Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction-Reference-Cited by-同舟云学术

Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction

Published:2023-12 Issue:48 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Hao Tian¹^ORCID,Ji Guangbo¹^ORCID,Qian Meng¹^ORCID,Li Qiu Xuan²,Huang Haoyan³,Deng Shiyu⁴,Liu Pei¹,Deng Weiliang¹^ORCID,Wei Yongzhen¹,He Ju⁵,Wang Shusen⁶,Gao Wenqing⁷^ORCID,Li Tong⁷,Cheng Jiansong⁸^ORCID,Tian Jinwei⁹^ORCID,Pan Leiting⁴^ORCID,Gao Fei²^ORCID,Li Zongjin³^ORCID,Zhao Qiang¹^ORCID

Affiliation:

1. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China.

2. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

3. Nankai University School of Medicine, Tianjin 300071, China.

4. The Key Laboratory of Weak-Light Nonlinear Photonics of Education Ministry, School of Physics and TEDA Institute of Applied Physics, Nankai University, Tianjin 300071, China.

5. Department of Vascular Surgery, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.

6. Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China.

7. Department of Heart Center, The Third Central Hospital of Tianjin, Nankai University, Tianjin, China.

8. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, China.

9. Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Abstract

Cell therapy by autologous mesenchymal stem cells (MSCs) is a clinically acceptable strategy for treating various diseases. Unfortunately, the therapeutic efficacy is largely affected by the low quality of MSCs collected from patients. Here, we showed that the gene expression of MSCs from patients with diabetes was differentially regulated compared to that of MSCs from healthy controls. Then, MSCs were genetically engineered to catalyze an NO prodrug to release NO intracellularly. Compared to extracellular NO conversion, intracellular NO delivery effectively prolonged survival and enhanced the paracrine function of MSCs, as demonstrated by in vitro and in vivo assays. The enhanced therapeutic efficacy of engineered MSCs combined with intracellular NO delivery was further confirmed in mouse and rat models of myocardial infarction, and a clinically relevant cell administration paradigm through secondary thoracotomy has been attempted.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adi9967

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