Repeated Administrations of human umbilical cord mesenchymal stem cells Promote Motor Function Recovery Correlated with Diffusion Tensor Imaging in Canine Model of Spinal Cord Injury

Abstract

Background and aims: Diffusion tensor imaging (DTI) has the advantage of revealing the subtle pathology of damaged spinal cord more clearly and comprehensively. However, no studies have systematically investigated the correlation between motor function recovery and dynamic changes of DTI parameters involving the whole spinal cord after repeated subarachnoid administration of human umbilical cord mesenchymal stem cells (hUC-MSCs) in a canine model of spinal cord injury (SCI). This study aimed to clarify it to quantitatively investigate DTI metrics as potential prognostic indicators for functional recovery of locomotion.
Materials and methods: Eight female beagle canines were subjected to thoracolumbar SCI, and then they received four times of intrathecal transplantation of hUC-MSCs from Week 2 (W2) to W5 (once per week). During the 15-week observation period, the motor function of the pelvic limb was assessed by using the OIby score system at each week. At W1, W8, and W15, DTI scanning rostrally, centrally, and caudally within the lesion site was performed, and then, multiple radiological parameters, including fractional anisotropy (FA), average diffusion coefficient, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD), were collected.
Results: Significant improvement of the OIby score was observed at the latest ten time points when compared with that at W1. FA rostrally, centrally, and caudally within the lesion site revealed a decreasing tendency, while all the other radiological indicators at these three regions had the N-shaped trend that showed an initial increase and subsequent decrease. Except for the comparisons between W15 and W1 regarding cranial MD, cranial RD, and caudal RD, the remaining comparisons of radiological data between W15 and W1 and all the DTI metrics between W8 and W1 demonstrated statistical significance. Pearson correlation analysis found that cranial FA (r = 0.723, P = 0.043) at W8, as well as both cranial AD (r = −0.761, P = 0.028) and MD (r = −0.728, P = 0.041) at W15 correlated with the final OIby score. Simple regression model (y = 26.178-4.176x, y: OIby score, x: cranial AD value) uncovered a negative linear correlation between rostral AD and locomotion performance both at W15 (R2 = 0.578, β = −0.761, P = 0.028).
Conclusions: Our work demonstrates that in a canine model of SCI receiving repeated intrathecal transplantation of hUC-MSCs, cranial FA at 3 weeks post-cytotherapy, as well as both cranial AD and MD at 10 weeks after hUC-MSC administration, were associated with final regaining of motor function, and rostral AD seems a feasible predictor of behavioral recovery. This study provides DTI clues in predicting sensorimotor function restoration in humans with SCI after repeated subarachnoid transplantation of hUC-MSCs.

Keywords

Spinal cord injury / Mesenchymal stem cell / Diffusion tensor imaging / Recovery of motor function / Prediction

CRediT authorship contribution statement

Limin Rong, Yang Yang, Bin Liu, Mao Pang, Liangming Zhang:Conceptualization. Yang Yang, Shaochuan Li, Huiquan Wen,Zhuang Kang: Resources and Methodology. Yang Yang, Liangming Zhang, Feng Feng: Investigation. Limin Rong, Yang Yang, Bin Liu, Mao Pang, Ziming Wang: Data Analysis. Limin Rong, Yang Yang, Bin Liu, Mao Pang, Liangming Zhang, Ruoqi Shen, Ziming Wang: Writing.

Ethics statement

The study was conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee of Sun Yat- Sen University and all protocols were approved by this committee (SYSU-IACUC-2018-000130). All animal experiment complied with the ARRIVE guidelines and were performed and based on the 3R principle (Reduction, Replacement and Refinement). The study was conducted in accordance with the local legislation and institutional requirements.

Consent for publication

Not applicable.

Data availability statement

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Funding

This work was supported by grants from the National Natural Science Foundation of China (U22A20297); Key Research and Development Program of Guangzhou (202206060003); Guangdong Basic and Applied Basic Research Foundation (2024A1515013070, 2025A1515012371); Cultivation Programme of National Natural Science Foundation of China (2023GZRPYMS04).

Declaration of competing interest

The authors declare that they have no conflicts of interest.

Acknowledgments

We deeply thank Lianxiong Yuan for performing the statistical analysis for this study.

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