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The Effect of Different Routes of Xenogeneic Mesenchymal Stem Cell Transplantation on the Regenerative Potential of Spinal Cord Injury

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Abstract

Purpose

Mesenchymal stem cell (MSC) transplantation has been touted as a possible treatment for spinal cord injury (SCI) patients’ locomotor and neurological rehabilitation. The intralesional injection of MSC is a typical delivery route for SCI, although this can result in further injury. We conducted the study with the aim of characterizing canine bone marrow–derived MSC (cBM-MSC) and evaluating the relative efficacy of different routes of cBM-MSC transplantation on regeneration of SCI in rabbits.

Methods

The cBM-MSCs were isolated, cultured, and characterized using an established protocol. The in vitro neuronal differentiation potential of the cBM-MSCs was examined by culturing them into neuronal differentiation medium. The spinal injury was created by epidural microballoon compression following a right microhemilaminectomy in thirty rabbits that were divided into five groups based on treatment: untreated sham control, vehicle control, and transplanted with cBM-MSCs through intravenous (IV), intralesional (IL), and intracisternal (IC) routes on the 24 h and 7th day post-injury. The efficacy of cBM-MSC transplantation was evaluated based on the hind limb function scoring and histopathology.

Results

The cBM-MSCs on characterization were found to be CD44-, CD90-, and CD105-positive, and CD45-negative. The differentiation was confirmed by immunocytochemistry, through which the specific marker β-tubulin III for the neurons was detected. The IC group had the best functional recovery, followed by the IL group, and the IV group had the worst. Histopathological findings of the spinal cord on days 30 and 60 correlated with the clinical findings.

Conclusions

The results indicated that the epidural microballoon compression following a right microhemilaminectomy was found to be minimally invasive and easily reproducible for the SCI model. Intracisternal transplantation of cBM-MSCs may be used for effective functional recovery of spinal injury.

Lay Summary

Herein, an optimal method to transplant MSC into the injured spinal cord to facilitate functional recovery was established in rabbits. The cBM-MSCs were isolated, cultured, and characterized. The in vitro neuronal differentiation of the cBM-MSCs was confirmed, and cultured cBM-MSCs were transplanted in rabbits with spinal injury. The efficacy of cBM-MSC transplantation was evaluated based on the hind limb function scoring and histopathology. Intracisternal transplantation was associated with the greatest functional improvement.

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Acknowledgements

The authors are thankful to Director ICAR-IVRI for providing all the facilities to carry out the present research work.

Funding

The study was funded by ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India, under the MVSc research program to the first author.

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Authors and Affiliations

  1. Division of Surgery, ICAR-Indian Veterinary Research Institute, Uttar Pradesh, Izatnagar, India

    A. Suvarna, M. Hoque, A. C. Saxena & Vineet Kumar

  2. Department of Veterinary Surgery and Radiology, College of Veterinary and Animal Sciences, Sardar Vallabhbhai Patel University of Agriculture and Technology, Uttar Pradesh, Meerut, India

    Vineet Kumar

  3. Division of Pathology, ICAR-Indian Veterinary Research Institute, Uttar Pradesh, Izatnagar, India

    Rajendra Singh

  4. Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Uttar Pradesh, Izatnagar, India

    Sadhan Bag

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  1. A. Suvarna
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by A. Suvarna, A. C. Saxena, Rajendra Singh, and Sadhan Bag. The first draft of the manuscript was written by Vineet Kumar and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vineet Kumar.

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Suvarna, A., Hoque, M., Saxena, A.C. et al. The Effect of Different Routes of Xenogeneic Mesenchymal Stem Cell Transplantation on the Regenerative Potential of Spinal Cord Injury. Regen. Eng. Transl. Med. 9, 407–415 (2023). https://doi.org/10.1007/s40883-022-00290-x

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