Activin B联合BMSCs不同移植方式对大鼠皮肤创伤愈合的治疗

中国临床解剖学杂志 ›› 2012, Vol. 30 ›› Issue (2): 197-202.

Activin B联合BMSCs不同移植方式对大鼠皮肤创伤愈合的治疗

孙　丽¹，　王雪儿¹，　张敏¹，　陈世萱¹，　孔亚男¹，　崔梦卿²，　张　璐³，　张　琳¹

南方医科大学　1.组织胚胎学教研室； 2.门诊部；　3.病理生理学教研室，广州 510515

收稿日期:2011-11-20 出版日期:2012-03-25 发布日期:2012-04-17
通讯作者: 张琳，教授，博士生导师，Tel：(020)61648205，E-mail:zlilyzh@126.com E-mail:651306521@qq.com
作者简介:孙丽 (1981-)，女，河南汝州，博士，干细胞信号转导机制研究，Tel：(020)62789373
基金资助:
国家自然科学基金（81171824，30973129）；教育部新世纪优秀人才支持计划（NCET-08-0647）；广东省科技攻关项目(2009A030200015)；粤港关键领域重点突破项目（2011A011304001）；广东省产学研合作重大科技专项（2011A090100025）

The treatment of skin wound healing of rats by different transplantation approaches of BMSCs combination with Activin B

SUN Li¹,WANG Xue-er¹, ZHANG Min¹, CHEN Shi-xuan¹, KONG Ya-nan¹, CUI Meng-qing², ZHANG Lu³ ,ZHANG Lin¹

1.Department of Histology and Embryology, Southern Medical University, Guangzhou 510515,China; 2. Outpatient Clinic, Southern Medical University, Guangzhou 510515, China; 3.Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China

Received:2011-11-20 Online:2012-03-25 Published:2012-04-17

摘要/Abstract

摘要：

目的　探讨BMSCs联合生长因子对治疗皮肤创伤最为有效的移植途径。方法　分离并鉴定BMSCs，移植后活体成像仪及冰冻切片观察CFSE标记的BMSCs，统计创面愈合率，并进行HE染色观察伤口愈合。结果　细胞表面标记物CD90表达呈阳性，CD80表达呈阴性。活体成像仪3、7d观察实验组大鼠皮肤创面均有荧光显示，而对照组无。术后各时间点BMSCs移植组创面愈合率均高于对照组（P＜0.05），而不同移植方式相比差异无统计学意义。结论　Activin B联合BMSCs经表皮移植和尾静脉移植均可以迁移至皮肤创伤部位并参与皮肤创伤的修复，相对于尾静脉移植组，表皮移植组在创伤修复中更简便易行。

关键词: 骨髓间充质干细胞, 移植途径, 创伤愈合

Abstract:

Objective　To discuss the optimum transplantation approaches of BMSCs combination with Activin B on skin wound healing.　Methods　BMSCs were identified by immunocytochemistry. Residual situation of the CFSE-labeled BMSCs after transplantation was detected by the In Vivo imaging system and frozen section. Wounded areas were recorded and wound healing was observed by the paraffin section and HE staining.　Results　Positive expression of CD90 and negative expression of CD80 were observed by immunocytochemistry. Fluorescence of the wounded sites of rats in the experimental groups was observed by In vivo imaging system, but it didn't be observed in control group at the 7 and 14 days after skin wounding. Wound healing rate in the experimental group was increased in comparison with that in the control group (P<0.05), but wound healing rate in the different transplantation approaches had no significant difference.　Conclusions　BMSCs transplantation via the epidermal and the tail vein can both migrate to the wounded sites and promote the wound healing. Compared with the tail vein transplantation group, wound repair in the epidermal transplantation group was more simple and feasible.

Key words: BMSCs, Transplantation approach, Wound healing

中图分类号:

孙丽, 王雪儿, 张敏, 陈世萱, 孔亚男, 崔梦卿, 张璐, 张琳. Activin B联合BMSCs不同移植方式对大鼠皮肤创伤愈合的治疗[J]. 中国临床解剖学杂志, 2012, 30(2): 197-202.

SUN Li, WANG Xue-Er, ZHANG Min, CHEN Shi-Xuan, KONG E-Nan, CUI Meng-Qing, ZHANG Lu, ZHANG Lin. The treatment of skin wound healing of rats by different transplantation approaches of BMSCs combination with Activin B[J]. Chinese Journal Of Clinical Anatomy, 2012, 30(2): 197-202.

参考文献

[1] Nakagawa H,Akita S,Fukui M,et al. Human mesenchymal stem cells successfully improve skin-substitute wound healing
[J].Br J Dermatol,2005,153(1):29-36.

[2] Santoro MM, Gaudino G. Cellular and molecular facets of keratinocyte reepithelization during wound healing
[J].Exp Cell Res, 2005, 304(1):274-286.

[3] Min Zhang, Nu-Yun Liu, Lin Zhang, et al. Activin B Promotes Epithelial Wound Healing In Vivo through RhoA-JNK Signaling Pathway
[J].Plos one,2011,6(9): e25143.

[4] Perin EC, Silva GV, Assad JA, et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction
[J].J Mol Cell Cardiol, 2008, 44(3):486-495.

[5] Kuo TK, Hung S, Chuang C, et al. Stem cell therapy for liver disease:parameters governing the success of using bone marrow mesenchymal stem cells
[J].Gastroenterology,2008,134(7):2111-2121.

[6] Behr L, Hekmati M, Fromont G, et al. Intrarenal arterial injection of autologous mesenchymal stemcell in an ovine model in the postischemic kidney
[J].Nephron Physiol, 2007, 107(3):65-76.

[7] Sun JH, Teng GJ ,Ma ZL, et al. In vivo monitoring of magnetically labeled mesenchymal sten cells administered intravascularly in rat acute renal failure
[J].Swiss Med Wkly, 2008, 138(27-28):404-412.

[8] 李庆林，肖能堪，张琳. 探讨ActivinB在皮肤创伤愈合中的作用
[J]. 热带医学杂志，2008, 8(6)：544-547.

[9] Martin P. Wound healing–aiming for perfect skin regeneration
[J]. Science, 1997, 276: 75-81.

[10]Schachinger V, Erbs S, Elsasser A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction
[J].N Engl J Med, 2006, 355(12):1210-1221.

[11] Dohmann HF, Perin EC, Takiya CM, et al. Transendocardial autologous bone marrow mononuclear cell injection in ischemic heart failure:postmortem anatomicopathologic and immunohistochemical findings
[J].Circulation, 2005, 112(4):521-526.

[12]Wang T, Tang W, Sun S, et al. Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia
[J].Crit Care Med, 2007, 35(11):2587-2593.

[13]Bang OY, Lee JS, Lee PH, et al. Autologous mesenchymal stem cell transplantation in stroke patients
[J].Ann Neurol,2005,57(6):874-882.

[14] Mahmood A,Lu D,Wang L,et al.Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury
[J].J Neurotrauma,2002,19(12):1609-1617.

[15] Kassis I, Grigoriadis N, Gowda-Kurkalli B, et al. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis
[J].Arch Neurol,2008,65(6):753-761.

[16]Pacini S,Spinabella S,Trombi L,et al.Suspension of bone marrow-　derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses
[J].Tissue Eng,2007,13(12):2949-2955.

[17]Horwitz EM,Gordon PL.Koo WK,et al.Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta:Implications for cell therapy of bone
[J].Proc Natl Acad Sci USA,2002,99(13):8932-8937.

[18] Abdel Aziz MT,Atta HM,Mahfouz S,et al.Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis
[J].Clin Biochem,2007,40(12):893-899.

[19]Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
[J].Blood,2005,106(2):756-763.

[20]Miyazaki M,Hardjo M,Masaka T,et al.Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for prevention acute fatal liver failure
[J].Stem Cells,2007,25(11):2855-2863.

[21]Barbash OM,Chouraqui P,Baron J,et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infracted myocardium:Feasibility,cell migration,and body distribution
[J].Circulation,2003,108(7):863-868.

[22] Li F, Wang X, Niyibizi C. Distribution of single-cell expanded marrow derived progenitors in a developing mous model of osteogenesis imperfecta following systemic transplantation
[J].Stem Cells,2007,25(12):3183-3193.