[1]毛水红,张家鹏,张勇超,等.脐带间充质干细胞对重度糖尿病足溃疡创面愈合的促进作用[J].新乡医学院学报,2021,38(7):639-644.[doi:10.7683/xxyxyxb.2021.07.008]
　MAO Shuihong,ZHANG Jiapeng,ZHANG Yongchao,et al.Promoting effect of umbilical cord mesenchymal stem cells on wound healing of severe diabetic foot ulcer[J].Journal of Xinxiang Medical University,2021,38(7):639-644.[doi:10.7683/xxyxyxb.2021.07.008]
点击复制

脐带间充质干细胞对重度糖尿病足溃疡创面愈合的促进作用
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
38
期数:
2021年7
页码:
639-644
栏目:
临床研究
出版日期:
2021-07-05

文章信息/Info

Title:
Promoting effect of umbilical cord mesenchymal stem cells on wound healing of severe diabetic foot ulcer
作者:
毛水红1; 2; 张家鹏2; 张勇超2; 徐功志2; 吕　璐2; 任新华3; 孙钰椋1; 赵东轮2; 刘彦礼1; 郭志坤1
（1.河南省医用组织再生重点实验室，新乡医学院，河南　新乡　453003；2.新乡市第二人民医院伤口治疗科，河南　新乡　453002；3.河南省茵特赛尔生物技术有限公司，河南　新乡　453000）
Author(s):
MAO Shuihong1; 2; ZHANG Jiapeng2; ZHANG Yongchao2; XU Gongzhi2; LYU Lu2; REN Xinhua3; SUN Yuliang1; ZHAO Donglun2; LIU Yanli1; GUO Zhikun1
（1.Henan Key Laboratory of Medical Tissue Regeneration,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Department of Wound Treatment,the Second People′s Hospital of Xinxiang,Xinxiang 453002,Henan Province,China;3.Henan Intercell Biotechnology co.LTD,Xinxiang 453000,Henan Province,China）
关键词:
脐带间充质干细胞; 糖尿病足溃疡; 干细胞治疗; 创面愈合
Keywords:
umbilical cord mesenchymal stem cells; diabetic foot ulcer; stem cell based therapy; wound healing
分类号:
R259
DOI:
10.7683/xxyxyxb.2021.07.008
文献标志码:
A
摘要:
目的　探讨脐带间充质干细胞（UCMSCs）对重度糖尿病足溃疡（DFU）患者创面愈合的改善作用及其对肝肾功能的影响。方法　选择2019年6月于新乡市第二人民医院伤口治疗科接受常规治疗的1例女性DFU患者为研究对象，入院时患者创面宽度约为2 cm，长度8 cm，第1跖骨处向内连接，中间约有0.5 cm距离，正常组织暴露约有1/5，第3～5跖骨处全部被坏死组织覆盖，创面周围结痂较硬且厚，无法进行剥离。常规治疗同时进行UCMSCs创面周围局部注射治疗。于UCMSCs治疗当天（第0天），距伤口处1 cm范围内注射UCMSCs 1.0×107个；于治疗第3、6天，距创面3 cm处围绕全足注射UCMSCs 1.0×107个；于治疗第9、10天，距创面5 cm处围绕全足注射UCMSCs 1.5×107个；于第15、18天，围绕脚踝处注射UCMSCs 2.0×107个。分别于治疗第1、10、25天，检测患者血常规；于治疗第1、25天，检测患者肝功能和肾功能。于治疗第32、40、46，54、62、70天，对患者进行随访观察。结果　治疗第3天，创面脂肪坏死组织较多，第1跖骨处有向内愈合迹象，但未连接，正常组织暴露仍约有1/5，第3～5跖骨处创面均被坏死组织覆盖，创面周围结痂较硬且厚，无法进行剥离。治疗第12天，第1跖骨处已愈合，第2跖骨处开始向内生长，中间缝隙约有0.5 cm，创面周围出现结痂痕迹，未结痂处开始有向内生长的痕迹，创面后部脓胎较重，异味减轻。治疗第21天，第1跖骨处彻底愈合，第2跖骨处基本愈合，结痂痕迹较之前减弱，未结痂处逐渐向内生长，创面处脓性分泌物和异味进一步减轻。治疗第27天，创面周围结痂基本消失，未结痂处逐渐向内生长明显，创面后部脓性分泌物和异味均较治疗第21天时进一步改善。患者血常规C-反应蛋白水平随着UCMSCs移植呈明显下降趋势；UCMSCs移植对患者肝肾功能无不良影响。结论　UCMSCs可通过抑制炎症、促进肉芽形成以及协助愈后组织重塑、防止瘢痕形成等作用促进糖尿病患者重度DFU创面修复。
Abstract:
Objective　To investigate the effect of umbilical cord mesenchymal stem cells (UCMSCs) transplantation on promoting wound healing of severe diabetic foot ulcer (DFU) and its effect on the function of liver and kidney.Methods　A female patient with DFU who received routine treatment at Department of Wound Treatment,the Second People′s Hospital of Xinxiang in June 2019 was selected as the research subject.On admission,the width and length of the patient′s wound were about 2 cm and 8 cm,the first metatarsal was connected inward,with a distance of about 0.5 cm,and about 1/5 of the normal tissue was exposed.The metatarsal bones from 3rd to 5th were almost covered by necrotic tissue,and the scab around the wound was hard and thick,which could not be dissected.The day of UCMSCs treatment was recorded as day 0 of treatment.At day 0 of treatment,UCMSCs（1.0×107） were injected within 1 cm around the wound;at the 3rd day and 6th day of treatment,UCMSCs (1.0×107) were injected around the whole foot within 3 cm from the wound;at the 9th day and 12th day of treatment,UCMSCs(1.5×107) were injected around the whole foot within 5 cm from the wound;at 15th day and 18th day of treatment,UCMSCs (2.0×107) were injected around the ankle.The routine blood of the patient were detected at the 1st,10th and 25th day of treatment,respectively;the liver and kidney function of the patient were examined at the 1st and 25th day of treatment.The follow-up was performed at the 32th,40th,46th,54th,62th and 70th day of treatment,respectively.Results　At the 3rd day of treatment,there were many adipose necrotic tissues on the wound surface,and signs of inward healing at the first metatarsal bone was observed,but it was not no connected,about 1/5 of the normal tissues were still exposed.The metatarsal bones from 3rd to 5th were almost covered by necrotic tissue,and the scab around the wound was hard and thick,which could not be dissected.At the 12th day of treatment,the first metatarsal was healed,the second metatarsal began to grow inward,and the gap was about 0.5 cm.Scab traces appeared around the wound,and there were signs of ingrown growth in the unscabbed area.The pus was heavier at the back of the wound,and the odor was relieved.At the 21th day of treatment,the first metatarsal healed completely,the second metatarsal almost healed.The scab trace was weakened compared with that before the 21th day of treatment,the unscabbed area gradually grew inward,and the pus and odor at the wound surface were further reduced.At the 27th day of treatment,the scab around the wound almost disappeared,and the unscabbed area grew inward obviously.The pus and peculiar smell at the back of the wound were further improved compared with that at the 21th day of treatment.Simultaneously,the result of routine blood tests showed that the concentration of C-reactive protein had a significant decrease after UCMSCs transplantation;the UCMSCs transplantation have no significant side effect on the liver and kidney functions.Conclusion　UCMSCs treatment can promote wound repair of patient with DFU by inhibiting inflammation,promoting granulation formation and assisting tissue remodeling to prevent scar formation.

参考文献/References:

［1］　SCULLY T.Diabetes in numbers［J］.Nature,2012,485(7398):S2-S3.
［2］　LAVERY L A,DAVIS K E,BERRIMAN S J,et al.WHS guidelines update:diabetic foot ulcer treatment guidelines［J］.Wound Repair Regen,2016,24(1):112-126.
［3］　REKHA P D,RAO S S,SAHANA T G,et al.Diabetic wound management［J］.Br J Community Nurs,2018,23(Sup 9):S16-S22.
［4］　LIM J Z,NG N S,THOMAS C.Prevention and treatment of diabe-tic foot ulcers［J］.J R Soc Med,2017,110(3):104-109.
［5］　DAVIS F M,KIMBALL A,BONIAKOWSKI A,et al.Dysfunctional wound healing in diabetic foot ulcers:new crossroads［J］.Curr Diab Rep,2018,18(1):2.
［6］　BALTZIS D,ELEFTHERIADOU I,VEVES A.Pathogenesis and treatment of impaired wound healing in diabetes mellitus:new insights［J］.Adv Ther,2014,31(8):817-836.
［7］　BANDYK D F.The diabetic foot:pathophysiology,evaluation,and treatment［J］.Semin Vasc Surg,2018,31(2-4):43-48.
［8］　EVERETT E,MATHIOUDAKIS N.Update on management of diabetic foot ulcers［J］.Ann N Y Acad Sci,2018,1411(1):153-165.
［9］　BROCCO E,NINKOVIC S,MARIN M,et al.Diabetic foot management:multidisciplinary approach for advanced lesion rescue［J］.J Cardiovasc Surg (Torino),2018,59(5):670-684.
［10］　BEHNKE J,KREMER S,SHAHZAD T,et al.MSC based therapies-new perspectives for the injured lung［J］.J Clin Med,2020,9(3):682.
［11］　刘彦礼,曹毓琳,林俊堂.经血源子宫内膜干细胞生物学特性及临床应用研究进展［J］.新乡医学院学报,2020,37(9):885-889.
［12］　ROHBAN R,PIEBER T R.Mesenchymal stem and progenitor cells in regeneration:tissue specificity and regenerative potential［J］.Stem Cells Int,2017,2017:5173732.
［13］　FARHADIHOSSEINABADI B,FARAHANI M,TAYEBI T,et al.Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine［J］.Artif Cells Nanomed Biotechnol,2018,46(Suppl 2):431-440.
［14］　CAO Y,GANG X,SUN C,et al.Mesenchymal stem cells improve healing of diabetic foot ulcer［J］.J Diabetes Res,2017,2017:9328374.DOI:10.1155/2017/9328347.
［15］　MIZUKAMI H,YAGIHASHI S.Exploring a new therapy for diabetic polyneuropathy-the application of stem cell transplantation［J］.Front Endocrinol (Lausanne),2014,5:45.
［16］　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.
［17］　GAO F,CHIU S M,MOTAN D A,et al.Mesenchymal stem cells and immunomodulation:current status and future prospects［J］.Cell Death Dis,2016,7(1):e2062.
［18］　BEYTH S,BOROVSKY Z,MEVORACH D,et al.Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness［J］.Blood,2005,105(5):2214-2219.
［19］　AGGA0RWAL S,PITTENGER M F.Human mesenchymal stem cells modulate allogeneic immune cell responses［J］.Blood,2005,105(4):1815-1822.
［20］　SUBRAMMANIYAN R,AMALORPAVANATHAN J,SHANKAR R,et al.Our experience of application of autologous bone marrow stem cells in critical limb ischemia in six diabetic patients-a five-year follow-up［J］.J Stem Cells Regen Med,2011,7(2):97.
［21］　LI X,GAN K,SONG G,et al.VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats［J］.J Diabetes Complications,2015,29(7):872-881.
［22］　ROSSMANITH T,SCHRDER B,BUG G,et al.Interleukin 3 improves the ex vivo expansion of primitive human cord blood progenitor cells and maintains the engraftment potential of scid repopulating cells［J］.Stem Cells,2001,19(4):313-320.
［23］　AMOH Y,HOFFMAN R M.Hair follicle-associated-pluripotent (HAP) stem cells［J］.Cell Cycle,2017,16(22):2169-2175.
［24］　KOSARIC N,KIWANUKA H,GURTNER G C.Stem cell therapies for wound healing［J］.Expert Opin Biol Ther,2019,19(6):575-585.
［25］　EBRAHIMIAN T G,POUZOULET F,SQUIBAN C,et al.Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing［J］.Arterioscler Thromb Vasc Biol,2009,29(4):503-510.
［26］　DAS H,ABDULHAMEED N,JOSEPH M,et al.Ex vivo nanofiber expansion and genetic modification of human cord blood-derived progenitor/stem cells enhances vasculogenesis［J］.Cell Transplant,2009,18(3):305-318.
［27］　MARI W,ALSABRI S G,TABAL N,et al.Novel insights on understanding of keloid scar:article review［J］.J Am Coll Clin Wound Spec,2015,7(1-3):1-7.
［28］　ADAMS K L,GALLO V.The diversity and disparity of the glial scar［J］.Nat Neurosci,2018,21(1):9-15.
［29］　LI M,QIU L,HU W,et al.Genetically-modified bone mesenchymal stem cells with TGF-β3 improve wound healing and reduce scar tissue formation in a rabbit model［J］.Exp Cell Res,2018,367(1):24-29.

相似文献/References:

[1]邢雪琨,武红艳.血清对脐带间充质干细胞体外培养的影响 [J].新乡医学院学报,2012,29(12):896.
[2]邹晓萍,叶豪奕,程　虎,等.脐带间充质干细胞对急性卵巢缺血再灌注损伤小鼠卵巢组织中过氧化物歧化酶及白细胞介素-12表达的影响[J].新乡医学院学报,2019,36(7):601.[doi:10.7683/xxyxyxb.2019.07.001]
　ZOU Xiao-ping,YE Hao-yi,CHENG Hu,et al.Effect of umbilical cord mesenchymal stem cells on the expression of superoxide dismutase and interleukin-12 in ovarian tissues of mice with acute ovarian ischemia reperfusion injury[J].Journal of Xinxiang Medical University,2019,36(7):601.[doi:10.7683/xxyxyxb.2019.07.001]
[3]赵先锋,徐　予,朱中玉,等.脐带间充质干细胞治疗慢性扩张型心肌病合并心力衰竭疗效观察[J].新乡医学院学报,2017,34(9):823.[doi:10.7683/xxyxyxb.2017.09.011]
　ZHAO Xian-feng,XU Yu,ZHU Zhong-yu,et al.Clinical efficacy of umbilical cord mesenchymal stem cells for treatment of chronic dilated cardiomyopathy complicated with systolic heart failure[J].Journal of Xinxiang Medical University,2017,34(7):823.[doi:10.7683/xxyxyxb.2017.09.011]
[4]张刘源,陈贵梅,魏向娟,等.D-核糖交联胶原/纤维蛋白胶复合支架的制备及体外性能研究[J].新乡医学院学报,2016,33(12):1031.[doi:10.7683/xxyxyxb.2016.12.004]
　ZHANG Liu-yuan,CHEN Gui-mei,WEI Xiang-juan,et al.Preparation and characteration in vitro of D-ribose crosslinked collagen /fibrin composite scaffolds[J].Journal of Xinxiang Medical University,2016,33(7):1031.[doi:10.7683/xxyxyxb.2016.12.004]

更新日期/Last Update: 2021-07-05