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非人类灵长类动物模型中移植的骨髓源性CD34+干细胞介导的梗死心肌修复

Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model.

作者信息

Yoshioka Toru, Ageyama Naohide, Shibata Hiroaki, Yasu Takanori, Misawa Yoshio, Takeuchi Koichi, Matsui Keiji, Yamamoto Keiji, Terao Keiji, Shimada Kazuyuki, Ikeda Uichi, Ozawa Keiya, Hanazono Yutaka

机构信息

Center for Molecular Medicine, Department of Internal Medicine, Jichi Medical School, Minamikawachi, Tochigi 329-0498, Japan.

出版信息

Stem Cells. 2005 Mar;23(3):355-64. doi: 10.1634/stemcells.2004-0200.


DOI:10.1634/stemcells.2004-0200
PMID:15749930
Abstract

Rodent and human clinical studies have shown that transplantation of bone marrow stem cells to the ischemic myocardium results in improved cardiac function. In this study, cynomolgus monkey acute myocardial infarction was generated by ligating the left anterior descending artery, and autologous CD34(+) cells were transplanted to the peri-ischemic zone. To track the in vivo fate of transplanted cells, CD34(+) cells were genetically marked with green fluorescent protein (GFP) using a lentivirus vector before transplantation (marking efficiency, 41% on average). The group receiving cells (n = 4) demonstrated improved regional blood flow and cardiac function compared with the saline-treated group (n =4) at 2 weeks after transplant. However, very few transplanted cell-derived, GFP-positive cells were found incorporated into the vascular structure, and GFP-positive cardiomyocytes were not detected in the repaired tissue. On the other hand, cultured CD34(+) cells were found to secrete vascular endothelial growth factor (VEGF), and the in vivo regional VEGF levels showed a significant increase after the transplantation. These results suggest that the improvement is not the result of generation of transplanted cell-derived endothelial cells or cardiomyocytes; and raise the possibility that angiogenic cytokines secreted from transplanted cells potentiate angiogenic activity of endogenous cells.

摘要

啮齿动物和人类临床研究表明,将骨髓干细胞移植到缺血心肌可改善心脏功能。在本研究中,通过结扎左前降支动脉制造食蟹猴急性心肌梗死,并将自体CD34(+)细胞移植到缺血周边区域。为追踪移植细胞在体内的命运,移植前使用慢病毒载体用绿色荧光蛋白(GFP)对CD34(+)细胞进行基因标记(标记效率平均为41%)。与盐水处理组(n = 4)相比,接受细胞移植的组(n = 4)在移植后2周时区域血流和心脏功能得到改善。然而,发现极少有移植细胞来源的GFP阳性细胞整合到血管结构中,并且在修复组织中未检测到GFP阳性心肌细胞。另一方面,发现培养的CD34(+)细胞分泌血管内皮生长因子(VEGF),并且移植后体内区域VEGF水平显著升高。这些结果表明,改善并非移植细胞来源的内皮细胞或心肌细胞生成的结果;并增加了移植细胞分泌的血管生成细胞因子增强内源性细胞血管生成活性的可能性。

相似文献

[1]
Repair of infarcted myocardium mediated by transplanted bone marrow-derived CD34+ stem cells in a nonhuman primate model.

Stem Cells. 2005-3

[2]
GFP-transduced CD34+ and Lin- CD34- hematopoietic stem cells did not adopt a cardiac phenotype in a nonhuman primate model of myocardial infarct.

Exp Hematol. 2007-4

[3]
Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction.

Chin Med J (Engl). 2009-3-5

[4]
Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction.

Chin Med J (Engl). 2006-9-20

[5]
Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion.

Eur J Cardiothorac Surg. 2006-8

[6]
Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction.

Eur J Clin Invest. 2005-11

[7]
Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction.

J Biomed Sci. 2006-1

[8]
Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats.

Int J Cardiol. 2007-2-7

[9]
Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy.

J Thorac Cardiovasc Surg. 2005-9

[10]
Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival.

Cardiovasc Res. 2008-3-1

引用本文的文献

[1]
Current status and new horizons in stem cell therapy in cardiovascular regenerative medicine (CaVaReM): an update.

Eur J Med Res. 2025-9-3

[2]
Stem Cell Therapies in Canine Cardiology: Comparative Efficacy, Emerging Trends, and Clinical Integration.

Biomolecules. 2025-3-4

[3]
Preconditioning Effects of Neuromuscular Electrical Stimulation in Patients with Symptomatic Peripheral Arterial Disease.

J Atheroscler Thromb. 2025-8-1

[4]
CD34 positive cells as endothelial progenitor cells in biology and medicine.

Front Cell Dev Biol. 2023-4-17

[5]
New Opportunities in Heart Failure with Preserved Ejection Fraction: From Bench to Bedside… and Back.

Biomedicines. 2022-12-27

[6]
A Systematic Review of CD34+ Stem Cell Therapy as an Innovative and Efficient Treatment for the Management of Refractory Angina.

Cureus. 2022-12-18

[7]
An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development.

Cardiovasc Toxicol. 2022-9

[8]
What Is the Status of Regenerative Therapy in Heart Failure?

Curr Cardiol Rep. 2021-8-19

[9]
Angiogenic CD34 Stem Cell Therapy in Coronary Microvascular Repair-A Systematic Review.

Cells. 2021-5-8

[10]
Transplantation of CD34+ cells for myocardial ischemia.

World J Transplant. 2021-5-18

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