Security of heterogeneous umbilical cord mesenchymal stem cells via intramuscular injection in Wistar rats

doi:10.3969/j.issn.2095-4344.2014.41.011

Abstract

Abstract:

BACKGROUND: So far, the short-term changes of various organs after injection of umbilical cord mesenchymal stem cells have been reported, but there are few studies on the long-term changes of various organs in healthy rats after repeated intramuscular injection of umbilical cord mesenchymal stem cells.

OBJECTIVE: To observe the security of intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells.

METHODS: Sixty male SPF Wistar rats were divided into six groups randomly: normal group (suspension liquid of umbilical cord mesenchymal stem cells); control group with culture solution; supernatant group (supernatant of human umbilical cord mesenchymal stem cells); low concentration group (0.25×10⁵ human umbilical cord mesenchymal stem cells); moderate concentration group (1.0×10⁵ human umbilical cord mesenchymal stem cells); high concentration group (4.0×10⁵ human umbilical cord mesenchymal stem cells). Each rat was injected 0.8 mL liquid in muscle, 0.2 mL in each limb, twice at weeks 1 and 4. Biochemical tests were conducted before and after injection. At the end of 8 weeks, all the rats were killed and hematoxylin-eosin staining was done with the liver, spleen, lung, kidney, brain and muscle.
RESULTS AND CONCLUSION: There was no abnormal change about biochemical tests and hematoxylin-eosin staining after the intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells. No significant alteration was observed in the liver, spleen, lung, kidney, brain, and muscle of the limb after the injection of heterogeneous umbilical cord mesenchymal stem cells under suitable concentration. These findings indicate intramuscular injection of heterogeneous umbilical cord mesenchymal stem cells at certain concentrations is safe and reliable.

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: umbilical cord, mesenchymal stem cell transplantation, injections, intramuscular, safety

CLC Number:

R394.2

Zhang Wen-xiang, Wang Si-ping, Xi Hong-min, Li Zi-pu. Security of heterogeneous umbilical cord mesenchymal stem cells via intramuscular injection in Wistar rats[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(41): 6620-6627.

Figures/Tables 4

References

[1] Barry FP, Murphy JM.Mesenchymal stem cells: clinical applications and biological characterization.Int J Biochem Cell Biol. 2004;36(4):568-584.
[2] Fang B, Shi M, Liao L,et al.Multiorgan engraftment and multilineage differentiation by human fetal bone marrow Flk1+/CD31-/CD34- Progenitors.J Hematother Stem Cell Res. 2003;12(6):603-613.
[3] Fang B, Liao L, Shi M,et al.Multipotency of Flk1CD34 progenitors derived from human fetal bone marrow.J Lab Clin Med. 2004;143(4):230-240.
[4] Jiang Y, Jahagirdar BN, Reinhardt RL,et al.Pluripotency of mesenchymal stem cells derived from adult marrow.Nature. 2002;418(6893):41-49.
[5] Schwartz RE, Reyes M, Koodie L,et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells.J Clin Invest. 2002;109(10):1291-1302.
[6] 张学峰,张美荣,胡建霞,等.异种脐带间充质干细胞静脉应用的安全性[J].中国组织工程研究与临床康复,2010,14(32): 5971-5975.
[7] 张美荣,张学峰,胡建霞,等.大鼠肌肉注射移植人脐带间充质干细胞的安全性[J].中国组织工程研究与临床康复,2010,14(27): 4997-5000.
[8] Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells.J Embryol Exp Morphol. 1966;16(3):381-390.
[9] Pittenger MF, Mackay AM, Beck SC,et al.Multilineage potential of adult human mesenchymal stem cells.Science. 1999;284(5411):143-147.
[10] 肖娟,姜晓蓉,刘靖媛,等.脐带间充质细胞生物学特性及应用研究[J].解剖科学进展,2013,19(4):363-365.
[11] Wang Y, Huso DL, Harrington J,et al.Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture.Cytotherapy. 2005;7(6): 509-519.
[12] Bochkov NP, Voronina ES, Kosyakova NV,et al.Chromosome variability of human multipotent mesenchymal stromal cells. Bull Exp Biol Med. 2007;143(1):122-126.
[13] Jeong JO, Han JW, Kim JM,et al.Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy.Circ Res. 2011;108(11):1340-1347.
[14] Medicetty S, Bledsoe AR, Fahrenholtz CB,et al.Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks.Exp Neurol. 2004;190(1):32-41.
[15] Weiss ML, Mitchell KE, Hix JE,et al.Transplantation of porcine umbilical cord matrix cells into the rat brain.Exp Neurol. 2003; 182(2):288-299.
[16] Pirtskhalaishvili G, Shurin GV, Gambotto A,et al.Transduction of dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice.J Immunol. 2000;165(4):1956-1964.
[17] Ludewig B, Graf D, Gelderblom HR,et al.Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10.Eur J Immunol. 1995;25(7):1943-1950.
[18] 何君,李洋,陈威,等.人脐带间充质干细胞静脉输注小鼠的安全性[J].中国比较医学杂志,2013,23(9):36-41.
[19] Kinnaird T, Stabile E, Burnett MS,et al.Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.Circ Res. 2004;94(5):678-685.
[20] Casillas-Ramírez A, Zaouali A, Padrissa-Altés S,et al. Insulin-like growth factor and epidermal growth factor treatment: new approaches to protecting steatotic livers against ischemia-reperfusion injury.Endocrinology. 2009; 150(7):3153-3161.
[21] Gnecchi M, He H, Noiseux N,et al.Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661-669.
[22] Tang YL, Zhao Q, Qin X,et al.Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg. 2005;80(1):229-236.
[23] 张颖,李娜,辛毅,等.大鼠静脉注射人脐带胶样组织来源间充质干细胞的安全性研究[J].心肺血管病杂志,2013,32(6):783-788.
[24] Fazel S, Chen L, Weisel RD,et al.Cell transplantation preserves cardiac function after infarction by infarct stabilization: augmentation by stem cell factor.J Thorac Cardiovasc Surg. 2005;130(5):1310.
[25] Burt RK, Loh Y, Pearce W,et al.Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases.JAMA. 2008;299(8):925-936.
[26] Toma C, Pittenger MF, Cahill KS,et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart.Circulation. 2002;105(1):93-98.
[27] Dai W, Hale SL, Martin BJ,et al.Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects.Circulation. 2005;112(2):214-223.
[28] Lee H, Bae JS, Jin HK.Human umbilical cord blood-derived mesenchymal stem cells improve neurological abnormalities of Niemann-Pick type C mouse by modulation of neuroinflammatory condition.J Vet Med Sci. 2010;72(6): 709-717.
[29] Phinney DG, Prockop DJ.Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views.Stem Cells. 2007; 25(11):2896-2902.
[30] 陈晓岚,黄仁彬,汤银娟,等.人脐血间充质干细胞静脉移植治疗大鼠局灶性脑缺血的实验研究[J].中国实用神经疾病杂志,2007, 10(1):4-7.
[31] Burt RK, Loh Y, Pearce W,et al.Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases.JAMA. 2008;299(8):925-936.
[32] Hare JM.Translational development of mesenchymal stem cell therapy for cardiovascular diseases.Tex Heart Inst J. 2009;36(2):145-147.
[33] Li DH,Wang CH,Shan W,et al. Human amnion tissue injected with human umbilical cord mesenchymal stem cells repairs damaged sciatic nerves in rats. Neural Regen Res.2012;7(23): 1771-1778.
[34] Li Z, Qin HJ, Feng ZS, et al. Human umbilical cord mesenchymal stem cell- loaded amniotic membrane for the repair of radial nerve injury. Neural Regen Res.2013; 8(36): 3441-3448.
[35] Koç ON, Gerson SL, Cooper BW,et al.Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307-316.