牙髓干细胞对中枢神经系统疾病的治疗新进展
|
摘要
牙髓干细胞(dental pulp stem cells,DPSC)是神经嵴来源的外胚间充质干细胞,具有强大的自我更新和多向分化能力,可以用相对容易的方法从拔除的牙齿牙髓中分离出来。越来越多的证据表明,牙髓干细胞疗法在中枢神经系统(central nervous system,CNS)疾病和视网膜损伤疾病的治疗中有很大的潜力。牙髓干细胞可以通过多个途径产生疗效,特别是旁分泌介导分泌的一系列营养因子,被视为其发挥作用的主导机制。本文就牙髓干细胞修复中枢神经系统损伤的最新证据展开综述,包括其对视网膜神经节细胞的神经保护作用及在视神经损伤的再生与青光眼的治疗中的作用。
Dental pulp stem cells( DPSC) are mesenchymal stem cells derived from neural crest,which have strong self-renewal and multidifferentiation ability. They can be removed from the tooth pulp of the extracted tooth in a relatively easy way. Accumulating evidence suggested that dental pulp stem cell therapy has a great potential in the treatment of diseases of the central nervous system( CNS) and retinal damage. Dental pulp stem cells can produce therapeutic effects in a number of ways,especially a series of trophic factors mediated by paracrine secretion,which is seen as the dominant mechanism for its function. In this paper,the latest evidence about the repair of central nervous system injury by dental pulp stem cells,including neuroprotective effects on retinal ganglion cells and the role in optic nerve regeneration and the treatment of glaucoma,is reviewed.
Dental pulp stem cells( DPSC) are mesenchymal stem cells derived from neural crest,which have strong self-renewal and multidifferentiation ability. They can be removed from the tooth pulp of the extracted tooth in a relatively easy way. Accumulating evidence suggested that dental pulp stem cell therapy has a great potential in the treatment of diseases of the central nervous system( CNS) and retinal damage. Dental pulp stem cells can produce therapeutic effects in a number of ways,especially a series of trophic factors mediated by paracrine secretion,which is seen as the dominant mechanism for its function. In this paper,the latest evidence about the repair of central nervous system injury by dental pulp stem cells,including neuroprotective effects on retinal ganglion cells and the role in optic nerve regeneration and the treatment of glaucoma,is reviewed.
引文
[1]Berry M,Ahmed Z,Lorber B,et al.Regeneration of axons in the visual system[J].Restor Neurol Neurosci,2008,26(2/3):147-174.
[2]Gronthos S,Brahim J,Li W,et al.Stem cell properties of human dental pulp stem cells[J].J Dent Res,2002,81(8):531-535.
[3]Kawashima N.Characterisation of dental pulp stem cells:A new horizon for tissue regeneration[J].Arch Oral Biol,2012,57(11):1439-1458.
[4]Sakai K,Yamamoto A,Matsubara K,et al.Human dental pulpderived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms[J].J Clin Invest,2012,122(1):80-90.
[5]Mead B,Berry M,Logan A,et al.Stem cells for treatment of degenerative eye disease[J].Stem Cell Res,2015,14(3):243-257.
[6]Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo[J].Proc Nat Acad Sci,2000,97(25):13625-13630.
[7]Huang GTJ,Gronthos S,Shi S.Mesenchymal stem cells derived from dental tissues vs.those from other sources:Their biology and role in regenerative medicine[J].J Dent Res,2009,88(9):792-806.
[8]Davies OG,Cooper PR,Shelton RM,et al.A comparison of the in vitro mineralisation and dentinogenic potential of mesenchymal stem cells derived from adipose tissue,bone marrow and dental pulp[J].J Bone Miner Metab,2015,33(4):371-382.
[9]Ullah I,Subbarao RB,Kim EJ,et al.In vitro comparative analysis of human dental stem cells from a single donor and its neuronal differentiation potential evaluated by electrophysiology[J].Life sciences,2016,154:39-51.
[10]Cho YA,Kim DS,Song M,et al.Protein interacting with never in mitosis A-1 induces glutamatergic and GAB aergic neuronal differentiation in human dental pulp stem cells[J].J Endod,2016,42(7):1055-1061.
[11]Goorha S,Reiter LT.Culturing and neuronal differentiation of human dental pulp stem cells[J].Curr Protoc Hum Genet,2017,21(6):1-10.
[12]Chang CC,Chang KC,Tsai SJ,et al.Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media[J].J Formos Med Assoc,2014,113(12):956-965.
[13]Arthur A,Rychkov G,Shi S,et al.Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues[J].Stem Cells,2008,26(7):1787-1795..
[14]Király M,Kádár K,Horváthy DB,et al.Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo[J].Neurochem Int,2011,59(3):371-381.
[15]Mead B,Logan A,Berry M,et al.Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury dental pulp stem cells for optic nerve injury[J].Invest Ophthalmol Vis Sci,2013,54(12):7544-7556.
[16]Nosrat IV,Widenfalk J,Olson L,et al.Dental pulp cells produce neurotrophic factors,interact with trigeminal neurons in vitro,and rescue motoneurons after spinal cord injury[J].Dev Biol,2001,238(1):120-132.
[17]Mead B,Logan A,Berry M,et al.Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells:comparison with human bone marrow and adipose-derived mesenchymal stem cells[J].PLo S One,2014,9(10):e109305.
[18]Arthur A,Shi S,Zannettino ACW,et al.Implanted adult human dental pulp stem cells induce endogenous axon guidance[J].Stem Cells,2009,27(9):2229-2237.
[19]Teixeira FG,Carvalho MM,Sousa N,et al.Mesenchymal stem cells secretome:A new paradigm for central nervous system regeneration[J].Cell Mol Life Sci,2013,70(20):3871-3882.
[20]Castorina A,Szychlinska MA,Marzagalli R,et al.Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders:Is the escape from senescence an answer[J].Neural Regen Res,2015,10(6):850-858.
[21]Mead B,Scheven BA.Mesenchymal stem cell therapy for neuroprotection and axon regeneration[J].Neural Regen Res,2015,10(6):371-373.
[22]Huang AHC,Snyder BR,Cheng PH,et al.Putative dental pulpderived stem/stromal cells promote proliferation and differentiation of endogenous neural cells in the hippocampus of mice[J].Stem Cells,2008,26(10):2654-2663.
[23]Leong WK,Henshall TL,Arthur A,et al.Human adult dental pulp stem cells enhance poststroke functional recovery through nonneural replacement mechanisms[J].Stem Cells Transl Med,2012,1(3):177-187.
[24]Fang C,Yang Y,Wang Q,et al.Intraventricular injection of human dental pulp stem cells improves hypoxic-ischemic brain damage in neonatal rats[J].PLo S one,2013,8(6):e66748.
[25]Yamagata M,Yamamoto A,Kako E,et al.Human dental pulpderived stem cells protect against hypoxic-ischemic brain injury in neonatal mice[J].Stroke,2013,44(2):551-554.
[26]Liu R,Liu YC,Meng J,et al.A microfluidics-based mobility shift assay to identify new inhibitors ofβ-secretase for Alzheimer’s disease[J].Anal Bioanal Chem,2017,409(28):6635-6642.
[27]Apel C,Forlenza OV,De Paula VJR,et al.The neuroprotective effect of dental pulp cells in models of Alzheimer’s and Parkinson’s disease[J].J Neural Transm,2009,116(1):71-78.
[28]Ahmed NEMB,Murakami M,Hirose Y,et al.Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment:An in vitro study[J].Stem Cells Int,2016,2016:8102478.
[29]Martens W,Sanen K,Georgiou M,et al.Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro[J].FASEB J,2014,28(4):1634-1643.
[30]Taghipour Z,Karbalaie K,Kiani A,et al.Transplantation of undifferentiated and induced human exfoliated deciduous teethderived stem cells promote functional recovery of rat spinal cord contusion injury model[J].Stem Cells Dev,2011,21(10):1794-1802.
[31]Lamba DA,Mc Usic A,Hirata RK,et al.Generation,purification and transplantation of photoreceptors derived from human induced pluripotent stem cells[J].PLo S One,2010,5(1):e8763.
[32]Mac Laren RE,Pearson RA,Mac Neil A,et al.Retinal repair by transplantation of photoreceptor precursors[J].Nature,2006,444(7116):203-207.
[33]Bray AF,Cevallos RR,Gazarian K,et al.Human dental pulp stem cells respond to cues from the rat retina and differentiate to express the retinal neuronal marker rhodopsin[J].Neurosci,2014,280:142-155.
[34]Roozafzoon R,Lashay A,Vasei M,et al.Dental pulp stem cells differentiation into retinal ganglion-like cells in a three dimensional network[J].Biochem Biophys Res Commun,2015,457(2):154-160.
[35]ohnson TV,Bull ND,Hunt DP,et al.Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma[J].Inves Ophthalmol Vis Sci,2010,51(4):2051-2059.
[36]Tan HB,Kang X,Lu SH,et al.The therapeutic effects of bone marrow mesenchymal stem cells after optic nerve damage in the adult rat[J].Clin Interven Aging,2015,10:487-490.
[2]Gronthos S,Brahim J,Li W,et al.Stem cell properties of human dental pulp stem cells[J].J Dent Res,2002,81(8):531-535.
[3]Kawashima N.Characterisation of dental pulp stem cells:A new horizon for tissue regeneration[J].Arch Oral Biol,2012,57(11):1439-1458.
[4]Sakai K,Yamamoto A,Matsubara K,et al.Human dental pulpderived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms[J].J Clin Invest,2012,122(1):80-90.
[5]Mead B,Berry M,Logan A,et al.Stem cells for treatment of degenerative eye disease[J].Stem Cell Res,2015,14(3):243-257.
[6]Gronthos S,Mankani M,Brahim J,et al.Postnatal human dental pulp stem cells(DPSCs)in vitro and in vivo[J].Proc Nat Acad Sci,2000,97(25):13625-13630.
[7]Huang GTJ,Gronthos S,Shi S.Mesenchymal stem cells derived from dental tissues vs.those from other sources:Their biology and role in regenerative medicine[J].J Dent Res,2009,88(9):792-806.
[8]Davies OG,Cooper PR,Shelton RM,et al.A comparison of the in vitro mineralisation and dentinogenic potential of mesenchymal stem cells derived from adipose tissue,bone marrow and dental pulp[J].J Bone Miner Metab,2015,33(4):371-382.
[9]Ullah I,Subbarao RB,Kim EJ,et al.In vitro comparative analysis of human dental stem cells from a single donor and its neuronal differentiation potential evaluated by electrophysiology[J].Life sciences,2016,154:39-51.
[10]Cho YA,Kim DS,Song M,et al.Protein interacting with never in mitosis A-1 induces glutamatergic and GAB aergic neuronal differentiation in human dental pulp stem cells[J].J Endod,2016,42(7):1055-1061.
[11]Goorha S,Reiter LT.Culturing and neuronal differentiation of human dental pulp stem cells[J].Curr Protoc Hum Genet,2017,21(6):1-10.
[12]Chang CC,Chang KC,Tsai SJ,et al.Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media[J].J Formos Med Assoc,2014,113(12):956-965.
[13]Arthur A,Rychkov G,Shi S,et al.Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues[J].Stem Cells,2008,26(7):1787-1795..
[14]Király M,Kádár K,Horváthy DB,et al.Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo[J].Neurochem Int,2011,59(3):371-381.
[15]Mead B,Logan A,Berry M,et al.Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury dental pulp stem cells for optic nerve injury[J].Invest Ophthalmol Vis Sci,2013,54(12):7544-7556.
[16]Nosrat IV,Widenfalk J,Olson L,et al.Dental pulp cells produce neurotrophic factors,interact with trigeminal neurons in vitro,and rescue motoneurons after spinal cord injury[J].Dev Biol,2001,238(1):120-132.
[17]Mead B,Logan A,Berry M,et al.Paracrine-mediated neuroprotection and neuritogenesis of axotomised retinal ganglion cells by human dental pulp stem cells:comparison with human bone marrow and adipose-derived mesenchymal stem cells[J].PLo S One,2014,9(10):e109305.
[18]Arthur A,Shi S,Zannettino ACW,et al.Implanted adult human dental pulp stem cells induce endogenous axon guidance[J].Stem Cells,2009,27(9):2229-2237.
[19]Teixeira FG,Carvalho MM,Sousa N,et al.Mesenchymal stem cells secretome:A new paradigm for central nervous system regeneration[J].Cell Mol Life Sci,2013,70(20):3871-3882.
[20]Castorina A,Szychlinska MA,Marzagalli R,et al.Mesenchymal stem cells-based therapy as a potential treatment in neurodegenerative disorders:Is the escape from senescence an answer[J].Neural Regen Res,2015,10(6):850-858.
[21]Mead B,Scheven BA.Mesenchymal stem cell therapy for neuroprotection and axon regeneration[J].Neural Regen Res,2015,10(6):371-373.
[22]Huang AHC,Snyder BR,Cheng PH,et al.Putative dental pulpderived stem/stromal cells promote proliferation and differentiation of endogenous neural cells in the hippocampus of mice[J].Stem Cells,2008,26(10):2654-2663.
[23]Leong WK,Henshall TL,Arthur A,et al.Human adult dental pulp stem cells enhance poststroke functional recovery through nonneural replacement mechanisms[J].Stem Cells Transl Med,2012,1(3):177-187.
[24]Fang C,Yang Y,Wang Q,et al.Intraventricular injection of human dental pulp stem cells improves hypoxic-ischemic brain damage in neonatal rats[J].PLo S one,2013,8(6):e66748.
[25]Yamagata M,Yamamoto A,Kako E,et al.Human dental pulpderived stem cells protect against hypoxic-ischemic brain injury in neonatal mice[J].Stroke,2013,44(2):551-554.
[26]Liu R,Liu YC,Meng J,et al.A microfluidics-based mobility shift assay to identify new inhibitors ofβ-secretase for Alzheimer’s disease[J].Anal Bioanal Chem,2017,409(28):6635-6642.
[27]Apel C,Forlenza OV,De Paula VJR,et al.The neuroprotective effect of dental pulp cells in models of Alzheimer’s and Parkinson’s disease[J].J Neural Transm,2009,116(1):71-78.
[28]Ahmed NEMB,Murakami M,Hirose Y,et al.Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment:An in vitro study[J].Stem Cells Int,2016,2016:8102478.
[29]Martens W,Sanen K,Georgiou M,et al.Human dental pulp stem cells can differentiate into Schwann cells and promote and guide neurite outgrowth in an aligned tissue-engineered collagen construct in vitro[J].FASEB J,2014,28(4):1634-1643.
[30]Taghipour Z,Karbalaie K,Kiani A,et al.Transplantation of undifferentiated and induced human exfoliated deciduous teethderived stem cells promote functional recovery of rat spinal cord contusion injury model[J].Stem Cells Dev,2011,21(10):1794-1802.
[31]Lamba DA,Mc Usic A,Hirata RK,et al.Generation,purification and transplantation of photoreceptors derived from human induced pluripotent stem cells[J].PLo S One,2010,5(1):e8763.
[32]Mac Laren RE,Pearson RA,Mac Neil A,et al.Retinal repair by transplantation of photoreceptor precursors[J].Nature,2006,444(7116):203-207.
[33]Bray AF,Cevallos RR,Gazarian K,et al.Human dental pulp stem cells respond to cues from the rat retina and differentiate to express the retinal neuronal marker rhodopsin[J].Neurosci,2014,280:142-155.
[34]Roozafzoon R,Lashay A,Vasei M,et al.Dental pulp stem cells differentiation into retinal ganglion-like cells in a three dimensional network[J].Biochem Biophys Res Commun,2015,457(2):154-160.
[35]ohnson TV,Bull ND,Hunt DP,et al.Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma[J].Inves Ophthalmol Vis Sci,2010,51(4):2051-2059.
[36]Tan HB,Kang X,Lu SH,et al.The therapeutic effects of bone marrow mesenchymal stem cells after optic nerve damage in the adult rat[J].Clin Interven Aging,2015,10:487-490.