Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques

被引：9

作者：

Lin, Yongshun ^{[1
]}

Sato, Noriko ^{[2
]}

Hong, Sogun ^{[3
]}

Nakamura, Kenta ^{[4
,5
]}

Ferrante, Elisa A. ^{[6
]}

Yu, Zu Xi ^{[7
]}

Chen, Marcus Y. ^{[8
]}

Nakamura, Daisy S. ^{[4
,5
,15
]}

Yang, Xiulan ^{[4
,9
]}

Clevenger, Randall R. ^{[10
]}

Hunt, Timothy J. ^{[10
]}

Taylor, Joni L. ^{[10
]}

Jeffries, Kenneth R. ^{[10
]}

Keeran, Karen J. ^{[10
]}

Neidig, Lauren E. ^{[4
,11
]}

Mehta, Atul ^{[6
]}

Schwartzbeck, Robin ^{[6
]}

Yu, Shiqin Judy ^{[3
]}

Kelly, Conor ^{[3
]}

Navarengom, Keron ^{[6
]}

Takeda, Kazuyo ^{[12
]}

Adler, Stephen S. ^{[13
]}

Choyke, Peter L. ^{[2
]}

Zou, Jizhong ^{[1
]}

Murry, Charles E. ^{[4
,5
,9
,14
]}

Boehm, Manfred ^{[6
]}

Dunbar, Cynthia E. ^{[3
]}

机构：

[1] NHLBI, iPSC Core, NIH, Bethesda, MD 20892 USA

[2] NCI, Lab Cellular Therapeut, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA

[3] NHLBI, Translat Stem Cell Biol Branch, NIH, Bethesda, MD 20892 USA

[4] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA

[5] Univ Washington, Dept Med Cardiol, Seattle, WA 98195 USA

[6] NHLBI, Translat Vasc Med Branch, NIH, Bethesda, MD 20892 USA

[7] NHLBI, Pathol Core, NIH, Bethesda, MD 20892 USA

[8] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA

[9] Univ Washington, Sch Med, Dept Lab Med & Pathol, Seattle, WA 98195 USA

[10] NHLBI, Anim Surg & Resources Core, NIH, Bethesda, MD 20892 USA

[11] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA

[12] US FDA, Microscopy & Imaging Core, CBER, Silver Spring, MD USA

[13] Frederick Natl Lab Canc Res, Clin Res Directorate, Frederick, MD 21701 USA

[14] Univ Washington, Sch Med, Dept Bioengn, Seattle, WA 98195 USA

[15] Astellas Pharm, Universal Cells, Seattle, WA 98121 USA

来源：

CELL STEM CELL | 2024年 / 31卷 / 07期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; INDUCED PLURIPOTENT; IN-VIVO; MYOCARDIAL-INFARCTION; DIFFERENTIATED CELLS; PARKINSONS-DISEASE; SYMPORTER NIS; TRANSPLANTATION; IMMUNOGENICITY; EXPRESSION;

D O I：

10.1016/j.stem.2024.05.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.

引用

页码：974 / 988.e5

页数：21

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