Transplantation of Cord Blood Mesenchymal Stem Cells as Spheroids Enhances Vascularization
Transplantation of Cord Blood Mesenchymal Stem Cells as Spheroids Enhances Vascularization
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DOI：
10.1089/ten.tea.2011.0640
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发表时间：
2012-10-01
影响因子：
4.1
通讯作者：
Kim, Byung-Soo
中科院分区：
文献类型：
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作者：
Bhang, Suk Ho;Lee, Seahyoung;Kim, Byung-Soo
尽管干细胞用于治疗缺血性疾病的治疗性用途的有希望的结果，移植到缺血区域的细胞的存活率差是破坏干细胞治疗功效的主要问题之一。脐带血单核细胞（CBMNC）是间充质干细胞（MSC）的替代来源，而没有来自骨髓或脂肪组织的MSC的缺点，例如痛苦和侵入性收获过程。在本研究中，我们研究了脐带血间充质干细胞（CBMSCs）的血管生成功效是否可以通过移植到小鼠后肢缺血模型中的球体来增强。采用悬滴法制备人CBMSC（hCBMSC）球。通过切除股动脉及其分支诱导小鼠后肢缺血。手术后，将动物分为未处理组、分离的hCBMSC组和球状体hCBMSC组（每组n = 8），并接受相应的hCBMSC处理。术后观察4周，取缺血后肢肌肉行组织学观察。在体外和/或体内研究了凋亡信号、血管生成相关信号通路和血管形成。将hCBMSCs作为球状体移植到小鼠缺血后肢中，通过抑制凋亡信号同时激活抗凋亡信号，显著改善了移植细胞的存活。此外，hCBMSCs作为球状体的移植显著增加了小鼠缺血肢体中微血管和平滑肌α-肌动蛋白阳性血管的数量，并减轻了肢体丧失和坏死。人CBMNC可以被认为是MSC的替代来源，并且基于球状体的hCBMSC递送可以被认为是用于增强hCBMSC的治疗功效的简单且有效的策略。
Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, the poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of cord blood mesenchymal stem cells (CBMSCs) can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging-drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, the animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n = 8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then, the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating antiapoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and smooth muscle alpha-actin-positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. Human CBMNC can be considered an alternative source of MSC, and spheroid-based hCBMSC delivery can be considered a simple and effective strategy for enhancing the therapeutic efficacy of hCBMSCs.