综述
ENGLISH ABSTRACT
提高移植光感受器功能性整合的策略
王俊
陈亦棋 [综述]
沈丽君 [综述]
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20200512-00342
Strategies to improve functional integration of transplanted photoreceptors
Wang Jun
Chen Yiqi
Shen Lijun
Authors Info & Affiliations
Wang Jun
Department of Ophthalmology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Chen Yiqi
Department of Ophthalmology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
Shen Lijun
Department of Ophthalmology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
·
DOI: 10.3760/cma.j.cn115989-20200512-00342
258
60
0
0
0
0
PDF下载
APP内阅读
摘要

视网膜退行性疾病的最终结局是光感受器的大量丢失,造成视力不可逆的损害,目前基本上无有效治疗措施。光感受器移植为一种潜在的细胞治疗手段,旨在通过替换丢失的光感受器,重建视网膜回路,在一定程度上帮助恢复视网膜功能。然而,物质交换机制的发现揭示了既往研究结果中移植光感受器的整合比例低、外段形成不足及突触形成不够等问题,显示了该疗法临床转化的难度。本文通过多个维度综述了提高移植光感受器功能性整合的策略,探究相关内容的可行性,具体包括选择最佳发育时间窗的移植细胞群,增强与宿主视网膜间的相互作用;破坏宿主外界膜,减轻视网膜重塑,提高移植细胞的迁移及整合;利用免疫调节,减少小胶质细胞活化,改善宿主的移植微环境;通过视网膜片或生物支架的移植形式,提高移植光感受器的组织性;合理地开发及使用生物材料,优化移植细胞的生理微环境;充分评估手术参数,降低手术本身对移植细胞及宿主视网膜的影响。

视网膜退行性疾病;干细胞移植;细胞治疗;光感受器;再生医学
ABSTRACT

The final outcome of the retinal degenerative diseases is the massive loss of photoreceptors, resulting in irreversible visual impairment which lacks effective treatment at present.As a potential therapeutic approach, photoreceptor transplantation can be used to restore retinal function to a certain extent by replacing the lost photoreceptors and rebuilding the retinal circuits.However, the discovery of material exchange unveiled a number of problems in previous studies, including low cellular integration, insufficient outer segment and synapse formation, highlighting the challenges of clinical translation.To explore the possibility of increasing the functional integration of photoreceptors, this article reviewed a variety of strategies, including selection of the transplanted cells with optimal developmental stage to enhance the interaction with the host retina, disruption of the outer limiting membrane and alleviation of retinal remodeling to improve the migration and integration of the transplanted photoreceptors, regulation of immunity can be used to reduce microglial activation to create a better host microenvironment for transplantation, use of retinal sheets or biological scaffolds to improve photoreceptor organization, rational development and use of biomaterials to optimize the physiological microenvironment of the transplanted cells, adequate evaluation of surgical parameters to reduce the effect of surgery on the transplanted cells and the host retina.

Retinal degeneration;Stem cell transplantation;Cell therapy;Photoreceptor;Regenerative medicine
Shen Lijun, Email: nc.defcaab.eye.liamjls
引用本文

王俊,陈亦棋,沈丽君. 提高移植光感受器功能性整合的策略[J]. 中华实验眼科杂志,2024,42(01):86-91.

DOI:10.3760/cma.j.cn115989-20200512-00342

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价
视网膜退行性疾病,如年龄相关性黄斑变性(age-related macular degeneration,AMD)和以视网膜色素变性为代表的遗传性视网膜疾病等,通常是由光感受器功能的障碍和丧失导致的 [ 1 ]。尽管不同疾病之间光感受器受损的机制不同,但最终结局是相同的,即大量光感受器丢失,造成视力不可逆的损害 [ 2 ]。目前,除了湿性AMD可以利用抗血管内皮生长因子得到一定治疗外,大多数视网膜退行性疾病还无法得到有效的控制。
光感受器移植是一种颇有前景的再生策略,旨在替换已丢失的光感受器,并重新与内层视网膜剩余神经元建立连接 [ 3 ],在一定程度上恢复视网膜的光敏性。这一策略要求视网膜下间隙的移植细胞迁移入宿主外核层,与宿主双极细胞形成突触,同时发育出对光敏感的外段与宿主视网膜色素上皮(retinal pigment epithelium,RPE)层紧密接触,通过不断的膜盘脱落和更新,以及视色素再生来维持光感受器的结构和功能 [ 4 , 5 ]
在2016年的3项研究中,研究人员通过分别标记细胞质和细胞核的实验方法发现,在光感受器移植后,主要发生物质交换——即移植细胞将细胞质所含蛋白质/RNA等转移至宿主残余的光感受器内,实现对宿主细胞的治疗作用,而发生细胞整合的比例相对较低 [ 6 , 7 , 8 ]。这种物质交换的主要特点包括:宿主和移植细胞间的物质交换双向进行;以一种短暂但频繁的方式进行,不需要持续的相互作用;与细胞外蛋白、核酸的摄取以及细胞的融合无关;似乎仅限于光感受器间 [ 6 , 7 , 8 ]。虽然物质交换的发生机制尚不明确,但其功能发挥的前提是视网膜内有足够的剩余光感受器,因此这一机制更适合用于早期退行性疾病,在晚期显然需要细胞整合才可发挥作用。
2018年,Waldron等 [ 9 ]将视锥前体细胞分别移植入视网膜结构紊乱且外界膜结构受到破坏的 Nrl -/-小鼠和引入保护基因后结构紊乱较小的 Nrl -/- RPE65 R91W/R91W 小鼠,结果显示结构紊乱的视网膜整合事件发生的比例达到23%,而结构完整的视网膜中该比例仅为6%。这证明了宿主环境影响2种机制的相对贡献,提示整合事件发生的比例可通过调控来提高 [ 9 ]
而除了整合事件比例不足外,移植光感受器还存在其他问题,包括细胞在移植后表现出取向(即光感受器外段朝向RPE层,突触端朝向外核层)能力不完全,外段发育不成熟以及突触形成不足等。为了提高光感受器的功能性整合,可选择合适的移植细胞群、对宿主环境进行一定程度的干预、改变细胞移植的形式以及优化视网膜下注射等方式。下面分别从这些方面进行介绍。
试读结束,您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Gasparini SJ Llonch S Borsch O et al. Transplantation of photoreceptors into the degenerative retina:current state and futureperspectives[J]Prog Retin Eye Res 201969137. DOI: 10.1016/j.preteyeres.2018.11.001 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Singh MS Park SS Albini TA et al. Retinal stem cell transplantation:balancing safety and potential[J/OL]Prog Retin Eye Res 202075100779[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/31494256. DOI: 10.1016/j.preteyeres.2019.100779 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Léveillard T Klipfel L Mechanisms underlying the visual benefit of cell transplantation for the treatment of retinal degenerations[J/OL]Int J Mol Sci 201920(3)∶557[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/30696106. DOI: 10.3390/ijms20030557 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Garita-Hernandez M Lampič M Chaffiol A et al. Restoration of visual function by transplantation of optogenetically engineered photoreceptors[J/OL]Nat Commun 201910(1)∶4524[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/31586094. DOI: 10.1038/s41467-019-12330-2 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Gagliardi G <x>Ben M</x> <x>'</x> <x>Barek</x> K Goureau O Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa:a pluripotent stem cell-based approach[J]Prog Retin Eye Res 201971125. DOI: 10.1016/j.preteyeres.2019.03.001 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Pearson RA Gonzalez-Cordero A West EL et al. Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors[J/OL]Nat Commun 2016713029[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/27701378. DOI: 10.1038/ncomms13029 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Singh MS Balmer J Barnard AR et al. Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion[J/OL]Nat Commun 2016713537[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/27901042. DOI: 10.1038/ncomms13537 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Santos-Ferreira T Llonch S Borsch O et al. Retinal transplantation of photoreceptors results in donor-host cytoplasmic exchange[J/OL]Nat Commun 2016713028[2022-12-16]http://www.ncbi.nlm.nih.gov/pubmed/27701381. DOI: 10.1038/ncomms13028 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Waldron PV Di Marco F Kruczek K et al. Transplanted donor- or stem cell-derived cone photoreceptors can both integrate and undergo material transfer in an environment-dependent manner[J]Stem Cell Reports 201810(2)∶406421. DOI: 10.1016/j.stemcr.2017.12.008 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Bartsch U Oriyakhel W Kenna PF et al. Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice[J]Exp Eye Res 200886(4)∶691700. DOI: 10.1016/j.exer.2008.01.018 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Pearson RA Barber AC Rizzi M et al. Restoration of vision after transplantation of photoreceptors[J]Nature 2012485(7396)∶99103. DOI: 10.1038/nature10997 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Decembrini S Martin C Sennlaub F et al. Cone genesis tracing by the Chrnb4-EGFP mouse line:evidences of cellular material fusion after cone precursor transplantation[J]Mol Ther 201725(3)∶634653. DOI: 10.1016/j.ymthe.2016.12.015 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Quinn P Wijnholds J Retinogenesis of the human fetal retina:an apical polarity perspective[J/OL]Genes (Basel) 201910(12)∶987[2022-12-18]http://www.ncbi.nlm.nih.gov/pubmed/31795518. DOI: 10.3390/genes10120987 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Sridhar A Hoshino A Finkbeiner CR et al. Single-cell transcriptomic comparison of human fetal retina,hPSC-derived retinal organoids,and long-term retinal cultures[J]Cell Rep 202030(5)∶16441659. DOI: 10.1016/j.celrep.2020.01.007 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Welby E Lakowski J Di Foggia V et al. Isolation and comparative transcriptome analysis of human fetal and iPSC-derived cone photoreceptor cells[J]Stem Cell Reports 20179(6)∶18981915. DOI: 10.1016/j.stemcr.2017.10.018 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Zhu J Cifuentes H Reynolds J et al. Immunosuppression via loss of IL2rγ enhances long-term functional integration of hESC-derived photoreceptors in the mouse retina[J]Cell Stem Cell 201720(3)∶374384. DOI: 10.1016/j.stem.2016.11.019 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Collin J Zerti D Queen R et al. CRX expression in pluripotent stem cell-derived photoreceptors marks a transplantable subpopulation of early cones[J]Stem Cells 201937(5)∶609622. DOI: 10.1002/stem.2974 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Zhu J Reynolds J Garcia T et al. Generation of transplantable retinal photoreceptors from a current good manufacturing practice-manufactured human induced pluripotent stem cell line[J]Stem Cells Transl Med 20187(2)∶210219. DOI: 10.1002/sctm.17-0205 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Gasparini SJ Tessmer K Reh M et al. Transplanted human cones incorporate into the retina and function in a murine cone degeneration model[J/OL]J Clin Invest 2022132(12)∶e154619[2022-12-18]http://www.ncbi.nlm.nih.gov/pubmed/35482419. DOI: 10.1172/JCI154619 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Gagliardi G <x>Ben M</x> <x>'</x> <x>Barek</x> K Chaffiol A et al. Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids[J]Stem Cell Reports 201811(3)∶665680. DOI: 10.1016/j.stemcr.2018.07.005 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Rempel SK Welch MJ Ludwig AL et al. Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker redistribution[J/OL]Cell Rep 202239(7)∶110827[2022-12-18]http://www.ncbi.nlm.nih.gov/pubmed/35584680. DOI: 10.1016/j.celrep.2022.110827 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Santos-Ferreira TF Borsch O Ader M Rebuilding the missing part-A review on photoreceptor transplantation[J/OL]Front Syst Neurosci 201610105[2022-12-18]http://www.ncbi.nlm.nih.gov/pubmed/28105007. DOI: 10.3389/fnsys.2016.00105 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Gonzalez-Cordero A Kruczek K Naeem A et al. Recapitulation of human retinal development from human pluripotent stem cells generates transplantable populations of cone photoreceptors[J]Stem Cell Reports 20179(3)∶820837. DOI: 10.1016/j.stemcr.2017.07.022 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Zou T Gao L Zeng Y et al. Organoid-derived C-Kit /SSEA4 human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents [J/OL]Nat Commun 201910(1)∶1205[2022-12-18]http://www.ncbi.nlm.nih.gov/pubmed/30872578. DOI: 10.1038/s41467-019-08961-0 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Mahato B Kaya KD Fan Y et al. Pharmacologic fibroblast reprogramming into photoreceptors restores vision[J]Nature 2020581(7806)∶8388. DOI: 10.1038/s41586-020-2201-4 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Barber AC Hippert C Duran Y et al. Repair of the degenerate retina by photoreceptor transplantation[J]Proc Natl Acad Sci U S A 2013110(1)∶354359. DOI: 10.1073/pnas.1212677110 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Ballios BG Cooke MJ Donaldson L et al. A hyaluronan-based injectable hydrogel improves the survival and integration of stem cell progeny following transplantation[J]Stem Cell Reports 20154(6)∶10311045. DOI: 10.1016/j.stemcr.2015.04.008 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Zarbin M Cell-based therapy for retinal disease:the new frontier[J]Methods Mol Biol 20 19 1834367381. DOI: 10.1007/978-1-4939-8669-9_23 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Pearson RA Barber AC West EL et al. Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina[J]Cell Transplant 201019(4)∶487503. DOI: 10.3727/096368909X486057 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Ripolles-Garcia A Dolgova N Phillips MJ et al. Systemic immunosuppression promotes survival and integration of subretinally implanted human ESC-derived photoreceptor precursors in dogs[J]Stem Cell Reports 202217(8)∶18241841. DOI: 10.1016/j.stemcr.2022.06.009 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Pfeiffer RL Marc RE Jones BW . Persistent remodeling and neurodegeneration in late-stage retinal degeneration[J/OL]Prog Retin Eye Res 202074100771[2022-12-20]http://www.ncbi.nlm.nih.gov/pubmed/31356876. DOI: 10.1016/j.preteyeres.2019.07.004 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Hippert C Graca AB Barber AC et al. Müller glia activation in response to inherited retinal degeneration is highly varied and disease-specific[J/OL]PLoS One 201510(3)∶e0120415[2022-12-20] http://www.ncbi.nlm.ni h.gov/pubmed/25793273 . DOI: 10.1371/journal.pone.0120415 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Ma J Kabiel M Tucker BA et al. Combining chondroitinase ABC and growth factors promotes the integration of murine retinal progenitor cells transplanted into Rho -/- mice [J]Mol Vis 20111717591770.
返回引文位置Google Scholar
百度学术
万方数据
[34]
Yao J Tucker BA Zhang X et al. Robust cell integration from co-transplantation of biodegradable MMP2-PLGA microspheres with retinal progenitor cells[J]Biomaterials 201132(4)∶10411050. DOI: 10.1016/j.biomaterials.2010.09.063 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Kramer J Chirco KR Lamba DA . Immunological considerations for retinal stem cell therapy[J]Adv Exp Med Biol 2019118699119. DOI: 10.1007/978-3-030-28471-8_4 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Neves J Zhu J Sousa-Victor P et al. Immune modulation by MANF promotes tissue repair and regenerative success in the retina[J/OL]Science 2016353(6294)∶aaf3646[2022-12-22]http://www.ncbi.nlm.nih.gov/pubmed/27365452. DOI: 10.1126/science.aaf3646 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Rashid K Akhtar-Schaefer I Langmann T Microglia in retinal degeneration[J/OL]Front Immunol 2019101975[2022-12-22]http://www.ncbi.nlm.nih.gov/pubmed/31481963. DOI: 10.3389/fimmu.2019.01975 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Di Pierdomenico J Scholz R Valiente-Soriano FJ et al. Neuroprotective effects of FGF2 and minocycline in two animal models of inherited retinal degeneration[J]Invest Ophthalmol Vis Sci 201859(11)∶43924403. DOI: 10.1167/iovs.18-24621 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Di Pierdomenico J García-Ayuso D Agudo-Barriuso M et al. Role of microglial cells in photoreceptor degeneration[J]Neural Regen Res 201914(7)∶11861190. DOI: 10.4103/1673-5374.251204 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
<x>O</x> <x>'</x> <x>Koren</x> EG Yu C Klingeborn M et al. Microglial function is distinct in different anatomical locations during retinal homeostasis and degeneration[J]Immunity 201950(3)∶723737. DOI: 10.1016/j.immuni.2019.02.007 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Mandai M Fujii M Hashiguchi T et al. iPSC-derived retina transplants improve vision in rd1 end-stage retinal-degeneration mice[J]Stem Cell Reports 20178(1)∶6983. DOI: 10.1016/j.stemcr.2016.12.008 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Iraha S Tu HY Yamasaki S et al. Establishment of immunodeficient retinal degeneration model mice and functional maturation of human ESC-derived retinal sheets after transplantation[J]Stem Cell Reports 201810(3)∶10591074. DOI: 10.1016/j.stemcr.2018.01.032 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Tu HY Watanabe T Shirai H et al. Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration[J]EBioMedicine 201939562574. DOI: 10.1016/j.ebiom.2018.11.028 .
返回引文位置Google Scholar
百度学术
万方数据
[44]
McLelland BT Lin B Mathur A et al. Transplanted hESC-derived retina organoid sheets differentiate,integrate,and improve visual function in retinal degenerate rats[J]Invest Ophthalmol Vis Sci 201859(6)∶25862603. DOI: 10.1167/iovs.17-23646 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Lorach H Kang S Bhuckory MB et al. Transplantation of mature photoreceptors in rodents with retinal degeneration[J/OL]Transl Vis Sci Technol 20198(3)∶30[2022-12-22]http://www.ncbi.nlm.nih.gov/pubmed/31171997. DOI: 10.1167/tvst.8.3.30 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Yanai A Laver CR Gregory-Evans CY et al. Enhanced functional integration of human photoreceptor precursors into human and rodent retina in an ex vivo retinal explant model system[J]Tissue Eng Part A 201521(11-12)∶17631771. DOI: 10.1089/ten.TEA.2014.0669 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
Jung YH Phillips MJ Lee J et al. 3D microstructured scaffolds to support photoreceptor polarization and maturation[J/OL]Adv Mater 201830(39)∶e1803550[2022-12-26]http://www.ncbi.nlm.nih.gov/pubmed/30109736. DOI: 10.1002/adma.201803550 .
返回引文位置Google Scholar
百度学术
万方数据
[48]
Lee IK Xie R Luz-Madrigal A et al. Micromolded honeycomb scaffold design to support the generation of a bilayered RPE and photoreceptor cell construct[J]Bioact Mater 202330142153. DOI: 10.1016/j.bioactmat.2023.07.019 .
返回引文位置Google Scholar
百度学术
万方数据
[49]
Shrestha A Allen BN Wiley LA et al. Development of high-resolution three-dimensional-printed extracellular matrix scaffolds and their compatibility with pluripotent stem cells and early retinal cells[J]J Ocul Pharmacol Ther 202036(1)∶4255. DOI: 10.1089/jop.2018.0146 .
返回引文位置Google Scholar
百度学术
万方数据
[50]
Thompson JR Worthington KS Green BJ et al. Two-photon polymerized poly (caprolactone) retinal cell delivery scaffolds and their systemic and retinal biocompatibility[J]Acta Biomater 201994204218. DOI: 10.1016/j.actbio.2019.04.057 .
返回引文位置Google Scholar
百度学术
万方数据
[51]
Singh D Wang SB Xia T et al. A biodegradable scaffold enhances differentiation of embryonic stem cells into a thick sheet of retinal cells[J]Biomaterials 2018154158168. DOI: 10.1016/j.biomaterials.2017.10.052 .
返回引文位置Google Scholar
百度学术
万方数据
[52]
Thakur A Mishra S Pena J et al. Collective adhesion and displacement of retinal progenitor cells upon extracellular matrix substrates of transplantable biomaterials[J/OL]J Tissue Eng 201892041731417751286[2022-12-28]http://www.ncbi.nlm.nih.gov/pubmed/29344334. DOI: 10.1177/2041731417751286 .
返回引文位置Google Scholar
百度学术
万方数据
[53]
Park J Baranov P Aydin A et al. In situ cross-linking hydrogel as a vehicle for retinal progenitor cell transplantation[J]Cell Transplant 201928(5)∶596606. DOI: 10.1177/0963689719825614 .
返回引文位置Google Scholar
百度学术
万方数据
[54]
Sørensen NB . Subretinal surgery:functional and histological consequences of entry into the subretinal space[J]Acta Ophthalmol 201997Suppl A1141. 23DOI: 10.1111/aos.14249 .
返回引文位置Google Scholar
百度学术
万方数据
[55]
Wilson DJ Neuringer M Stoddard J et al. Subretinal cell-based therapy:an analysis of surgical variables to increase cell survival[J]Retina 201737(11)∶21622166. DOI: 10.1097/IAE.0000000000001462 .
返回引文位置Google Scholar
百度学术
万方数据
[56]
Scruggs BA Jiao C Cranston CM et al. Optimizing donor cellular dissociation and subretinal injection parameters for stem cell-based treatments[J]Stem Cells Transl Med 20198(8)∶797809. DOI: 10.1002/sctm.18-0210 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
沈丽君,Email: nc.defcaab.eye.liamjls
B
所有作者均声明不存在利益冲突
C
国家重点研发计划项目 (2022YFC2404305)
评论 (0条)
注册
登录
时间排序
暂无评论,发表第一条评论抢沙发
MedAI助手(体验版)
文档即答
智问智答
机器翻译
回答内容由人工智能生成,我社无法保证其准确性和完整性,该生成内容不代表我们的态度或观点,仅供参考。
生成快照
文献快照

你好,我可以帮助您更好的了解本文,请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持:

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号