间充质干细胞在烧伤创面修复中的研究进展
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摘要
烧伤为软组织损伤最常见的形式,严重时会导致广泛深度的伤口甚至死亡。特殊部位、广泛面积、深度较深的烧伤常因愈合过程中的疼痛,美观以及对生活造成不便等问题引起患者严重的精神压力。目前烧伤的治疗仍是比较困难的,特别是严重的烧伤。治疗烧伤愈合的常规选择包括自体、异体和异种移植,但这3种方法也有缺点。自体移植虽是烧伤治疗的金标准,但是临床应用不是很广泛。而异体移植和异种移植会产生疾病传播的风险和较低的融入愈合组织的能力。间充质干细胞由于其低免疫原性、多向分化潜能、来源广泛等优点,在临床上得到广泛使用和研究。
Burns are the most common form of soft tissue injury,which can lead to extensive depth of wounds and even death in severe cases. Burns with special parts,extensive areas,and deep depths often cause severe mental stress in patients due to pain during healing,aesthetic reason,and inconvenience to life. Currently,the treatment of burns is still difficult,especially severe burns. Conventional options for burn healing include autologous,allogeneic,and xenogeneic transplant,but these three methods also have disadvantages. Autologous transplantation is the gold standard for burn treatment,though it is not widely used in clinical. Allogeneic and xenogeneic transplantation have a risk of disease spread and a low ability to integrate into healing tissue. Mesenchymal stem cells are widely used and studied in clinical practice due to their low immunogenicity,multi-directional differentiation potential,and wide range of sources.
Burns are the most common form of soft tissue injury,which can lead to extensive depth of wounds and even death in severe cases. Burns with special parts,extensive areas,and deep depths often cause severe mental stress in patients due to pain during healing,aesthetic reason,and inconvenience to life. Currently,the treatment of burns is still difficult,especially severe burns. Conventional options for burn healing include autologous,allogeneic,and xenogeneic transplant,but these three methods also have disadvantages. Autologous transplantation is the gold standard for burn treatment,though it is not widely used in clinical. Allogeneic and xenogeneic transplantation have a risk of disease spread and a low ability to integrate into healing tissue. Mesenchymal stem cells are widely used and studied in clinical practice due to their low immunogenicity,multi-directional differentiation potential,and wide range of sources.
引文
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[6]Tiwari VK.Burn wound:How it differs from other wounds?[J].Indian J Plast Surg,2012,45(2):364-373.
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[14]许若山,王永光,杨旭峰,等.人工真皮支架修复猪Ⅲ度烧伤动物模型的构建[J].健康研究,2010,30(3):171-174.
[15]Zhanzeng F,Yurong Z,Chuangang Y,et al.Basic investigation into the present burn care system in China:Burn units,doctors,nurses,beds and special treatment equipment[J].Burns,2015,41(2):279-288.
[16]Shen YI,Song HG,Papa A,et al.Acellular hydrogels for regenerative burn wound healing:Translation from a porcine model[J].J Invest Dermatol,2015,135(10):2519-2529.
[17]陈立力,赖章丽,邢颜超.人脐带沃顿胶间充质干细胞研究及其在心血管组织工程中的应用现状[J].中国美容医学,2013,22(3):401-404.
[18]Liu L,Yu Y,Hou Y,et al.Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats[J].PLo S One,2014,9(2):e88348.
[19]Lawton G,Dheansa B.The management of major burns-a surgical perspective[J].Curr Anaesth Crit Care,2008,19(5):275-281.
[20]Lorenti A.Wound Healing:From epidermis culture to tissue engineering[J].Cell Biol,2012,1(2):17-29.
[21]Maxson S,Lopez EA,Yoo D,et al.Concise review:Role of mesenchymal stem cells in wound repair[J].Stem Cells Transl Med,2012,1(2):142-149.
[22]Xi J,Yan X,Zhou J,et al.Mesenchymal stem cells in tissue repairing and regeneration:Progress and future[J].Burns Trauma,2013,1(1):13-20.
[23]Girdlestone J.Mesenchymal stromal cells with enhanced therapeutic properties[J].Immunotherapy,2016,8(12):1405-1416.
[24]Qiao C,Xu W,Zhu W,et al.Human mesenchymal stem cells isolated from the umbilical cord[J].Cell Biol Int,2008,32(1):8-15.
[25]Boxall SA,Jones E.Markers for characterization of bone marrow multipotential stromal cells[J].Stem Cells Int,2012,2012:975871.
[26]Caliari-Oliveira C,Yaochite JN,Ramalho LN,et al.Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model[J].Cell Transplant,2016,25(2):201-215.
[27]Shabbir A,Cox A,Rodriguez-Menocal L,et al.Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts,and enhance angiogenesis in vitro[J].Stem Cells Dev,2015,24(14):1635-1647.
[28]Kniazeva E,Kachgal S,Putnam AJ.Effects of extracellular matrix density and mesenchymal stem cells on neovascularization in vivo[J].Tissue Eng Part A,2011,17(7/8):905-914.
[29]Aga M,Bentz GL,Raffa S,et al.Exosomal HIF1alpha supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes[J].Oncogene,2014,33(37):4613-4622.
[30]Liu L,Li X,Yang J,et al.Comparison of systemic inflammation response and vital organ damage induced by severe burns in different area[J].Int J Clin Exp Pathol,2015,8(6):6367-6376.
[31]Kott M,Elke G,Reinicke M,et al.Acid sphingomyelinase serum activity predicts mortality in intensive care unit patients after systemic inflammation:A prospective cohort study[J].PLo S One,2014,9(11):e112323.
[32]Jackson WM,Nesti LJ,Tuan RS.Mesenchymal stem cell therapy for attenuation of scar formation during wound healing[J].Stem Cell Res Ther,2012,3(3):20.
[33]Huang L,Burd A.An update review of stem cell applications in burns and wound care[J].Indian J Plast Surg,2012,45(2):229-236.
[34]赵贵芳.脐带间充质干细胞及其来源外泌体修复皮肤损伤的机制研究[D].长春:吉林大学,2016.
[35]胡克苏,祁俊,蔡玉辉,等.人脐带间充质干细胞移植修复烧伤皮肤的机制[J].江苏医药,2014,40(7):759-761.
[36]Shi Y,Su J,Roberts AI,et al.How mesenchymal stem cells interact with tissue immune responses[J].Trends Immunol,2012,33(3):136-143.
[37]Arutyunyan I,Elchaninov A,Makarov A,et al.Umbilical cord as prospective source for mesenchymal stem cell-based therapy[J].Stem Cells Int,2016,2016:6901286.
[38]Middelkoop E,van den Bogaerdt AJ,Lamme EN,et al.Porcine wound models for skin substitution and burn treatment[J].Biomaterials,2004,25(9):1559-1567.
[39]张进进,范力星,余元伦,等.间充质干细胞移植对烧伤大鼠的炎症调节作用初探[J].国际生物医学工程杂志,2015,38(1):19-24,插5.
[40]Clover AJ,Kumar AH,Isakson M,et al.Allogeneic mesenchymal stem cells,but not culture modified monocytes,improve burn wound healing[J].Burns,2015,41(3):548-557.
[41]Natesan S,Wrice NL,Baer DG,et al.Debrided skin as a source of autologous stem cells for wound repair[J].Stem Cells,2011,29(8):1219-1230.
[42]Yamanishi H,Fujiwara S,Soma T.Perivascular localization of dermal stem cells in human scalp[J].Exp Dermatol,2012,21(1):78-80.
[43]Bouacida A,Rosset P,Trichet V,et al.Pericyte-like progenitors show high immaturity and engraftment potential as compared with mesenchymal stem cells[J].PLo S One,2012,7(11):e48648.
[44]Ema H,Suda T.Two anatomically distinct niches regulate stem cell activity[J].Blood,2012,120(11):2174-2181.
[45]Yoshikawa T Mitsuno H,Nonaka I,et al.Wound therapy by marrow mesenchymal cell transplantation[J].Plast Reconstr Surg,2008,121(3):860-877.
[46]Rasulov MF,Vasilchenkov AV,Onishchenko NA,et al.First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns[J].Bull Exp Biol Med,2005,139(1):141-144.
[47]Mansilla E,Marin GH,Berges M,et al.Cadaveric bone marrow mesenchymal stem cells:First experience treating a patient with large severe burns[J].Burns Trauma,2015,3:17.
[48]Wong M,Chua A,Tan BK.Cultured epithelial autografts for the coverage of large wounds:Minimizing skin graft donor sites in the sick patient[J].Eur J Plastic Surg,2013,36(6):371-376.
[49]Kua EH,Goh CQ,Ting Y,et al.Comparing the use of glycerol preserved and cryopreserved allogenic skin for the treatment of severe burns:Differences in clinical outcomes and in vitro tissue viability[J].Cell Tissue Bank,2012,13(2):269-279.
[50]Rattigan Y,Hsu JM,Mishra PJ,et al.Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu[J].Exp Cell Res,2010,316(20):3417-3424.
[51]Chester DL,Balderson DS,Papini RP.A review of keratinocyte delivery to the wound bed[J].J Burn Care Rehabil,2004,25(3):266-275.
[52]Burd A,Ahmed K,Lam S,et al.Stem cell strategies in burns care[J].Burns,2007,33(3):282-291.
[53]Shumakov VI,Onishchenko NA,Rasulov MF,et al.Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts[J].Bull Exp Biol Med,2003,136(2):192-195.
[2]Yang YJ,Li XL,Xue Y,et al.Bone marrow cells differentiation into organ cells using stem cell therapy[J].Eur Rev Med Pharmacol Sci,2016,20(13):2899-2907.
[3]Da SML,Chagastelles PC,Nardi NB.Mesenchymal stem cells reside in virtually all post-natal organs and tissues[J].J Cell Sci,2006,119(Pt 11):2204-2213.
[4]Seo BM,Miura M,Gronthos S,et al.Investigation of multipotent postnatal stem cells from human periodontal ligament[J].Lancet,2004,364(9429):149-155.
[5]Reinke JM,Sorg H.Wound repair and regeneration[J].Eur Surg Res,2012,49(1):35-43.
[6]Tiwari VK.Burn wound:How it differs from other wounds?[J].Indian J Plast Surg,2012,45(2):364-373.
[7]Brusselaers N,Monstrey S,Vogelaers D,et al.Severe burn injury in Europe:A systematic review of the incidence,etiology,morbidity,and mortality[J].Crit Care,2010,14(5):R188.
[8]Bhardwaj N,Chouhan D,Mandal BB.Tissue engineered skin and wound healing:Current strategies and future directions[J].Curr Pharm Des,2017,23(24):3455-3482.
[9]Wexler SA,Donaldson C,Denning-Kendall P,et al.Adult bone marrow is a rich source of human mesenchymal stem cells but umbilical cord and mobilized adult blood are not[J].Br JHaematol,2003,121(2):368-374.
[10]Shi C,Cheng T,Su Y,et al.Transplantation of dermal multipotent cells promotes survival and wound healing in rats with combined radiation and wound injury[J].Radiat Res,2004,162(1):56-63.
[11]Sasaki M,Abe R,Fujita Y,et al.Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type[J].J Immunol,2008,180(4):2581-2587.
[12]Peck MD.Epidemiology of burns throughout the world.PartⅠ:distributionand risk factors[J],Burns,2011,37(7):1087-1100.
[13]Lotter O,Held M,Schiefer J,et al.Utilization of laser Doppler flowmetry and tissue spectrophotometry for burn depth assessment using a miniature swine model[J].Wound Repair Regen,2015,23(1):132-136.
[14]许若山,王永光,杨旭峰,等.人工真皮支架修复猪Ⅲ度烧伤动物模型的构建[J].健康研究,2010,30(3):171-174.
[15]Zhanzeng F,Yurong Z,Chuangang Y,et al.Basic investigation into the present burn care system in China:Burn units,doctors,nurses,beds and special treatment equipment[J].Burns,2015,41(2):279-288.
[16]Shen YI,Song HG,Papa A,et al.Acellular hydrogels for regenerative burn wound healing:Translation from a porcine model[J].J Invest Dermatol,2015,135(10):2519-2529.
[17]陈立力,赖章丽,邢颜超.人脐带沃顿胶间充质干细胞研究及其在心血管组织工程中的应用现状[J].中国美容医学,2013,22(3):401-404.
[18]Liu L,Yu Y,Hou Y,et al.Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats[J].PLo S One,2014,9(2):e88348.
[19]Lawton G,Dheansa B.The management of major burns-a surgical perspective[J].Curr Anaesth Crit Care,2008,19(5):275-281.
[20]Lorenti A.Wound Healing:From epidermis culture to tissue engineering[J].Cell Biol,2012,1(2):17-29.
[21]Maxson S,Lopez EA,Yoo D,et al.Concise review:Role of mesenchymal stem cells in wound repair[J].Stem Cells Transl Med,2012,1(2):142-149.
[22]Xi J,Yan X,Zhou J,et al.Mesenchymal stem cells in tissue repairing and regeneration:Progress and future[J].Burns Trauma,2013,1(1):13-20.
[23]Girdlestone J.Mesenchymal stromal cells with enhanced therapeutic properties[J].Immunotherapy,2016,8(12):1405-1416.
[24]Qiao C,Xu W,Zhu W,et al.Human mesenchymal stem cells isolated from the umbilical cord[J].Cell Biol Int,2008,32(1):8-15.
[25]Boxall SA,Jones E.Markers for characterization of bone marrow multipotential stromal cells[J].Stem Cells Int,2012,2012:975871.
[26]Caliari-Oliveira C,Yaochite JN,Ramalho LN,et al.Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model[J].Cell Transplant,2016,25(2):201-215.
[27]Shabbir A,Cox A,Rodriguez-Menocal L,et al.Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts,and enhance angiogenesis in vitro[J].Stem Cells Dev,2015,24(14):1635-1647.
[28]Kniazeva E,Kachgal S,Putnam AJ.Effects of extracellular matrix density and mesenchymal stem cells on neovascularization in vivo[J].Tissue Eng Part A,2011,17(7/8):905-914.
[29]Aga M,Bentz GL,Raffa S,et al.Exosomal HIF1alpha supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes[J].Oncogene,2014,33(37):4613-4622.
[30]Liu L,Li X,Yang J,et al.Comparison of systemic inflammation response and vital organ damage induced by severe burns in different area[J].Int J Clin Exp Pathol,2015,8(6):6367-6376.
[31]Kott M,Elke G,Reinicke M,et al.Acid sphingomyelinase serum activity predicts mortality in intensive care unit patients after systemic inflammation:A prospective cohort study[J].PLo S One,2014,9(11):e112323.
[32]Jackson WM,Nesti LJ,Tuan RS.Mesenchymal stem cell therapy for attenuation of scar formation during wound healing[J].Stem Cell Res Ther,2012,3(3):20.
[33]Huang L,Burd A.An update review of stem cell applications in burns and wound care[J].Indian J Plast Surg,2012,45(2):229-236.
[34]赵贵芳.脐带间充质干细胞及其来源外泌体修复皮肤损伤的机制研究[D].长春:吉林大学,2016.
[35]胡克苏,祁俊,蔡玉辉,等.人脐带间充质干细胞移植修复烧伤皮肤的机制[J].江苏医药,2014,40(7):759-761.
[36]Shi Y,Su J,Roberts AI,et al.How mesenchymal stem cells interact with tissue immune responses[J].Trends Immunol,2012,33(3):136-143.
[37]Arutyunyan I,Elchaninov A,Makarov A,et al.Umbilical cord as prospective source for mesenchymal stem cell-based therapy[J].Stem Cells Int,2016,2016:6901286.
[38]Middelkoop E,van den Bogaerdt AJ,Lamme EN,et al.Porcine wound models for skin substitution and burn treatment[J].Biomaterials,2004,25(9):1559-1567.
[39]张进进,范力星,余元伦,等.间充质干细胞移植对烧伤大鼠的炎症调节作用初探[J].国际生物医学工程杂志,2015,38(1):19-24,插5.
[40]Clover AJ,Kumar AH,Isakson M,et al.Allogeneic mesenchymal stem cells,but not culture modified monocytes,improve burn wound healing[J].Burns,2015,41(3):548-557.
[41]Natesan S,Wrice NL,Baer DG,et al.Debrided skin as a source of autologous stem cells for wound repair[J].Stem Cells,2011,29(8):1219-1230.
[42]Yamanishi H,Fujiwara S,Soma T.Perivascular localization of dermal stem cells in human scalp[J].Exp Dermatol,2012,21(1):78-80.
[43]Bouacida A,Rosset P,Trichet V,et al.Pericyte-like progenitors show high immaturity and engraftment potential as compared with mesenchymal stem cells[J].PLo S One,2012,7(11):e48648.
[44]Ema H,Suda T.Two anatomically distinct niches regulate stem cell activity[J].Blood,2012,120(11):2174-2181.
[45]Yoshikawa T Mitsuno H,Nonaka I,et al.Wound therapy by marrow mesenchymal cell transplantation[J].Plast Reconstr Surg,2008,121(3):860-877.
[46]Rasulov MF,Vasilchenkov AV,Onishchenko NA,et al.First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns[J].Bull Exp Biol Med,2005,139(1):141-144.
[47]Mansilla E,Marin GH,Berges M,et al.Cadaveric bone marrow mesenchymal stem cells:First experience treating a patient with large severe burns[J].Burns Trauma,2015,3:17.
[48]Wong M,Chua A,Tan BK.Cultured epithelial autografts for the coverage of large wounds:Minimizing skin graft donor sites in the sick patient[J].Eur J Plastic Surg,2013,36(6):371-376.
[49]Kua EH,Goh CQ,Ting Y,et al.Comparing the use of glycerol preserved and cryopreserved allogenic skin for the treatment of severe burns:Differences in clinical outcomes and in vitro tissue viability[J].Cell Tissue Bank,2012,13(2):269-279.
[50]Rattigan Y,Hsu JM,Mishra PJ,et al.Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu[J].Exp Cell Res,2010,316(20):3417-3424.
[51]Chester DL,Balderson DS,Papini RP.A review of keratinocyte delivery to the wound bed[J].J Burn Care Rehabil,2004,25(3):266-275.
[52]Burd A,Ahmed K,Lam S,et al.Stem cell strategies in burns care[J].Burns,2007,33(3):282-291.
[53]Shumakov VI,Onishchenko NA,Rasulov MF,et al.Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts[J].Bull Exp Biol Med,2003,136(2):192-195.