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使用 LOCAS-iPSCs-NSCs 促进 SCI 大鼠的神经再生和运动功能恢复。

Promotion of nerve regeneration and motor function recovery in SCI rats using LOCAS-iPSCs-NSCs.

机构信息

Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China.

Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopaedic Diseases, Liaoning Province, Dalian, 116011, Liaoning Province, China.

出版信息

Stem Cell Res Ther. 2024 Oct 23;15(1):376. doi: 10.1186/s13287-024-03999-4.

DOI:10.1186/s13287-024-03999-4
PMID:39444002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11515548/
Abstract

BACKGROUND

Spinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model.

METHODS

The rats underwent a complete transection SCI resulting in a 3-mm break at either the T9 or T10 level of the spinal cord.

RESULTS

Scanning electron microscope analysis revealed a uniform pore structure on the coronal plane of the scaffold. The LOCAS had a porosity of 88.52% and a water absorption of 1161.67%. Its compressive modulus and stress were measured at 4.1 MPa and 205 kPa, respectively, with a degradation time of 10 weeks. After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2). The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups. Motor evoked potentials latency was lower and amplitude was higher in the LOCAS-iPSCs-NSCs group, indicating better neural function recovery. Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats. The LOCAS scaffold facilitated ordered neurofilament extension and guided nerve regeneration.

CONCLUSIONS

The combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.

摘要

背景

脊髓损伤（SCI）是一种严重的创伤性脊髓疾病，预后较差。在这项研究中，我们创建了一种名为线性有序胶原聚集物（LOCAS）的支架，并将其负载诱导多能干细胞（iPSCs）衍生的神经干细胞（NSCs），这些 NSCs 来自人脐带来源的间充质干细胞（hUCB-MSCs），以治疗大鼠 SCI 模型。

方法

大鼠接受完全横断性 SCI 手术，导致脊髓 T9 或 T10 水平出现 3mm 的断裂。

结果

扫描电子显微镜分析显示支架冠状面上有均匀的孔结构。LOCAS 的孔隙率为 88.52%，吸水率为 1161.67%。其压缩模量和应力分别为 4.1 MPa 和 205 kPa，降解时间为 10 周。12 周后，LOCAS-iPSCs-NSCs 组大鼠 BBB 评分（8.6）明显高于 LOCAS-iPSCs-NSCs 组（5.6）和模型组（4.2）。CatWalk 分析显示，LOCAS-iPSCs-NSCs 组大鼠的运动轨迹、规则指数（RI）和摆动速度较其他组有所改善。LOCAS-iPSCs-NSCs 组大鼠的运动诱发电位潜伏期较低，振幅较高，表明神经功能恢复较好。组织学分析显示，LOCAS-iPSCs-NSCs 促进了 NSCs 的神经元分化和神经纤维再生，从而改善了大鼠的运动功能恢复。LOCAS 支架促进了神经纤维的有序延伸和神经再生。

结论

LOCAS 与 iPSCs-NSCs 的联合应用对 SCI 大鼠的运动功能恢复和组织修复具有积极的治疗作用。这一发展为 SCI 修复提供了更具弹性的仿生微环境，并为临床 SCI 修复带来了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7283/11515548/ca0236ef4600/13287_2024_3999_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7283/11515548/f86d640bd8d2/13287_2024_3999_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7283/11515548/6922ef71ac25/13287_2024_3999_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7283/11515548/125652b0d110/13287_2024_3999_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7283/11515548/ca0236ef4600/13287_2024_3999_Fig6_HTML.jpg

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