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富集的人胚胎干细胞来源的CD133、CD24肾祖细胞在庆大霉素诱导的小鼠肾损伤中植入并恢复功能。

Enriched human embryonic stem cells-derived CD133, CD24 renal progenitors engraft and restore function in a gentamicin-induced kidney injury in mice.

作者信息

Bahrami Maryam, Abbaszadeh Hojjat Allah, Norouzian Mohsen, Abdollahifar Mohammad-Amin, Roozbahany Navid Ahmady, Saber Maryam, Azimi Masoumeh, Ehsani Ehsan, Bakhtiyari Mohsen, Serra Andreas L, Moghadasali Reza

机构信息

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Laser Applications in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Regen Ther. 2024 May 7;27:506-518. doi: 10.1016/j.reth.2024.04.015. eCollection 2024 Dec.

DOI:10.1016/j.reth.2024.04.015
PMID:38745839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11091464/
Abstract

INTRODUCTION

Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI.

METHODS

Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24 renal progenitor cells and evaluate their functional activity in alleviating AKI.

RESULTS

The obtained results show that hESCs-derived CD133+CD24 RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis.

CONCLUSION

The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.

摘要

引言

急性肾损伤（AKI）是一个常见的健康问题，会导致高发病率和潜在死亡率。传统治疗方法无法改善这种病症，这凸显了创新且有效治疗方法的必要性。利用肾祖细胞（RPCs）进行再生治疗已被提出作为一种有前景的新策略。越来越多的证据表明，从包括人类胚胎干细胞（hESCs）在内的不同来源分化而来的祖细胞能够有效治疗AKI。

方法

在此，我们描述一种生成RPCs并将人定向胚状体（EBs）诱导为CD133+CD24肾祖细胞的方法，并评估它们在减轻AKI方面的功能活性。

结果

所获结果表明，hESCs来源的CD133+CD24 RPCs能够植入庆大霉素诱导肾损伤小鼠的受损肾小管，恢复肾功能和结构，显著降低血尿素氮水平，抑制氧化应激和炎症，减轻包括肾小管坏死、肾小管扩张、管型和间质纤维化在内的组织病理学紊乱。

结论

结果表明，RPCs在改善肾病方面具有有前景的再生潜力，可为未来的细胞治疗和疾病建模奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/4258721241ec/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/bc8045f4cac9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/a813ee8f6874/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/ceecf424f3fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/be63e43525d8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/d7dd30490197/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/4efb50ee9051/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/b68a8efcfcf2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/92cfeeb1349f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/4258721241ec/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/bc8045f4cac9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/a813ee8f6874/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/ceecf424f3fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/be63e43525d8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/d7dd30490197/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/4efb50ee9051/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/b68a8efcfcf2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/92cfeeb1349f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc99/11091464/4258721241ec/figs1.jpg

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