Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids.
Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids.
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DOI：
10.1016/j.stemcr.2018.07.005
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发表时间：
2018-09-11
影响因子：
5.9
通讯作者：
Goureau O
中科院分区：
文献类型：
--
作者：
Gagliardi G;Ben M'Barek K;Chaffiol A;Slembrouck-Brec A;Conart JB;Nanteau C;Rabesandratana O;Sahel JA;Duebel J;Orieux G;Reichman S;Goureau O
光感受器退行性疾病是失明的主要原因，细胞替代是最令人鼓舞的策略之一。对于使用人诱导多能干细胞（hiPSC）的基于干细胞的治疗，获得同质的感光细胞群体是至关重要的。我们通过使用CRISPR/Cas9基因组编辑产生荧光锥杆同源框（Crx）报告基因hiPSC系，证实了细胞表面抗原CD 73仅在hiPSC衍生的光感受器中表达。我们证明了通过磁激活细胞分选（MACS）靶向CD 73是分离可移植光感受器的安全群体的有效策略。CD 73+光感受器前体可以大量分离并移植到大鼠眼中，显示出在光感受器变性模型的宿主内层视网膜附近存活和成熟的能力。这些数据表明，CD 73+光受体前体在未来安全的临床翻译方面前景广阔。通过基于CD 73的MACS分化和选择方案有效分离hiPSC衍生的光感受器容易转移到完全GMP条件下移植的CD 73+细胞在变性大鼠视网膜中的长期存活Gagliardi和同事显示了通过靶向单一表面抗原CD 73从人诱导多能干细胞中分离同质和功能性光感受器群体的可能性。移植的人类细胞能够被整合到宿主视网膜中，主要产生锥状光感受器。
Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We confirmed that the cell surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using CRISPR/Cas9 genome editing. We demonstrated that CD73 targeting by magnetic-activated cell sorting (MACS) is an effective strategy to separate a safe population of transplantable photoreceptors. CD73+ photoreceptor precursors can be isolated in large numbers and transplanted into rat eyes, showing capacity to survive and mature in close proximity to host inner retina of a model of photoreceptor degeneration. These data demonstrate that CD73+ photoreceptor precursors hold great promise for a future safe clinical translation. Efficient isolation of hiPSC-derived photoreceptors via CD73-based MACS Differentiation and selection protocols readily transferable to fully GMP conditions Long-term survival of transplanted CD73+ cells in degenerated rat retina Gagliardi and colleagues show the possibility of isolating a homogeneous and functional population of photoreceptors from human induced pluripotent stem cells by targeting of a single surface antigen, CD73. Transplanted human cells are able to be incorporated into a host retina, generating mostly cone photoreceptors.
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影响因子：
64.8
作者：
Pearson, R. A.;Barber, A. C.;Rizzi, M.;Hippert, C.;Xue, T.;West, E. L.;Duran, Y.;Smith, A. J.;Chuang, J. Z.;Azam, S. A.;Luhmann, U. F. O.;Benucci, A.;Sung, C. H.;Bainbridge, J. W.;Carandini, M.;Yau, K. -W.;Sowden, J. C.;Ali, R. R.
通讯作者：
Ali, R. R.
影响因子：
8.8
作者：
Belle, Morgane;Godefroy, David;Chedotal, Alain
通讯作者：
Chedotal, Alain
影响因子：
39.3
作者：
Menasche, Philippe;Vanneaux, Valerie;Larghero, Jerome
通讯作者：
Larghero, Jerome
DOI：
10.1002/stem.2051
发表时间：
2015-08
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Lakowski J;Gonzalez-Cordero A;West EL;Han YT;Welby E;Naeem A;Blackford SJ;Bainbridge JW;Pearson RA;Ali RR;Sowden JC
通讯作者：
Sowden JC
DOI：
10.1002/stem.2775
发表时间：
2018-05
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Lakowski J;Welby E;Budinger D;Di Marco F;Di Foggia V;Bainbridge JWB;Wallace K;Gamm DM;Ali RR;Sowden JC
通讯作者：
Sowden JC