Gut microbiota modulation in cardiac cell therapy with immunosuppression in a nonhuman primate ischemia/reperfusion model.

IF 6.4 1区医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2025-01-15 DOI:10.1038/s41536-025-00390-6

Hung-Chih Chen, Yu-Che Cheng, Marvin L Hsieh, Po-Ju Lin, Emily F Wissel, Theodore Steward, Cindy M C Chang, Jennifer Coonen, Timothy A Hacker, Timothy J Kamp, Patrick C H Hsieh

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Abstract

Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity. Immunosuppression promoted anaerobes, such as Faecalibacterium, Streptococcus, Anaerovibrio and Dialister, and altered amino acid metabolism and nucleosides/nucleotides biosynthesis in host plasma. EC + CM cotreatment favors Phascolarctobacterium, Fusicatenibacter, Erysipelotrichaceae UCG-006, Veillonella and Mailhella. Remarkably, gut microbiota of the EC/CM co-treatment group resembled that of the pre-injury group, and the NHPs exhibited a metabolic shift towards amino acid and fatty acid/lipid biosynthesis in plasma following cell therapy. The interplay between shift in microbial community and host homeostasis during treatment suggests gut microbiome modulation could improve cell therapy outcomes.

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在非人灵长类动物缺血/再灌注模型中，免疫抑制心肌细胞治疗中的肠道微生物群调节。

肠道菌群影响移植结果；然而，免疫抑制和细胞治疗对心血管护理中肠道微生物群的影响仍未被探索。我们研究了非人灵长类动物（NHP）心脏缺血/再灌注模型在免疫抑制和接受人诱导多能干细胞（hiPSC）来源的内皮细胞（EC）和心肌细胞（CM）细胞治疗时的肠道微生物群动力学。免疫抑制和EC/CM联合治疗均增加了肠道微生物群α的多样性。免疫抑制促进了厌氧菌，如粪杆菌、链球菌、厌氧弧菌和Dialister，并改变了宿主血浆中的氨基酸代谢和核苷/核苷酸的生物合成。EC + CM共处理有利于Phascolarctobacterium， Fusicatenibacter，丹毒科UCG-006， Veillonella和Mailhella。值得注意的是，EC/CM联合治疗组的肠道微生物群与损伤前组相似，细胞治疗后血浆中NHPs的代谢向氨基酸和脂肪酸/脂质生物合成转变。在治疗过程中，微生物群落的变化和宿主体内平衡之间的相互作用表明肠道微生物组调节可以改善细胞治疗的结果。

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来源期刊

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

审稿时长

12 weeks

期刊介绍： Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.