Effects of stromal cell-derived factor-1 on bone marrow mesenchymal stem cells migration and skin wound repair

doi:10.3969/j.issn.2095-4344.2015.06.005

Abstract

Abstract:

BACKGROUND: Stromal cell-derived factor-1 has a strong chemotaxis to bone marrow mesenchymal stem cells, and both of them can promote wound healing. However, there are less studies on their correlation with skin wound healing.
OBJECTIVE: To investigate the effects of stromal cell-derived factor-1 on bone marrow mesenchymal stem cells migration and skin wound repair.
METHODS: Thirty SD rats were divided into five groups at random. Bone marrow mesenchymal stem cells labeled with PKH-26 were injected into the rat caudal vein. After 1 week, skin wound models were established. Then, different concentrations (1, 2, 10, 50 μg/L) of stromal cell-derived factor-1 were injected via multi-points on the skin wound. The skin wound healing was observed and recorded at 14 days after injection. The number and distribution of bone marrow mesenchymal stem cells were observed by the fluorescent staining at different time points. The pathological changes of wound tissue were observed by hematoxylin-eosin staining. The expression of collagen I and collagen III were detected by western blot assay.
RESULTS AND CONCLUSION: Stromal cell-derived factor-1 at 10 μg/L could induce the largest number of bone marrow mesenchymal stem cells to the skin wound and achieve the best repair results. Stromal cell-derived factor-1 could also regulate the expression of collagen I and collagen III in the wound, and when the concentration
of stromal cell-derived factor-1 was 10 μg/L, the expressions of collagen I and collagen II reached the peak. These findings indicate that the appropriate concentration of stromal cell-derived factor-1 is better to promote the migration of bone marrow mesenchymal stem cells, thereby contributing to skin wound repair.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: Bone Marrow, Mesenchymal Stem Cell Transplantation, Skin, Wounds and Injuries, Chemokine CXCL12, Receptors, CXCR4

CLC Number:

R394.2

Ding Yue, Xu Hai-long, Song Cong-xiao, Sun Xiao-ju. Effects of stromal cell-derived factor-1 on bone marrow mesenchymal stem cells migration and skin wound repair[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(6): 843-848.

Figures/Tables 2

2.1 骨髓间充质干细胞的形态学观察细胞消化传代后呈圆形，接种2.0-3.0 h后即可贴壁生长，渐渐成为长梭形。传代后的细胞增殖比较快，呈均匀分布的纺锤形细胞生长，四五天可传代1次，随着传代次数的增加，细胞生长速度逐渐加快，骨髓间充质干细胞的纯度更高。传至第3代已经得到纯度很高且可以用于后续实验的骨髓间充质干细胞，见图1。 2.2 实验动物数量分析参加实验的SD大鼠30只，进入结果分析为30只，中途无脱落。 2.3 皮肤愈合情况观察 PKH26标记的骨髓间充质干细胞经尾静脉注射后，给予不同浓度的SDF-1进行干预，干预后第14天观察大鼠的皮肤愈合情况。结果显示，SDF-1干预组的皮肤愈合情况比生理盐水组好，其中，SDF-1质量浓度达到10 μg/L时，大鼠的皮肤愈合情况最好，见图2。 2.4 SDF-1干预对骨髓间充质干细胞分布的影响 PKH26标记的骨髓间充质干细胞经尾静脉注射后，给予不同质量浓度的SDF-1进行干预，14 d后处死大鼠，取切口处的全层皮肤组织进行冰冻切片，于荧光显微镜下观察，结果显示，SDF-1干预组切片中的红色荧光数量明显高于生理盐水组，且红色荧光向切口愈合部位迁移。在SDF-1剂量达到10 μg/L时，红色荧光数量最多，见图3。 2.5 皮肤组织切片苏木精-伊红染色结果 SDF-1干预后14 d处死大鼠，取切口处全层皮肤组织进行石蜡切片，然后进行苏木精-伊红染色。结果显示，在创面局部应用外源性SDF-1干预后，SDF-1干预组创面炎症反应比生理盐水组轻，创面厚度也较生理盐水组薄，SDF-1的质量浓度达到10 μg/L时，创面炎症反应最轻，创面厚度最薄，见图4。 2.6 Western blot检测皮肤创伤组织Ⅰ型胶原及Ⅲ型胶原表达 Western blot结果显示，SDF-1干预组Ⅰ型和Ⅲ型胶原的表达明显高于生理盐水对照组，在SDF-1的剂量达到10 μg/L时，Ⅰ型和Ⅲ型胶原的表达最高，见图5。 "

References

[1] Eming SA, Martin P, Tomic-Canic M.Wound repair and regeneration: mechanisms, signaling, and translation.Sci Transl Med. 2014;6(265):265-266.
[2] You HJ, Han SK.Cell therapy for wound healing.J Korean Med Sci. 2014;29(3):311-319.
[3] Peng LH, Mao ZY, Qi XT,et al.Transplantation of bone-marrow-derived mesenchymal and epidermal stem cells contribute to wound healing with different regenerative features.Cell Tissue Res. 2013;352(3):573-583.
[4] Xue L, Xu YB, Xie JL, et al. Effects of human bone marrow mesenchymal stem cells on burn injury healing in a mouse model.Int J Clin Exp Pathol. 2013;6(7):1327-1336.
[5] Luo Q, Zhang C, Song G. Research progresses of paracrine effect of bone marrow derived mesenchymal stem cells on wound healing. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2012;29(5):999-1002.
[6] Jin Q, Giannobile WV.SDF-1 enhances wound healing of critical-sized calvarial defects beyond self-repair capacity. PLoS One. 2014;9(5):e97035.
[7] Chen X, Zhu YJ, Han LL,et al. Chemokine receptor 4 gene silencing blocks neuroblastoma metastasis in vitro. Neural Regen Res. 2014;9(10): 1063-1067.
[8] Yu J, Li M, Qu Z, et al. SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt.J Cardiovasc Pharmacol. 2010;55(5):496-505.
[9] Kitaori T, Ito H, Schwarz EM, et al. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model.Arthritis Rheum. 2009;60(3): 813-823.
[10] Ding J, Hori K, Zhang R,et al. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in the formation of postburn hypertrophic scar (HTS).Wound Repair Regen. 2011;19(5): 568-578.
[11] Gillitzer R, Goebeler M.Chemokines in cutaneous wound healing.J Leukoc Biol. 2001;69(4):513-521.
[12] Mescher AL, Neff AW.Regenerative capacity and the developing immune system.Adv Biochem Eng Biotechnol. 2005;93:39-66.
[13] Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.Nat Med. 2004;10(8):858-864.
[14] Shiba Y, Takahashi M, Yoshioka T, et al. M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system. Arterioscler Thromb Vasc Biol. 2007;27(2):283-289.
[15] Martins-Green M, Petreaca M, Wang L.Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing.Adv Wound Care (New Rochelle). 2013;2(7):327-347.
[16] Delorme B, Chateauvieux S, Charbord P.The concept of mesenchymal stem cells. Regen Med. 2006;1(4):497-509.
[17] Wang Y, Deng Y, Zhou GQ. SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res. 2008;1195:104-112.
[18] Gong J, Meng HB, Hua J, et al. The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis. Mol Med Rep. 2014;9(5):1575-1582.
[19] Honczarenko M, Le Y, Swierkowski M, et al. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors.Stem Cells. 2006;24(4): 1030-1041.
[20] Brenner S, Whiting-Theobald N, Kawai T, et al. CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells.Stem Cells. 2004;22(7):1128-1133.
[21] Wynn RF, Hart CA, Corradi-Perini C,et al.A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow.Blood. 2004;104(9):2643-2645.
[22] McFarlin K, Gao X, Liu YB, et al. Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat.Wound Repair Regen. 2006;14(4):471-478.
[23] Tang YL, Qian K, Zhang YC, et al. Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid mediated stromal-cell-derived factor-1alpha (SDF-1alpha) treatment. Regul Pept. 2005;125(1-3):1-8.
[24] Kucia M, Wojakowski W, Reca R,et al. The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner.Arch Immunol Ther Exp (Warsz). 2006;54(2): 121-135.
[25] Tögel F, Isaac J, Hu Z, et al. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury.Kidney Int. 2005;67(5):1772-1784.
[26] Guo R, Chai L, Chen L, et al. Stromal cell-derived factor 1 (SDF-1) accelerated skin wound healing by promoting the migration and proliferation of epidermal stem cells.In Vitro Cell Dev Biol Anim. 2015. [Epub ahead of print]
[27] Grabska-Liberek I, Galus R, Owczarek W, et al. Collagen based dressings in the treatment of wound healing.Pol Merkur Lekarski. 2013;35(205):51-54.
[28] Cuttle L, Nataatmadja M, Fraser JF, et al. Collagen in the scarless fetal skin wound: detection with picrosirius- polarization.Wound Repair Regen. 2005;13(2):198-204.
[29] Zgheib C, Xu J, Liechty KW. Targeting Inflammatory Cytokines and Extracellular Matrix Composition to Promote Wound Regeneration. Adv Wound Care (New Rochelle). 2014;3(4):344-355.
[30] Upadhyay A, Chattopadhyay P, Goyary D, et al. Eleutherine indica L. accelerates in vivo cutaneous wound healing by stimulating Smad-mediated collagen production.J Ethnopharmacol. 2013;146(2):490-494.
[31] Isackson D, Cook KJ, McGill LD, et al. Mesenchymal stem cells increase collagen infiltration and improve wound healing response to porous titanium percutaneous implants. Med Eng Phys. 2013;35(6):743-753.