Systemic and ocular transplantation of human umbilical cord mesenchymal stem cells into rats with diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

BiXue ,  ChenSong , LinJinyong , 王玉川

Ophthalmology Clinical College of Tianjin Medical University, Tianjin Eye Hospital, Tianjin Institute of Ophthalmology, Tianjin 300020, China;

Corresponding author：

ChenSong, Email: chensong20@hotmail.com

Keywords：

Diabetic retinopathy/therapy; Mesenchymal stem cell transplantation/methods; Brain-derived neurotrophic factor

DOI：

10.3760/cma.j.issn.1005-1015.2014.02.012

Video：

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Objective To observe the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on blood glucose levels and diabetic retinopathy in diabetes mellitus (DM) rats. Method A total of 45 healthy male Sprague-Dawley rats were randomly divided into normal control group (group A, 10 rats) and DM group (33 rats). Diabetic model was established in DM group by tail vein injection of streptozotocin.The DM group was further randomly divided into 3 groups (11 rats in each group), including group B (no transplantation), group C (hUCMSC was injected through tail vein) and group D (hUCMSC was injected into the vitreous). Blood glucose, retina wholemont staining and expression of brain derived neurotrophic factor (BDNF) in the retina were measured at 2, 4, 6, 8 weeks after hUCMSC injection. The blood glucose was significantly different between A-D groups before injection (t=-64.400, -60.601, -44.065, -43.872; P=0.000) BDNF expression was studied by real time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry staining. Results The blood glucose was significantly different between A-D groups after hUCMSC injection (F=400.017, 404.410, 422.043, 344.109; P=0.000), and between group C and group B/D (t=4.447, 4.990; P < 0.01). Immuno-staining shown that BDNF was positive in ganglion cell layer (RGC) of group A, weak in group B while BDNF expression increased in group C/D. BDNF mRNA expression was significantly different between group B, C and D at 4, 6 and 8 weeks after hUCMSC injection (F=29.372, 188.492, 421.537; P=0.000), and between group B and C/D (t=66.781, 72.401, 63.880, 88.423, 75.120, 83.002; P < 0.01) by RT-PCR analysis. The BDNF mRNA expression was significantly different between C and D groups only at 8 weeks after hUCMSC injection (t=127.321, P=0.005). Conclusions Tail vein injection of hUCMSCs can significantly reduce the blood glucose levels of rats. Intravenous and intravitreal injection of hUCMSCs can increase the expression of BDNF.

Citation： BiXue, ChenSong, LinJinyong. Systemic and ocular transplantation of human umbilical cord mesenchymal stem cells into rats with diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2014, 30(2): 166-170. doi: 10.3760/cma.j.issn.1005-1015.2014.02.012 Copy

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13.	Scalinci SZ, Scorolli L, Corradetti G, et al. Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes:neuroprotective growth factors in the vitreous[J].Clin Ophthalmol, 2011, 5:691-696.
14.	Fujieda H, Sasaki H. Expression of brain-derived neurotrophic factor in cholinergic and dopaminergic amacrine cells in the rat retina and the effects of constant light rearing[J].Exp Eye Res, 2008, 86:335-343.
15.	Clarke DB, Wang YC, Bray GM, et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells[J]. Proc Natl Acad Sci USA, 1994, 91:1632-1636.
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1. Antonetti DA, Barber AJ, Bronson SK, et al. Diabetic retinopathy:seeing beyond glucose-induced microvascular disease[J].Diabetes, 2006, 55:2401-2411.
2. Resnikoff S, Pascolini D, Etya'ale D, et al. Global data on visual impairment in the year 2002[J]. Bull World Health Organ, 2004, 82:844-851.
3. 许艳, 陈松.玻璃体腔重复注射抗血管内皮生长因子单克隆抗体bevacizumab对糖尿病大鼠视网膜的毒性观察[J].中华眼底病杂志, 2011, 27:240-244.
4. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells[J].Science, 1999, 284:143-147.
5. Mageed AS, Pietryga DW, DeHeer DH, et al. Isolation of large numbers of mesenchymal stem cells from the washings of bone marrow collection bags:characterization of fresh mesenchymal stem cells[J].Transplantation, 2007, 83:1019-1026.
6. Lu LL, Liu YJ, Yang SG, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials[J]. Haematologica, 2006, 91:1017-1026.
7. Wang HS, Hung SC, Peng ST, et al.Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord[J].Stem Cells, 2004, 22:1330-1337.
8. Weiss ML, Medicetty S, Bledsoe AR, et al.Human umbilical cord matrix stem cells:preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease[J].Stem Cells, 2006, 24:781-792.
9. Chao KF, Fu YS, Liu SH. Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes[J/OL].PLoS One, 2008, 3:E1451[2008-01-16]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2180192/.
10. Tsai PJ, Wang HS, Shyr YM, et al.Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats[J].J Biomed Sci, 2012, 19:47.
11. Liao W, Zhong J, Yu J, et al.Therapeutic benefit of human umbilical cord derived mesenchymal stromal cells in intracerebral hemorrhage rat:implications of anti-inflammation and angiogenesis[J]. Cell Physiol Biochem, 2009, 24:307-316.
12. Hill AJ, Al-Allaf F, Shah M, et al. Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model[J].Exp Neurol, 2009, 216:439-448.
13. Scalinci SZ, Scorolli L, Corradetti G, et al. Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes:neuroprotective growth factors in the vitreous[J].Clin Ophthalmol, 2011, 5:691-696.
14. Fujieda H, Sasaki H. Expression of brain-derived neurotrophic factor in cholinergic and dopaminergic amacrine cells in the rat retina and the effects of constant light rearing[J].Exp Eye Res, 2008, 86:335-343.
15. Clarke DB, Wang YC, Bray GM, et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells[J]. Proc Natl Acad Sci USA, 1994, 91:1632-1636.
16. Ankrum J, Karp JM. Mesenchymal stem cell therapy:two steps forward, one step back[J].Trends Mol Med, 2010, 16:203-209.

Chinese Journal of Ocular Fundus Diseases

Systemic and ocular transplantation of human umbilical cord mesenchymal stem cells into rats with diabetic retinopathy

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