曾园山
干细胞移植与中枢神经损伤修复的机制研究
个性化签名
- 姓名:曾园山
- 目前身份:
- 担任导师情况:
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学术头衔:
博士生导师,
- 职称:-
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学科领域:
人体解剖学
- 研究兴趣:干细胞移植与中枢神经损伤修复的机制研究
曾园山,医学博士。1977年开始从事组织学与胚胎学专业。1980年攻读中山医学院硕士研究生,探讨神经生长因子对体外培养神经元突起生长机制的影响。1988年攻读华西医科大学博士研究生,研究吗啡对脊髓可塑性的影响。1998~1999年在美国印第安纳州大学医学院解剖学系做博士后, 探讨脑缺血后神经元凋亡的形态机制。2003年在香港学医学院解剖学系做访问学者。现研究方向是干细胞移植与中枢神经损伤修复的机制研究。现聘任为中山大学中山医学院组织胚胎学教研室教授、博士生导师、教研室主任,中山大学脊髓损伤研究所副所长,中国解剖学会常务理事,广东省解剖学会理事长,广东省细胞生物学会副理事长,广东省神经科学会副秘书长,广东省人体生物组织工程学会常务理事,四川省干细胞应用研究中心重点实验室学术委员会委员,中山大学干细胞与组织工程研究中心学术委员会委员,中国解剖学报编委、中国组织化学与细胞化学杂志编委和解剖学研究杂志副主编。获国务院特殊津贴专家荣誉。
2001年主编高等医学院校选用教材《人体结构学》。2001年主编《组织学和胚胎学---考试辅导丛书》。2001年、2004年和2008年参编人民卫生出版社全国规划教材《组织学与胚胎学 (第5、6、7版,5年制)》。2002年参编全国高等医药院校教材《医用神经生物学》。2003年参与《现代组织学》担任该书编者。2004年主编《组织学和胚胎学》专科生用教材。2005年和2009年参编人民卫生出版社全国规划教材《组织学与胚胎学 (8年制)》。2006年作为副主编参编中国科学院教材建设专家委员会规划教材《textbook of histology and embryology,组织学与胚胎学英文版》。2006年主编《组织学与胚胎学考点》。2006年作为副主编参编《医用组织学》。2007年参编人民卫生出版社全国规划教材《发育生物学》。2007年作为副主编参编《发育神经生物学》。
自1984年至现在,在国内、外学术刊物上发表论文110余篇。共获24项校内、外科研基金,其中有国家自然科学基金(5项)、广东省自然科学基金(2项)、广东省社会发展攻关基金(1项)和国家教育部科研基金(2项)等。1999年参与鞠躬院士负责的国家重点基础研究课题(973)"脊髓损伤修复的研究"。1998年,"吗啡促进脊髓可塑性变化的研究",获卫生部科技进步奖三等奖。1996年,"吗啡促进脊髓损伤修复的研究",获成都市科技进步奖三等奖。2008年,"人神经营养素-3受体基因重组腺病毒构建方法",获中华人民共和国发明专利。培养和指导博士生14名、硕士生22名和博士后1名。
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2009-08-24
曾园山, q.g. chen a, y.s. zeng a, *, z.q. qu a, j.y. tang a, y.j. qin a, p. chung b, r. wong c, u. haggc
phytomedicine 16(2009)830-838,-0001,():
-1年11月30日
the purpose of this study was to investigate the effects of rhodiola rosea extract and depression on the serotonin (5-ht) level, cell proliferation and quantity of neurons at cerebral hippocampus ofdepressive rats induced by chronic mild stress (cms). seventy male sprague-dawley rats were divided into seven groups (10 per group): normal control group, untreated depressive rat model group, negative control group, positive control group, low dosage rhodiola rosea extract (1.5g/kg) group, medium dosage rhodiola rosea extract (3g/kg) group and high dosage rhodiola rosea extract (6g/kg) group. after the depressive rats induced by cms had received rhodiola rosea extract for 3 weeks, the 5-ht levels at cerebral hippocampus were detected by high performance liquid chromatography. bromodeoxyuridine (brdu) was injected in vivo to label the proliferating cells at hippocampus, and morphometry was used to count the hippocampal neurons. the results showed that the 5-ht level of the three experimental groups had recovered to normal status. the immunohistochemistry of hippocampus brdu positive cells had returned to the normal level in the group of depressive rats with low dosage rhodiola rosea extract. in conclusion the results demonstrated that rhodiola rosea extract could improve 5-ht level in hippocampus in depressive rats, and low dosage rhodiola rosea could induce neural stem cell proliferation at hippocampus to return to normal level, repairing the injured neurons at hippocampus.
chronic mild stress, depression, rhodiola rosea extract, hippocampus, serotonin, cell proliferation
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2009-08-24
曾园山, ying ding , qing yan , jing-wen ruan , yan-qing zhang , wen-jie li , yu-jiao zhang , yan li , hongxin dong and yuan-shan zeng *,
bmc neuroscience(2009)1-13,-0001,():
-1年11月30日
bone marrow mesenchymal stem cells (mscs) are one of the potential tools fortreatment of the spinal cord injury; however, the survival and differentiation of mscs in an injuredspinal cord still need to be improved. in the present study, we investigated whether governor vesselelectro-acupuncture (ea) could efficiently promote bone marrow mesenchymal stem cells (mscs)survival and differentiation, axonal regeneration and finally, functional recovery in the transectedspinal cord.
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2009-08-24
曾园山, yi xiong a, yuan-shan zeng a, b, *, chen-guang zeng c, bao-ling du a, liu-min he c, da-ping quan c, wei zhang a, jun-mei wang a, jin-lang wu d, yan li a, jun li e, f
y. xiong et al./biomaterials 30(2009)3711-3722,-0001,():
-1年11月30日
to explore therapeutic potential of engineered neural tissue, we combined genetically modified neural stem cells (nscs) and poly(lactic acid-co-glycolic acid) (plga) polymers to generate an artificial neural network in vitro. nscs transfected with either nt-3 or its receptor trkc gene were seeded into plga scaffold. the nscs were widely distributed and viable in the scaffold after culturing for 14 days. immunoreactivity against map2 was detected in >70% of these grafted cells, suggesting a high rate of differentiation toward neurons. immunostaining of synapsin-i and psd95 revealed formation of synaptic structures, which was also observed under electron microscope. furthermore, using fm1-43 dynamic imaging, synapses in these differentiated neurons were found to be excitable and capable of releasing synaptic vesicles. taken together, our artificial plga construct permits nscs to differentiate toward neurons, establish connections and exhibit synaptic activities. these findings provide a biological basis for future application or transplantation of this artificial construct in neural repair
neural stem cell,, transplantation,, plga,, synapse,, nt-3,, trkc
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2009-08-24
曾园山, wei zhang a, yuan-shan zeng a, b, c, *, jun-mei wang a, ying ding a, yun li a, wutian wu d
w. zhang et al. /neuroscience research 64(2009)170-176,-0001,():
-1年11月30日
skin-derived precursors (skps) are derived from mesoblast and can differentiate into smooth muscle cells, adipocytes, and less neuronal phenotypes. this study demonstrates that retinoic acid (ra) improves skps exit from self-proliferation to neural differentiation through up-regulating of neurod andcell-cycle regulatory protein p21, meanwhile ra also induces p75 neurotrophin receptor (p75ntr) upregulation and apoptosis of skps. when treated sequentially with neurotrophin-3 (nt-3) after ra induction, the survival and neural differentiation of skps were enhanced significantly, and cell apoptosis induced by ra was decreased. these effects could be reversed by p75ntr inhibitor pep5 instead of trk receptor inhibitor k252a. the results indicate that nt-3 improves the neural differentiation of skps induced by ra through a p75ntr-dependent signaling pathway
skin-derived precursors,, retinoic acid,, neurotrophin-3,, neural differentiation,, p75 neurotrophin receptor
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2009-08-24
曾园山, ya-yun chen, md wei zhang, md yu-lin chen. md shui-jun chen hongxin dong, md yuan-shan zeng, md phd
acupuncture & electro-therapeutics res int. j vol.33(2008)19-31,-0001,():
-1年11月30日
this study investigated whether electro-acupuncture (ea) would improvethe survival and migration of neural stem cells (nscs) transplanted ininjured spinal cord as well as the potential mechanisms. tlo spinal cordsegments of 50 adult sprague-dawley (sd) rats were completely transected,and then nscs were immediately transplanted into the transected site of theexperimental animals, while control animals were sham operated withouttransplantation. five days post-operation, electro-acupuncture treatment ongv9 (zhiyang), gv6 (jizhong), gv2 (yaoshu) and gvi (changqiang)acupoints was applied for 14 days (ea nscs 14d) and 30 days (ea nscs30d). elisa and immunohistochemical staining were used to assess thecontent of neurotrophine-3 (nt-3) and the characteristics of transplantednscs. we found that the number of transplanted nscs the survived inea nscs14d group was significantly increased as compared to that of thenscs30d group (5825.20 819.01vs 4781.40 500.49, p<0.05).19immunostaining indicated that some transplanted nscs developed intomicrotubule association protein 2 (map2) positive cells and many of themdeveloped into glial fibrillary acidic protein (gfap) positive cells in thenscs30d group. further, the migration length of transplanted nscs towardcaudal tissue in the injured site was longer in the ea nscs30d group thanthat in nscs30d group (5.98 0.79mm vs 3.96 1.72mm; p<0.05). alsont-3 in injured spinal cord tissue was 23% increased in the ea nscs14dgroup. these results suggest that the combination of ea and nscs improvesthe survival and migration of nscs in injured spinal cord in rats.
electro-acupuncture, neural stem cells, stem cell transplant, cell migratory orientation, nerotrophine-3, spinal cord injury
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2009-08-24
曾园山, xuebao zhang , yuanshan zeng , wei zhang , junmei wang , jinlang wu , and jun li ,
journal of neurotrauma 24(2007)1863-1877,-0001,():
-1年11月30日
spinal cord transection results in severe neurological sequelae, and to date, there is no effective treatment. because of the limited capacity for axonal regeneration in the spinal cord, recovery is minimal. recently, efforts have been made to establish, by grafting neural tissue, a functional relay-station between the severed stumps of the injured cord. previously, we used co-transplantation of neural stem cells (nscs) and schwann cells (scs) to improve functional recovery of transected spinal cord. however, this effort has been partially impeded by limited neuronal differentiation of transplanted nscs. to circumvent this problem, we have pre-differentiated nscs toward neurons in vitro with the application of retinoic acid (ra) prior to cell grafting. further, we genetically modifiedscs to overexpress human neurotrophin-3 (hnt-3). when these cells were co-transplanted into the transected spinal cord of rats, injured animals had partial improvement (both functionally and structurally), including improved basso, beattie, and bresnahan (bbb) scores, increased axonal regeneration/remyelination, and reduced neuronal loss. however, this pre-differentiation of nscs in vitro only mildly improved neuronal differentiation of nscs in vivo.
adenovirus, co-transplantation, gene therapy, neural stem cells, nt-3,, regeneration, remyelination, retinoic acid, schwann cells, spinal cord injury
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2009-08-24
曾园山, jiasong guo a, d, yuanshan zeng e, yuxiang liang a, li wang a, huanxing su a and wutain wu a, b, c
regenerationandtransplantation vol.18 no.9 11 june(2007)863-868,-0001,():
-1年11月30日
cyclosporine is one of the foremost immunosuppressive agents for cell, tissue, and organ transplantation. cyclosporine is, however, associatedwith signicant side e
cyclosporine,, di
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2009-08-24
曾园山, yuan-shan zeng a, jun-hui nie a, wei zhang a, sui-jun chen a, wutian wu b
brainresearch 1130(2007)108-113,-0001,():
-1年11月30日
the present study investigated whether morphine can promote regeneration and synaptic reconstruction of the terminals of injured primary afferent fibers in lamina ii of the spinal cord in rats following sciatic nerve injury. fluoride-resistant acid phosphatase (frap)- positive terminals in lamina ii of the l4 spinal segment after sciatic nerve injury were assessed after treatment with vehicle, morphine, and naloxone plus morphine. under the electron microscope, types i and ii complex terminals of unmyelinated afferent fibers from the dorsal root, simple terminals of interneuronal axons, and terminals of descending axons at lamina ii of the l4 spinal segment were documented in the different groups after injury. frap-positive terminals in lamina ii were depleted after sciatic nerve injury in the vehicle group. treatment with morphine increased the numbers of frap-positive terminals, and this was prevented by naloxone. the present study demonstrates that morphine may promote the regeneration and synaptic reconstruction of the terminals of injured primary unmyelinated afferent fibers in lamina ii of spinal cord, by a process mediated by μ-opioid receptors.
spinal cord,, sciatic nerve injury,, morphine,, opioid receptor,, naloxone,, unmyelinated afferent fiber
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2009-08-24
曾园山, j-s guo , , y-s zeng *, h-b li , w-l huang , r-y liu , x-b li , y ding , l-z wu and d-z cai
spinal cord 45(2007)15-24,-0001,():
-1年11月30日
an animal model oftransected spinal cord injury (sci) was used to test thehypothesis that cografted neural stem cells (nscs) and nt-3-scs promote morphologic andfunctional recoveries of injured spinal cord.objective: to explore whether cotransplant ofnsc s and nt-3-scs could promote the injured spinal cord repair. setting: zhongshan medical college, sun yat-sen university, pr china. methods: female sprague-dawley (sd) rats weighing on 200-220g were used to prepare sci models. the spinal cord was transected between t9 and t10, then nscs, scs
neural stem cells, schwann cells, neurotrophin-3, transplantation, spinal cord injury, regeneration
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2009-08-24
曾园山, jun-mei wang a, , yuan-shan zeng a, b, ran-yi liu c, wen-lin huang c, yi xiong b, yan-hua wang d, shui-jun chen a, yang d. teng e
j.-m. wang et al./experimental neurology 203(2007)123-127,-0001,():
-1年11月30日
abstractwe have constructed a recombinant adenovirus expression vector carrying the human neurotrophin-3 (nt-3) receptor trkc (tyrosine proteinkinase c) gene (rad-trkc; 2478 bp) and confirmed the expression of the encoded trkc in green fluorescent protein (gfp)-murine neural stem cells (nscs) by reverse transcription polymerase chain reaction (rt-pcr),western blot analysis, andimmunocytochemistry. the activity of the expressedrad-trkc was verified in vitro by evaluating dose-related responses of nscs to nt-3, a trkc specific ligand. trkc-gfp-nscs had a significantly higher percentage of neuronal differentiation when treated with nt-3 relative to the rad-lacz control cells (55.2% vs. 29.8%; p<0.05, χ2 test).thus, our rad-trkc vector can transfect nscs and produce functional trkc receptors to promote neuronal differentiation of nscs.
trkc, recombinant adenovirus, gene expression, nt-3, neural stem cell, differentiation
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