Intracerebral transplantation of human umbilical cord-derived mesenchymal stem cells in neonatal rat model of hypoxic-ischemic brain damage: protective effect to injured brain
ZHANG De-Shuang1,2, BAI Xiao-Hong1, CHEN Da-Peng1, MU De-Zhi1, CHEN Juan1
Department of Neonatology, West China Second University Hospital, Chengdu 610041, China
Abstract：Objective To study the brain protection and the possible mechanism of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs) in neonatal rat model of hypoxic-ischemic brain damage（HIBD). Methods Successfully establishing a neonatal rat model of HIBD, hUC-MSCs labeled with BrdU were transplanted into the lateral ventricle 24 hours after HIBD. The number of apoptotic cells and the expression of Caspase-3 were detected by TUNEL and Western blot respectively at 24 and 48 hours after transplantation. The neurological functions of HIBD rats were evaluated by Longa score, and the survival, differentiation and pro-differentiation effects of hUC-MSCs were identified by immunofluorescence at 1 to 3 weeks after transplantation. Results At 24 and 48 hours after transplantation, apoptotic cells and Caspase-3 expression in the MSCs group were less than in the HIBD group（PPPPConclusion hUC-MSCs transplantation in HIBD rats can inhibit Caspase-3 expression and reduce apoptotic cells in the early stage, and in the later period, the survival hUC-MSCs can differentiate into neural-like cells and promote the differentiation of endogenous neural-like cells, providing protective effects to brain.
ZHANG De-Shuang,BAI Xiao-Hong,CHEN Da-Peng et al. Intracerebral transplantation of human umbilical cord-derived mesenchymal stem cells in neonatal rat model of hypoxic-ischemic brain damage: protective effect to injured brain[J]. CJCP, 2014, 16(9): 927-932.
Xia G, Hong X, Chen X, et al.Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood alleviates hypoxic ischemic brain injury in rat neonates[J].J Perinat Med, 2010, 38(2): 215-221.
[2]
Wei X, Du Z, Zhao L, et al.IFATS collection: The conditioned media of adipose stromal cells protect against hypoxia-ischemia-induced brain damage in neonatal rats[J].Stem Cells, 2009,27(2): 478-488.
[3]
Nakajima W, Ishida A, Lange MS, et al.Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat[J].J Neurosci, 2000, 20(21): 7994-8004.
[4]
Zhao H, Sapolsky RM, Steinberg GK.Phosphoinositide-3-kinase/akt survival signal pathways are implicated in neuronal survival after stroke[J].Mol Neurobiol, 2006, 34(3): 249-270.
[5]
Rice JE 3rd, Vannucci RC, Brierley JB.The influence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neurol, 1981, 9(2): 131-141.
[6]
Longa EZ, Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989, 20(1): 84-91.
[7]
Nakka VP, Gusain A, Mehta SL, et al.Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities[J].Mol Neurobiol, 2008, 37(1): 7-38.
[8]
Muñoz-Pinedo C.Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense[J].Adv Exp Med Biol, 2012, 738: 124-143.
[9]
Neuhoff S, Moers J, Rieks M, et al.Proliferation, differentiation and cytokin secretion of human umbilical cord blood-derived mononuclear cells in vitro[J].Exp Hematol, 2007, 35(7): 1119-1131.
[10]
Bona E, Andersson AL, Blomgren K, et al.Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats[J].Pediatr Res,1999, 45(4 Pt 1): 500-509.
[11]
Levenberg S, Burdick JA, Kraehenbuehl T, et al.Neurotrophin-induced differentiation of human embryonic stem cells on three-dimensional polymeric scaffolds[J].Tissue Eng, 2005, 11(3-4):506-512.
[12]
Pimentel-Coelho PM, Magalhães ES, Lopes LM, et al.Human cord blood transplantation in a neonatal rat model of hypoxic-ischemic brain damage: functional outcome related to neuroprotection in the striatum[J].Stem Cells Dev, 2010, 19(3):351-358.
[13]
Zheng T, Rossignol C, Leibovici A, et al.Transplantation of multipotent astrocytic stem cells into a rat model of neonatal hypoxic-ischemic encephalopathy[J].Brain Res, 2006, 1112(1):99-105.
[14]
Kitada M, Dezawa M.Induction system of neural and muscle lineage cells from bone marrow stromal cells; a new strategy for tissue reconstruction in degenerative diseases[J].Histol Histopathol, 2009, 24(5): 631-642.
[15]
Chopp M, Li Y.Treatment of neural injury with marrow stromal cells[J].Lancet Neurol, 2002, 1(2): 92-100.
[16]
Chen J, Sanberg PR, Li Y, et al.Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats[J].Stroke, 2001, 32(11): 2682 -2688.
