脂肪组织在伤口愈合领域的临床应用。
Objective To summarize recent progress in adipose tissue acting as a more efficient and ideal therapy to facilitate wound repair and evaluate the therapeutic values of adipose tissue. Methods The related literature about adipose tissue for wound healing in recent years was reviewed and analyzed. Results Enormous studies focus on the capacity of adipose tissue to accelerate wound healing including cellular components, extracellular matrix, and paracrine signaling have been investigated. Conclusion Adipose tissue has generated great interest in recent years because of unique advantages such as abundant and accessible source, thriven potential to enhance the regeneration and repair of damaged tissue. However, there is still a need to explore the mechanism that adipose tissue regulates cellular function and tissue regeneration in order to facilitate clinical application of adipose tissue in wound healing.
Objective To summarize recent progress in adipose tissue acting as a more efficient and ideal therapy to facilitate wound repair and evaluate the therapeutic values of adipose tissue. Methods The related literature about adipose tissue for wound healing in recent years was reviewed and analyzed. Results Enormous studies focus on the capacity of adipose tissue to accelerate wound healing including cellular components, extracellular matrix, and paracrine signaling have been investigated. Conclusion Adipose tissue has generated great interest in recent years because of unique advantages such as abundant and accessible source, thriven potential to enhance the regeneration and repair of damaged tissue. However, there is still a need to explore the mechanism that adipose tissue regulates cellular function and tissue regeneration in order to facilitate clinical application of adipose tissue in wound healing.
引文
1 Tricco AC, Cogo E, Isaranuwatchai W, et al. A systematic review of cost-effectiveness analyses of complex wound interventions reveals optimal treatments for specific wound types. BMC Med, 2015,13(1):90.
2 Powers JG, Higham C, Broussard K, et al. Wound healing and treating wounds:Chronic wound care and management. J Am Acad Dermatol, 2016, 74(4):607-625.
3 Klein J, Permana PA, Owecki M, et al. What are subcutaneous adipocytes really good for? Exp Dermatol, 2007,16(1):45-47.
4 Scherer PE. Adipose tissue:from lipid storage compartment to endocrine organ. Diabetes,2006, 55(6):1537-1545.
5 Romacho T, Elsen M, Rohrborn D, et al. Adipose tissue and its role in organ crosstalk. Acta Physiol(Oxf), 2014, 210(4):733-753.
6 Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 2011, 11(2):85-97.
7 Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell, 2008, 135(2):240.
8 Tang W, Zeve D, Suh JM, et al. White fat progenitor cells reside in the adipose vasculature. Science, 2008,322(5901):583-586.
9 Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, et al.Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure Cytotherapy, 2006, 8(2):166-177.
10 Kim WS, Park BS, Sung JH. The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin Biol Ther, 20099(7):879-887.
11熊佳超,宋建星.脂肪来源干细胞治疗难愈性创面的研究进展中国修复重建外科杂志,2018, 32(4):457-461.
12 Sun M, He Y, Zhou T, et al. Adipose extracellular matrix/stromal vascular fraction gel secretes angiogenic factors and enhancesskin wound healing in a murine model. Biomed Res Int, 2017, 2017(1):3105780.
13 Yao Y, Dong Z, Liao Y, et al. Adipose extracellular matrix/stromal vascular fraction gel:a novel adipose tissue-derived injectable for stem cell therapy. Plastic Reconstr Surg, 2017, 139(4):867-879.
14 Hoy AJ, Balaban S, Saunders DN. Adipocyte-tumor cell metabolic crosstalk in breast cancer. Trends Mol Med, 2017,23(5):381-392.
15 Maurizi G, Della GL, Maurizi A, et al. Adipocytes properties and crosstalk with immune system in obesity-related inflammation.J Cellular Physiology, 2018, 233(1):88-97.
16 Trayhurn P, Wood IS. Adipokines:inflammation and the pleiotropic role of white adipose tissue. Br J Nutr, 2004, 92(3):347-355.
17 Schmidt BA, Horsley V. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development, 2013,140(7):1517-1527.
18 Guerrero-Juarez CF,Plikus MV. Emerging nonmetabolic functions of skin fat. Nature Reviews Endocrinology, 2018,14:163-173.
19 Plikus MV, Guerrero-Juarez CF, Ito M, et al. Regeneration of fat cells from myofibroblasts during wound healing. Science, 2017,355(6326):748-752.
20 Rivera-Gonzalez G, Shook B, Horsley V. Adipocytes in skin health and disease. Cold Spring Harb Perspect Med, 2014,4(3):a015271.
21 Buchon N, Silverman N, Cherry S. Immunity in drosophila melanogaster——from microbial recognition to whole-organism physiology. Nat Rev Immunol, 2014,14(12):796-810.
22 Zhang LJ, Guerrero-Juarez CF, Hata T, et al. Innate immunity.Dermal adipocytes protect against invasive. Staphylococcus aureus skin infection. Science, 2015, 347(6217):67-71.
23 Franz A, Wood W, Martin P. Fat body cells are motile and actively migrate to wounds to drive repair and prevent infection. Dev Cell,2018,44(4):460-470.e3.
24 Mariman EC, Wang P. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell Mol Life Sci, 2010,67(8):1277-1292.
25 Pierleoni C, Verdenelli F, Castellucci M, et al. Fibronectins and basal lamina molecules expression in human subcutaneous white adipose tissue. Eur J Histochem, 1998, 42(3):183-188.
26 Louis F, Pannetier P, Souguir Z, et al. A biomimetic hydrogel functionalized with adipose ECM components as a microenvironment for the 3D culture of human and murine adipocytes.Biotechnology&Bioengineering, 2017, 114(8):1813-1824.
27 Flynn LE. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials, 2010, 31(17):4715-4724.
28 Dong J, Yu M, Zhang Y, et al. Recent developments and clinical potential on decellularized adipose tissue. J Biomed Mater Res A,2018,106(9):2563-2574.
29 Shahin TB, Vaishnav KV, Watchman M, et al. Tissue augmentation with allograft adipose matrix for the diabetic foot in remission. Plast Reconstr Surg Glob Open, 2017, 5(10):e1555.
30 Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol, 2005,115(5):911-919.
31 Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord,1998,22(12):1145-1158.
32 Masuzaki H, Ogawa Y, Isse N, et al. Human obese gene expression.Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes, 1995, 44(7):855-858.
33 Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372(6505):425-432.
34 Masuzaki H, Ogawa Y, Sagawa N, et al. Nonadipose tissue production of leptin:leptin as a novel placenta-derived hormone in humans. Nat Med, 1997, 3(9):1029-1033.
35 Bado A, Levasseur S, Attoub S, et al. The stomach is a source of leptin. Nature, 1998, 394(6695):790-793.
36 Wang J, Liu R, Hawkins M, et al. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature, 1998,393(6686):684-688.
37 Morash B, Li A, Murphy PR, et al. Leptin gene expression in the brain and pituitary gland. Endocrinology, 1999, 140(12):5995-5998.
38 Frank S, Stallmeyer B, Kampfer H, et al. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest, 2000, 106(4):501-509.
39 Ring BD, Scully S, Davis CR, et al. Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice. Endocrinology, 2000, 141(1):446-449.
40 Park HY, Kwon HM, Lim HJ, et al. Potential role of leptin in angiogenesis:leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med, 2001, 33(2):95-102.
41 Sierra-Honigmann MR, Nath AK, Murakami C, et al. Biological action of leptin as an angiogenic factor. Science, 1998, 281(5383):1683-1686.
42 Stallmeyer B, Kampfer H, Podda M, et al. A novel keratinocyte mitogen:regulation of leptin and its functional receptor in skin repair. J Invest Dermatol, 2001, 117(1):98-105.
43 Tadokoro S, Ide S, Tokuyama R, et al. Leptin promotes wound healing in the skin. PLoS One, 2015, 10(3):e0121242.
44李培兵,金宏,刘佃辛,等.瘦素促进皮肤创伤大鼠胶原合成的实研验究.中国应用生理学杂志,2011,27(1):72-74.
45 Goren I, Kampfer H, Podda M, et al. Leptin and wound inflammation in diabetic ob/ob mice:differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes, 2003,52(11):2821-2832.
46 Liapaki I, Anagnostoulis S, Karayiannakis A, et al. Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats. Acta Cir Bras, 2008, 23(2):118-124.
47文辉才,巫国辉,陈雯,等.局部应用瘦素对大鼠烫伤创面愈合的实验研究.南方医科大学学报,2012, 32(5):703-706.
48 El-Deeb AM, Fansa HA, Wahba OM. The expression of leptin in oral wound healing in diabetes mellitus:An experimental study. Int J Health Sci(Qassim), 2018, 12(2):22-25.
49 Umeki H, Tokuyama R, Ide S, et al. Leptin promotes wound healing in the oral mucosa. PLoS One, 2014, 9(7):e101984.
50 Tanigawa T, Watanabe T, Otani K, et al. Leptin promotes gastric ulcer healing via upregulation of vascular endothelial growth factor. Digestion, 2010, 81(2):86-95.
51 Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to Clq, produced exclusively in adipocytes. J Biol Chem,1995, 270(45):26746-26749.
52 Beltowski J. Adiponectin and resistin-new hormones of white adipose tissue. Med Sci Monit, 2003, 9(2):R55-R61.
53 Wang Y, Lam KS, Yau MH, et al. Post-translational modifications of adiponectin:mechanisms and functional implications. Biochem J, 2008,409(3):623-633.
54 Shibata S, Tada Y, Asano Y, et al. Adiponectin regulates cutaneous wound healing by promoting keratinocyte proliferation and migration via the ERK signaling pathway. J Immunol, 2012, 189(6):3231-3241.
55 Salathia NS, Shi J, Zhang J, et al. An in vivo screen of secreted proteins identifies adiponectin as a regulator of murine cutaneous wound healing. J Invest Dermatol, 2013, 133(3):812-821.
56 Ezure T,Amano S. Adiponectin and leptin up-regulate extracellular matrix production by dermal fibroblasts. Biofactors,2007, 31(3-4):229-236.
57 Ouchi N, Kobayashi H, Kihara S, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem,2004,279(2):1304-1309.
58 Nakamura N, Naruse K, Matsuki T, et al. Adiponectin promotes migration activities of endothelial progenitor cells via Cdc42/Racl.FEBS Letters, 2009, 583(15):2457-2463.
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2 Powers JG, Higham C, Broussard K, et al. Wound healing and treating wounds:Chronic wound care and management. J Am Acad Dermatol, 2016, 74(4):607-625.
3 Klein J, Permana PA, Owecki M, et al. What are subcutaneous adipocytes really good for? Exp Dermatol, 2007,16(1):45-47.
4 Scherer PE. Adipose tissue:from lipid storage compartment to endocrine organ. Diabetes,2006, 55(6):1537-1545.
5 Romacho T, Elsen M, Rohrborn D, et al. Adipose tissue and its role in organ crosstalk. Acta Physiol(Oxf), 2014, 210(4):733-753.
6 Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 2011, 11(2):85-97.
7 Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell, 2008, 135(2):240.
8 Tang W, Zeve D, Suh JM, et al. White fat progenitor cells reside in the adipose vasculature. Science, 2008,322(5901):583-586.
9 Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, et al.Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure Cytotherapy, 2006, 8(2):166-177.
10 Kim WS, Park BS, Sung JH. The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin Biol Ther, 20099(7):879-887.
11熊佳超,宋建星.脂肪来源干细胞治疗难愈性创面的研究进展中国修复重建外科杂志,2018, 32(4):457-461.
12 Sun M, He Y, Zhou T, et al. Adipose extracellular matrix/stromal vascular fraction gel secretes angiogenic factors and enhancesskin wound healing in a murine model. Biomed Res Int, 2017, 2017(1):3105780.
13 Yao Y, Dong Z, Liao Y, et al. Adipose extracellular matrix/stromal vascular fraction gel:a novel adipose tissue-derived injectable for stem cell therapy. Plastic Reconstr Surg, 2017, 139(4):867-879.
14 Hoy AJ, Balaban S, Saunders DN. Adipocyte-tumor cell metabolic crosstalk in breast cancer. Trends Mol Med, 2017,23(5):381-392.
15 Maurizi G, Della GL, Maurizi A, et al. Adipocytes properties and crosstalk with immune system in obesity-related inflammation.J Cellular Physiology, 2018, 233(1):88-97.
16 Trayhurn P, Wood IS. Adipokines:inflammation and the pleiotropic role of white adipose tissue. Br J Nutr, 2004, 92(3):347-355.
17 Schmidt BA, Horsley V. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development, 2013,140(7):1517-1527.
18 Guerrero-Juarez CF,Plikus MV. Emerging nonmetabolic functions of skin fat. Nature Reviews Endocrinology, 2018,14:163-173.
19 Plikus MV, Guerrero-Juarez CF, Ito M, et al. Regeneration of fat cells from myofibroblasts during wound healing. Science, 2017,355(6326):748-752.
20 Rivera-Gonzalez G, Shook B, Horsley V. Adipocytes in skin health and disease. Cold Spring Harb Perspect Med, 2014,4(3):a015271.
21 Buchon N, Silverman N, Cherry S. Immunity in drosophila melanogaster——from microbial recognition to whole-organism physiology. Nat Rev Immunol, 2014,14(12):796-810.
22 Zhang LJ, Guerrero-Juarez CF, Hata T, et al. Innate immunity.Dermal adipocytes protect against invasive. Staphylococcus aureus skin infection. Science, 2015, 347(6217):67-71.
23 Franz A, Wood W, Martin P. Fat body cells are motile and actively migrate to wounds to drive repair and prevent infection. Dev Cell,2018,44(4):460-470.e3.
24 Mariman EC, Wang P. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell Mol Life Sci, 2010,67(8):1277-1292.
25 Pierleoni C, Verdenelli F, Castellucci M, et al. Fibronectins and basal lamina molecules expression in human subcutaneous white adipose tissue. Eur J Histochem, 1998, 42(3):183-188.
26 Louis F, Pannetier P, Souguir Z, et al. A biomimetic hydrogel functionalized with adipose ECM components as a microenvironment for the 3D culture of human and murine adipocytes.Biotechnology&Bioengineering, 2017, 114(8):1813-1824.
27 Flynn LE. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials, 2010, 31(17):4715-4724.
28 Dong J, Yu M, Zhang Y, et al. Recent developments and clinical potential on decellularized adipose tissue. J Biomed Mater Res A,2018,106(9):2563-2574.
29 Shahin TB, Vaishnav KV, Watchman M, et al. Tissue augmentation with allograft adipose matrix for the diabetic foot in remission. Plast Reconstr Surg Glob Open, 2017, 5(10):e1555.
30 Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol, 2005,115(5):911-919.
31 Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord,1998,22(12):1145-1158.
32 Masuzaki H, Ogawa Y, Isse N, et al. Human obese gene expression.Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes, 1995, 44(7):855-858.
33 Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372(6505):425-432.
34 Masuzaki H, Ogawa Y, Sagawa N, et al. Nonadipose tissue production of leptin:leptin as a novel placenta-derived hormone in humans. Nat Med, 1997, 3(9):1029-1033.
35 Bado A, Levasseur S, Attoub S, et al. The stomach is a source of leptin. Nature, 1998, 394(6695):790-793.
36 Wang J, Liu R, Hawkins M, et al. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature, 1998,393(6686):684-688.
37 Morash B, Li A, Murphy PR, et al. Leptin gene expression in the brain and pituitary gland. Endocrinology, 1999, 140(12):5995-5998.
38 Frank S, Stallmeyer B, Kampfer H, et al. Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest, 2000, 106(4):501-509.
39 Ring BD, Scully S, Davis CR, et al. Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice. Endocrinology, 2000, 141(1):446-449.
40 Park HY, Kwon HM, Lim HJ, et al. Potential role of leptin in angiogenesis:leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med, 2001, 33(2):95-102.
41 Sierra-Honigmann MR, Nath AK, Murakami C, et al. Biological action of leptin as an angiogenic factor. Science, 1998, 281(5383):1683-1686.
42 Stallmeyer B, Kampfer H, Podda M, et al. A novel keratinocyte mitogen:regulation of leptin and its functional receptor in skin repair. J Invest Dermatol, 2001, 117(1):98-105.
43 Tadokoro S, Ide S, Tokuyama R, et al. Leptin promotes wound healing in the skin. PLoS One, 2015, 10(3):e0121242.
44李培兵,金宏,刘佃辛,等.瘦素促进皮肤创伤大鼠胶原合成的实研验究.中国应用生理学杂志,2011,27(1):72-74.
45 Goren I, Kampfer H, Podda M, et al. Leptin and wound inflammation in diabetic ob/ob mice:differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes, 2003,52(11):2821-2832.
46 Liapaki I, Anagnostoulis S, Karayiannakis A, et al. Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats. Acta Cir Bras, 2008, 23(2):118-124.
47文辉才,巫国辉,陈雯,等.局部应用瘦素对大鼠烫伤创面愈合的实验研究.南方医科大学学报,2012, 32(5):703-706.
48 El-Deeb AM, Fansa HA, Wahba OM. The expression of leptin in oral wound healing in diabetes mellitus:An experimental study. Int J Health Sci(Qassim), 2018, 12(2):22-25.
49 Umeki H, Tokuyama R, Ide S, et al. Leptin promotes wound healing in the oral mucosa. PLoS One, 2014, 9(7):e101984.
50 Tanigawa T, Watanabe T, Otani K, et al. Leptin promotes gastric ulcer healing via upregulation of vascular endothelial growth factor. Digestion, 2010, 81(2):86-95.
51 Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to Clq, produced exclusively in adipocytes. J Biol Chem,1995, 270(45):26746-26749.
52 Beltowski J. Adiponectin and resistin-new hormones of white adipose tissue. Med Sci Monit, 2003, 9(2):R55-R61.
53 Wang Y, Lam KS, Yau MH, et al. Post-translational modifications of adiponectin:mechanisms and functional implications. Biochem J, 2008,409(3):623-633.
54 Shibata S, Tada Y, Asano Y, et al. Adiponectin regulates cutaneous wound healing by promoting keratinocyte proliferation and migration via the ERK signaling pathway. J Immunol, 2012, 189(6):3231-3241.
55 Salathia NS, Shi J, Zhang J, et al. An in vivo screen of secreted proteins identifies adiponectin as a regulator of murine cutaneous wound healing. J Invest Dermatol, 2013, 133(3):812-821.
56 Ezure T,Amano S. Adiponectin and leptin up-regulate extracellular matrix production by dermal fibroblasts. Biofactors,2007, 31(3-4):229-236.
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