间充质干细胞治疗慢性肢体威胁性缺血的临床研究进展

doi:10.16352/j.issn.1001-6325.2025.11.1511

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (11): 1511-1515.doi: 10.16352/j.issn.1001-6325.2025.11.1511

间充质干细胞治疗慢性肢体威胁性缺血的临床研究进展

刘志强^1*, 谷旭放¹, 倪爱新¹, 范姗姗²

天津中医药大学第二附属医院 1.科学技术科; 2.临床药理中心,天津 300250

收稿日期:2024-10-13 修回日期:2025-03-25 出版日期:2025-11-05 发布日期:2025-10-24
通讯作者: ^*zhiqiangtcm@163.com
基金资助:
天津市教委科研计划(2021KJ154)

Clinical research progress on mesenchymal stem cells in the treatment of chronic limb-threatening ischemia

LIU Zhiqiang^1*, GU Xufang¹, NI Aixin¹, FAN Shanshan²

1. Department of Science and Technology; 2. Clinical Pharmacology Center, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China

Received:2024-10-13 Revised:2025-03-25 Online:2025-11-05 Published:2025-10-24
Contact: ^*zhiqiangtcm@163.com

摘要/Abstract

摘要： 慢性肢体威胁性缺血(CLTI)是一种严重的外周动脉疾病(PAD),其主要特征是肢体血流减少,导致组织损伤和功能障碍。间充质干细胞(MSCs)因其独特的再生能力和免疫调节特性,近年来已成为CLTI治疗领域的研究热点。在缺氧和组织损伤环境下,MSCs可通过分泌细胞因子、细胞分化以及细胞间信号传递等多种机制,促进血管新生、减轻炎性反应并促进组织修复,从而改善CLTI患者的症状和预后,展现出广阔的临床应用前景。

关键词: 间充质干细胞, 慢性肢体威胁性缺血, 细胞治疗, 血管新生, 临床研究

Abstract: Chronic limb-threatening ischemia (CLTI) is a serious peripheral arterial disease(PAD) characterized by reduced blood flow in the limbs, resulting in tissue damage and dysfunction. Mesenchymal stem cells (MSCs) have become a research hotspot in the field of CLTI treatment in recent years due to their unique regenerative ability and immunomodulatory properties. In the environment of hypoxia and tissue injury, MSCs can promote angiogenesis, reduce inflammation and promote tissue repair by secreting cytokines, cell differentiation and intercellular signal transduction, so as to improve the symptoms and prognosis of patients with CLTI, showing a broad clinical application prospect.

Key words: mesenchymal stem cells, chronic limb-threatening ischemia, cell therapy, angiogenesis, clinical research

中图分类号:

R543.5

刘志强, 谷旭放, 倪爱新, 范姗姗. 间充质干细胞治疗慢性肢体威胁性缺血的临床研究进展[J]. 基础医学与临床, 2025, 45(11): 1511-1515.

LIU Zhiqiang, GU Xufang, NI Aixin, FAN Shanshan. Clinical research progress on mesenchymal stem cells in the treatment of chronic limb-threatening ischemia[J]. Basic & Clinical Medicine, 2025, 45(11): 1511-1515.

参考文献

[1] 王海妍,方晓梅,刘焕萍,等. 慢性肢体威胁性缺血患者生活质量现状与影响因素分析[J]. 中国血管外科杂志(电子版),2024,16: 152-156.
[2] Sojakova D,Husakova J,Fejfarova V,et al. The use of autologous cell therapy in diabetic patients with chronic limb-threatening ischemia[J]. Int J Mol Sci,2024,25:10184. 10.3390/ijms251810184.
[3] Sajjad U,Ahmed M,Iqbal MZ,et al. Exploring mesenchymal stem cells homing mechanisms and improvement strategies[J]. Stem Cells Transl Med,2024,13:1161-1177.
[4] 王巧玲,张晓彤,徐衍,等. 3种不同来源CD146阳性间充质干细胞亚群的生物学特性比较[J]. 基础医学与临床,2020,40: 41-47.
[5] 肖凤君,黄晓东,王少霞,等. Ad-HGF基因修饰的胎盘间充质干细胞治疗兔肢体缺血的实验研究[J]. 军事医学,2016,40: 285-288.
[6] 张婉,高斌,符伟国,等. FOS样抗原1修饰间充质干细胞移植促进缺血肢体血管新生的实验研究[J]. 老年医学与保健,2022,28: 1353-1358.
[7] Peng X,Liu J,Ren L,et al. Extracellular vesicles derived from hypoxia-preconditioned bone marrow mesenchymal stem cells ameliorate lower limb ischemia by delivering miR-34c[J]. Mol Cell Biochem,2023,478:1645-1658.
[8] Huang W,Kraynak CA,Bender EC,et al. Soluble components from mesenchymal stromal cell processing exert anti-inflammatory effects and facilitate ischemic muscle regeneration[J]. Cytotherapy,2023,25:375-386.
[9] Quiroz HJ,Valencia SF,Shao H,et al. E-selectin-overexpressing mesenchymal stem cell therapy confers improved reperfusion,repair,and regeneration in a murine critical limb ischemia model[J]. Front Cardiovasc Med,2022,8:826687.doi:10.3389/fcvm.2021.826687.
[10] Heo JS,Kim S. Human adipose mesenchymal stem cells modulate inflammation and angiogenesis through exosomes[J]. Sci Rep,2022,12:2776.doi:10.1038/s41598-022-06824-1.
[11] 王晓旭,李超然,王惠,等. 脐带来源间充质干细胞抑制巨噬细胞M1极化[J]. 中国免疫学杂志,2024,40: 673-679.
[12] Court AC,Le-Gatt A,Luz-Crawford P,et al. Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response[J]. EMBO Rep,2020,21:e48052.doi:10.15252/embr.201948052.
[13] Lu D,Chen B,Liang Z,et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind,randomized,controlled trial[J]. Diabetes Res Clin Pract,2011,92: 26-36.
[14] Mohamed SA,Howard L,McInerney V,et al. Autologous bone marrow mesenchymal stromal cell therapy for “no-option” critical limb ischemia is limited by karyotype abnormalities[J]. Cytotherapy,2020,22: 313-321.
[15] Gupta PK,Chullikana A,Parakh R,et al. A double blind randomized placebo controlled phase Ⅰ/Ⅱ study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia[J]. J Transl Med,2013,11: 143.doi:10.1186/1479-5876-11-143.
[16] Gupta PK,Shivashankar P,Rajkumar M,et al. Label extension,single-arm,phase Ⅲ study shows efficacy and safety of stempeucel in patients with critical limb ischemia due to atherosclerotic peripheral arterial disease[J]. Stem Cell Res Ther,2023,14:60.doi:10.1186/s13287-023-03292-w.
[17] Fujita Y,Kawamoto A. Stem cell-based peripheral vascular regeneration[J]. Adv Drug Deliv Rev,2017,120:25-40.
[18] Bura A,Planat-Benard V,Bourin P,et al.Phase Ⅰ trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia[J].Cytotherapy,2014,16: 245-257.
[19] Soria-Juan B,Garcia-Arranz M,Llanos Jiménez L,et al.Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase Ⅱ clinical trial (The NOMA Trial). Trials,2021,22:595.doi:10.1186/s13063-021-05430-2.
[20] Ashoobi MT,Hemmati H,Aghayan HR,et al. Wharton's jelly mesenchymal stem cells transplantation for critical limb ischemia in patients with type 2 diabetes mellitus: a preliminary report of phase I clinical trial[J]. Cell Tissue Res,2024,395:211-220.
[21] Shirbaghaee Z,Heidari Keshel S,Rasouli M,et al. Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI)[J]. Stem Cell Res Ther,2023,14:174.doi:10.1186/s13287-023-03390-9.
[22] Kwiatkowski T,Zbierska-Rubinkiewicz K,Krzywon JW,et al. Combined intra-arterial and intra-muscular transfer of Wharton's jelly mesenchymal stem/stromal cells in no-option critical limb ischemia-CIRCULATE N-O CLI pilot study[J]. Postep Kardiol Inter,2022,18:439-445.
[23] Zahavi-Goldstein E,Blumenfeld M,Fuchs-Telem D,et al.Placenta-derived PLX-PAD mesenchymal-like stromal cells are efficacious in rescuing blood flow in hind limb ischemia mouse model by a dose- and site-dependent mechanism of action[J].Cytotherapy,2017,19: 1438-1446.
[24] Norgren L,Weiss N,Nikol S,et al.PACE: randomized,controlled,multicentre,multinational,phase Ⅲ study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial[J].Br J Surg,2024,111: znad437.doi:10.1093/bjs/znad437.
[25] Arango-Rodríguez ML,Mateus LC,Sossa CL,et al. A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autolog-ous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells[J]. Stem Cell Res Ther,2023,14:221.doi:10.1186/s13287-023-03427-z.

间充质干细胞治疗慢性肢体威胁性缺血的临床研究进展

Clinical research progress on mesenchymal stem cells in the treatment of chronic limb-threatening ischemia

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