Potential Therapeutic Effect of Paracrine Factors from Bone Marrow-derived Mesenchyme Stem Cells in the Treatment of Severe Acute Pancreatitis_Journal of Biomedical Engineering

Authors：

CHENKeling , ZHOUZongguang , ZHOUBin ,  LIYuan

Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LIYuan, Email: liyuanletters@163.com

Keywords：

serve acute pancreatitis; bone marrow-derived mesenchymal stem cells; paracrine factors

DOI：

10.7507/1001-5515.20150045

Video：

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Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is one of the most popular therapeutic measures in severe acute pancreatitis (SAP). However, technical challenges and ethical concern have hindered its clinical application. Paracrine factor, as a new safe and easy handing therapeutic measure, can work comparably effective as BMSC transplantation in SAP therapy, but bio-safe risks could be greatly reduced. In this paper, we reviewed the therapeutic effect and potential mechanism of paracrine factors in the treatment of SAP. The injection of paracrine factors yielded from cultured cell suspension will be a new cell therapeutic measure for SAP.

Citation： CHENKeling, ZHOUZongguang, ZHOUBin, LIYuan. Potential Therapeutic Effect of Paracrine Factors from Bone Marrow-derived Mesenchyme Stem Cells in the Treatment of Severe Acute Pancreatitis. Journal of Biomedical Engineering, 2015, 32(1): 245-248. doi: 10.7507/1001-5515.20150045 Copy

1.	BURDON T J, PAUL A, NOISEUX N, et al. Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential[J]. Bone Marrow Res, 2011, 2011: 207326.
2.	罗庆, 张晨, 宋关斌.骨髓间充质干细胞旁分泌作用在组织损伤修复中的研究进展[J].生物医学工程学杂志, 2012, 29(5): 999-1002.
3.	WILLIAMS A R, HARE J M. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease[J]. Circ Res, 2011, 109(8): 923-940.
4.	KAGAMI H, AGATA H, TOJO A. Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for bone tissue engineering: basic science to clinical translation[J]. Int J Biochem Cell Biol, 2011, 43(3): 286-289.
5.	BERNARDO M E, FIBBE W E. Safety and efficacy of mesenchymal stromal cell therapy in autoimmune disorders[J]. Ann N Y Acad Sci, 2012, 1266: 107-117.
6.	郭子宽.间充质干细胞及其临床应用中的几个问题[J].中国组织工程研究, 2012, 16(1): 1-10.
7.	AKRAM K M, SAMAD S, SPITERI M A, et al. Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms[J]. Respir Res, 2013, 14(1): 9.
8.	IONESCU L, BYRNE R N, VAN HAAFTEN T, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 303(11): L967-L977.
9.	LEE J W, FANG Xiaohui, KRASNODEMBSKAYA A, et al. Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors[J]. Stem Cells, 2011, 29(6): 913-919.
10.	AMOS P J, MULVEY C L, SEAMAN S A, et al. Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells[J]. Am J Physiol Cell Physiol, 2011, 301(6): C1378-C1388.
11.	ZENG Dongfeng, LIU Ting, CHANG Cheng, et al. Silencing HIF-1αreduces the adhesion and secretion functions of acute leukemia hBMSCs[J]. Braz J Med Biol Res, 2012, 45(10): 906-912.
12.	KYLÄNPÄÄ L, RAKONCZAY Z Jr, O'REILLY D A. The clinical course of acute pancreatitis and the inflammatory mediators that drive it[J]. Int J Inflam, 2012, 2012: 360685.
13.	JUNG K H, SONG S U, YI T, et al. Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats[J]. Gastroenterology, 2011, 140(3): 998-1008.
14.	WANG Lie, TU Xiaohuang, ZHAO Peng, et al. Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats[J]. Mol Med Rep, 2012, 6(2): 287-292.
15.	WU Qiaoyi, WANG Feng, HOU Yuling, et al. The effect of allogenetic bone marrow-derived mesenchymal stem cell transplantation on lung aquaporin-1 and-5 in a rat model of severe acute pancreatitis[J]. Hepatogastroenterology, 2012, 59(116): 965-976.
16.	TU Xiaohuang, SONG Jingxiang, XUE Xiaojun, et al. Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis[J]. World J Gastroenterol, 2012, 18(18): 2270-2279.
17.	盛闽, 陈志耀, 黄鹤光, 等.同种异体骨髓间充质干细胞移植治疗重症急性胰腺炎相关肺损伤[J].中国组织工程研究, 2012, 16(36): 6702-6709.
18.	BONNER-WEIR S, INADA A, YATOH S, et al. Transdifferentiation of pancreatic ductal cells to endocrine beta-cells[J]. Biochem Soc Trans, 2008, 36(Pt 3): 353-356.
19.	DOR Y, BROWN J, MARTINEZ O I, et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation[J]. Nature, 2004, 429(6987): 41-46.
20.	QIN Zhaohui, XU Jinfu, QU Jieming, et al. Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism[J]. J Cell Mol Med, 2012, 16(11): 2745-2753.
21.	YAGI H, SOTO-GUTIERREZ A, NAVARRO-ALVAREZ N, et al. Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1[J]. Mol Ther, 2010, 18(10): 1857-1864.
22.	ZHAO Manman, CUI Jianzhong, CUI Ying, et al. Therapeutic effect of exogenous bone marrow-derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats[J]. Mol Med Rep, 2013, 8(3): 741-746.
23.	李德泉, 黄跃跃, 潘景业, 等.骨髓间充质干细胞对重症急性胰腺炎大鼠肺组织的保护作用及其机制[J].中华实验外科杂志, 2011, 28(12): 2252-2253.
24.	YI T, SONG S U. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications[J]. Arch Pharm Res, 2012, 35(2): 213-221.
25.	XU Xiang, ZHU Fangqiang, ZHANG Meng, et al. Stromal cell-derived factor-1 enhances wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area and promoting neovascularization[J]. Cells Tissues Organs, 2013, 197(2): 103-113.
26.	REIS L A, BORGES F T, SIMÕES M J, et al. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats[J]. PLoS One, 2012, 7(9): e44092.
27.	LIU Nanmei, PATZAK A, ZHANG Jinyuan. CXCR4-overexpressing bone marrow-derived mesenchymal stem cells improve repair of acute kidney injury[J]. Am J Physiol Renal Physiol, 2013, 305(7): F1064-F1073.
28.	BINATO R, DE SOUZA FERNANDEZ T, LAZZAROTTO-SILVA C, et al. Stability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy[J]. Cell Prolif, 2013, 46(1): 10-22.
29.	WASZAK P, ALPHONSE R, VADIVEL A, et al. Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats[J]. Stem Cells Dev, 2012, 21(15): 2789-2797.
30.	LI M, TILLES A W, MILWID J M, et al. Phenotypic and functional characterization of human bone marrow stromal cells in hollow-fibre bioreactors[J]. J Tissue Eng Regen Med, 2012, 6(5): 369-377.

1. BURDON T J, PAUL A, NOISEUX N, et al. Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential[J]. Bone Marrow Res, 2011, 2011: 207326.
2. 罗庆, 张晨, 宋关斌.骨髓间充质干细胞旁分泌作用在组织损伤修复中的研究进展[J].生物医学工程学杂志, 2012, 29(5): 999-1002.
3. WILLIAMS A R, HARE J M. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease[J]. Circ Res, 2011, 109(8): 923-940.
4. KAGAMI H, AGATA H, TOJO A. Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for bone tissue engineering: basic science to clinical translation[J]. Int J Biochem Cell Biol, 2011, 43(3): 286-289.
5. BERNARDO M E, FIBBE W E. Safety and efficacy of mesenchymal stromal cell therapy in autoimmune disorders[J]. Ann N Y Acad Sci, 2012, 1266: 107-117.
6. 郭子宽.间充质干细胞及其临床应用中的几个问题[J].中国组织工程研究, 2012, 16(1): 1-10.
7. AKRAM K M, SAMAD S, SPITERI M A, et al. Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms[J]. Respir Res, 2013, 14(1): 9.
8. IONESCU L, BYRNE R N, VAN HAAFTEN T, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 303(11): L967-L977.
9. LEE J W, FANG Xiaohui, KRASNODEMBSKAYA A, et al. Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors[J]. Stem Cells, 2011, 29(6): 913-919.
10. AMOS P J, MULVEY C L, SEAMAN S A, et al. Hypoxic culture and in vivo inflammatory environments affect the assumption of pericyte characteristics by human adipose and bone marrow progenitor cells[J]. Am J Physiol Cell Physiol, 2011, 301(6): C1378-C1388.
11. ZENG Dongfeng, LIU Ting, CHANG Cheng, et al. Silencing HIF-1αreduces the adhesion and secretion functions of acute leukemia hBMSCs[J]. Braz J Med Biol Res, 2012, 45(10): 906-912.
12. KYLÄNPÄÄ L, RAKONCZAY Z Jr, O'REILLY D A. The clinical course of acute pancreatitis and the inflammatory mediators that drive it[J]. Int J Inflam, 2012, 2012: 360685.
13. JUNG K H, SONG S U, YI T, et al. Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats[J]. Gastroenterology, 2011, 140(3): 998-1008.
14. WANG Lie, TU Xiaohuang, ZHAO Peng, et al. Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats[J]. Mol Med Rep, 2012, 6(2): 287-292.
15. WU Qiaoyi, WANG Feng, HOU Yuling, et al. The effect of allogenetic bone marrow-derived mesenchymal stem cell transplantation on lung aquaporin-1 and-5 in a rat model of severe acute pancreatitis[J]. Hepatogastroenterology, 2012, 59(116): 965-976.
16. TU Xiaohuang, SONG Jingxiang, XUE Xiaojun, et al. Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis[J]. World J Gastroenterol, 2012, 18(18): 2270-2279.
17. 盛闽, 陈志耀, 黄鹤光, 等.同种异体骨髓间充质干细胞移植治疗重症急性胰腺炎相关肺损伤[J].中国组织工程研究, 2012, 16(36): 6702-6709.
18. BONNER-WEIR S, INADA A, YATOH S, et al. Transdifferentiation of pancreatic ductal cells to endocrine beta-cells[J]. Biochem Soc Trans, 2008, 36(Pt 3): 353-356.
19. DOR Y, BROWN J, MARTINEZ O I, et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation[J]. Nature, 2004, 429(6987): 41-46.
20. QIN Zhaohui, XU Jinfu, QU Jieming, et al. Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism[J]. J Cell Mol Med, 2012, 16(11): 2745-2753.
21. YAGI H, SOTO-GUTIERREZ A, NAVARRO-ALVAREZ N, et al. Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1[J]. Mol Ther, 2010, 18(10): 1857-1864.
22. ZHAO Manman, CUI Jianzhong, CUI Ying, et al. Therapeutic effect of exogenous bone marrow-derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats[J]. Mol Med Rep, 2013, 8(3): 741-746.
23. 李德泉, 黄跃跃, 潘景业, 等.骨髓间充质干细胞对重症急性胰腺炎大鼠肺组织的保护作用及其机制[J].中华实验外科杂志, 2011, 28(12): 2252-2253.
24. YI T, SONG S U. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications[J]. Arch Pharm Res, 2012, 35(2): 213-221.
25. XU Xiang, ZHU Fangqiang, ZHANG Meng, et al. Stromal cell-derived factor-1 enhances wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area and promoting neovascularization[J]. Cells Tissues Organs, 2013, 197(2): 103-113.
26. REIS L A, BORGES F T, SIMÕES M J, et al. Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats[J]. PLoS One, 2012, 7(9): e44092.
27. LIU Nanmei, PATZAK A, ZHANG Jinyuan. CXCR4-overexpressing bone marrow-derived mesenchymal stem cells improve repair of acute kidney injury[J]. Am J Physiol Renal Physiol, 2013, 305(7): F1064-F1073.
28. BINATO R, DE SOUZA FERNANDEZ T, LAZZAROTTO-SILVA C, et al. Stability of human mesenchymal stem cells during in vitro culture: considerations for cell therapy[J]. Cell Prolif, 2013, 46(1): 10-22.
29. WASZAK P, ALPHONSE R, VADIVEL A, et al. Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats[J]. Stem Cells Dev, 2012, 21(15): 2789-2797.
30. LI M, TILLES A W, MILWID J M, et al. Phenotypic and functional characterization of human bone marrow stromal cells in hollow-fibre bioreactors[J]. J Tissue Eng Regen Med, 2012, 6(5): 369-377.

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Potential Therapeutic Effect of Paracrine Factors from Bone Marrow-derived Mesenchyme Stem Cells in the Treatment of Severe Acute Pancreatitis

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