HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration

被引：125

作者：

Sugita, Sunao ^{[1
,2
,3
,4
]}

Mandai, Michiko ^{[1
,2
,3
,4
]}

Hirami, Yasuhiko ^{[1
,2
,3
]}

Takagi, Seiji ^{[1
,2
,3
,5
]}

Maeda, Tadao ^{[1
,2
,4
]}

Fujihara, Masashi ^{[1
,2
,3
]}

Matsuzaki, Mitsuhiro ^{[1
,2
,3
]}

Yamamoto, Midori ^{[1
,2
,3
]}

Iseki, Kyoko ^{[4
]}

Hayashi, Naoko ^{[4
]}

Hono, Ayumi ^{[4
]}

Fujino, Shoko ^{[4
]}

Koide, Naoshi ^{[1
,2
,3
,4
]}

Sakai, Noriko ^{[4
]}

Shibata, Yumiko ^{[4
]}

Terada, Motoki ^{[4
]}

Nishida, Mitsuhiro ^{[4
]}

Dohi, Hiromi ^{[6
]}

Nomura, Masaki ^{[6
]}

Amano, Naoki ^{[6
]}

Sakaguchi, Hirokazu ^{[7
]}

Hara, Chikako ^{[7
]}

Maruyama, Kazuichi ^{[8
]}

Daimon, Takashi ^{[9
]}

Igeta, Masataka ^{[9
]}

Oda, Toshihiko ^{[10
]}

Shirono, Utako ^{[10
]}

Tozaki, Misato ^{[10
]}

Totani, Kota ^{[11
]}

Sugiyama, Satoshi ^{[11
]}

Nishida, Kohji ^{[12
]}

Kurimoto, Yasuo ^{[1
,2
,3
]}

Takahashi, Masayo ^{[1
,2
,3
,4
]}

机构：

[1] Dept Ophthalmol, Kobe, Hyogo 6500047, Japan

[2] Kobe City Eye Hosp, Kobe, Hyogo 6500047, Japan

[3] Kobe City Med Ctr Gen Hosp, Dept Ophthalmol, Kobe, Hyogo 6500047, Japan

[4] RIKEN Ctr Biosyst Dynam Res, Lab Retinal Regenerat, Kobe, Hyogo 6500047, Japan

[5] Toho Univ, Sch Med, Dept Ophthalmol, Tokyo 1538515, Japan

[6] Kyoto Univ, Ctr iPS Cell Res & Applicat, Kyoto 6068567, Japan

[7] Osaka Univ, Grad Sch Med, Dept Adv Device Med, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Grad Sch Med, Dept Innovat Visual Sci, Suita, Osaka 5650871, Japan

[9] Hyogo Coll Med, Dept Biostat, Nishinomiya, Hyogo 6638501, Japan

[10] Kobe City Med Ctr Gen Hosp, Ctr Clin Res & Innovat, Kobe, Hyogo 6500047, Japan

[11] Tomey Corp, Nagoya, Aichi 4510051, Japan

[12] Osaka Univ, Grad Sch Med, Dept Ophthalmol, Suita, Osaka 5650871, Japan

来源：

JOURNAL OF CLINICAL MEDICINE | 2020年 / 9卷 / 07期

关键词：

HLA; immune reactions; macular degeneration; iPS cells; retina; transplantation; RETINAL-PIGMENT EPITHELIUM; AGE-RELATED MACULOPATHY; IMMUNE PRIVILEGE; PREVALENCE; INHIBITION;

D O I：

10.3390/jcm9072217

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient's blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

引用

页码：1 / 18

页数：18

共 33 条

[1]

Algvere PV, 1997, ACTA OPHTHALMOL SCAN, V75, P1

[2] Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD [J].

Algvere, PV ;

Gouras, P ;

Kopp, ED .

EUROPEAN JOURNAL OF OPHTHALMOLOGY, 1999, 9 (03) :217-230

[3] Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration [J].

da Cruz, Lyndon ;

Fynes, Kate ;

Georgiadis, Odysseas ;

Kerby, Julie ;

Luo, Yvonne H. ;

Ahmado, Ahmad ;

Vernon, Amanda ;

Daniels, Julie T. ;

Nommiste, Britta ;

Hasan, Shazeen M. ;

Gooljar, Sakina B. ;

Carr, Amanda-Jayne F. ;

Vugler, Anthony ;

Ramsden, Conor M. ;

Bictash, Magda ;

Fenster, Mike ;

Steer, Juliette ;

Harbinson, Tricia ;

Wilbrey, Anna ;

Tufail, Adnan ;

Feng, Gang ;

Whitlock, Mark ;

Robson, Anthony G. ;

Holder, Graham E. ;

Sagoo, Mandeep S. ;

Loudon, Peter T. ;

Whiting, Paul ;

Coffey, Peter J. .

NATURE BIOTECHNOLOGY, 2018, 36 (04) :1-+

[4] Drug therapy: Age-related macular degeneration. [J].

Fine, SL ;

Berger, JW ;

Maguire, MG ;

Ho, AC .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (07) :483-492

[5] GROWTH-CONTROL OF CULTURED MICROGLIA [J].

GANTER, S ;

NORTHOFF, H ;

MANNEL, D ;

GEBICKEHARTER, PJ .

JOURNAL OF NEUROSCIENCE RESEARCH, 1992, 33 (02) :218-230

[6] NK Cell Alloreactivity against KIR-Ligand-Mismatched HLA-Haploidentical Tissue Derived from HLA Haplotype-Homozygous iPSCs [J].

Ichise, Hiroshi ;

Nagano, Seiji ;

Maeda, Takuya ;

Miyazaki, Masaki ;

Miyazaki, Yuki ;

Kojima, Hiroto ;

Yawata, Nobuyo ;

Yawata, Makoto ;

Tanaka, Hidenori ;

Saji, Hiroh ;

Masuda, Kyoko ;

Kawamoto, Hiroshi .

STEM CELL REPORTS, 2017, 9 (03) :853-867

[7] IMMUNOLOGICAL CONSEQUENCES OF INTRAOCULAR IMPLANTATION OF RETINAL-PIGMENT EPITHELIAL ALLOGRAFTS [J].

JIANG, LQ ;

JORQUERA, M ;

STREILEIN, JW .

EXPERIMENTAL EYE RESEARCH, 1994, 58 (06) :719-728

[8] Characterization of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Sheets Aiming for Clinical Application [J].

Kamao, Hiroyuki ;

Mandai, Michiko ;

Okamoto, Satoshi ;

Sakai, Noriko ;

Suga, Akiko ;

Sugita, Sunao ;

Kiryu, Junichi ;

Takahashi, Masayo .

STEM CELL REPORTS, 2014, 2 (02) :205-218

[9] A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration [J].

Kashani, Amir H. ;

Lebkowski, Jane S. ;

Rahhal, Firas M. ;

Avery, Robert L. ;

Salehi-Had, Hani ;

Dang, Wei ;

Lin, Chih-Min ;

Mitra, Debbie ;

Zhu, Danhong ;

Thomas, Biju B. ;

Hikita, Sherry T. ;

Pennington, Britney O. ;

Johnson, Lincoln V. ;

Clegg, Dennis O. ;

Hinton, David R. ;

Humayun, Mark S. .

SCIENCE TRANSLATIONAL MEDICINE, 2018, 10 (435)

[10]

KLEIN R, 1992, OPHTHALMOLOGY, V99, P933

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