Subpial transplantation of adipose-derived stem cells alleviates paraplegia in a rat model of aortic occlusion/reperfusion-induced spinal cord infarction

脂肪干细胞软膜下移植可缓解主动脉闭塞/再灌注诱发的脊髓梗塞大鼠模型中的截瘫

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作者:Eisaku Takahara, Kota Kamizato, Manabu Kakinohana, Hiroshi Sunami, Yuya Kise, Kojiro Furukawa, Edward Hosea Ntege, Yusuke Shimizu

Background

Thoracoabdominal periprocedural occlusion/reperfusion injury of the spinal cord (SCII/R) can lead to devastating paraplegia, underscoring the critical need for effective interventions. However, our knowledge of optimal medical strategies and their efficacy remains limited. Preclinical investigations have shown promise in harnessing adult stem cells, including pluripotent and multipotent stem cells such as mesenchymal stem cells (MSCs), to address SCII/R by enhancing neuro-inflammation, axonal growth, and myelination. Particularly, growth factors derived from adipose tissue-derived MSCs (ADSCs) have been proposed to facilitate recovery. Despite advancements, achieving complete recovery remains a formidable challenge. Therefore, gaining a more profound insight into the role of ADSCs in alleviating SCII/R-induced paraplegia, including optimizing the delivery systems for therapies, is imperative. Materials and

Conclusions

Our findings suggest that subpial rADSC engraftment may enhance SCII/R-induced paraplegia recovery. These initial results drive further research to validate this potential, understand the molecular mechanisms, and optimize therapies.

Methods

In this study, we assessed the impact of subpial allogeneic rat adipose tissue-derived MSCs (rADSCs) transplantation on paraplegia using a rat SCII/R model induced by ephemeral aortic occlusion, known as the Taira-Marsala model. rADSCs were isolated from adipose tissue of male Sprague-Dawley rats, cultured, characterized, and cryopreserved. One week following the induction of paraplegia, rADSCs (n = 6) or physiological saline (n = 6) were transplanted. Hind limb motor function was evaluated before treatment and at 3-, 7-, and 14-days post-treatment using the Basso-Beattie-Bresnahan scoring system.

Results

The rADSC-treated group demonstrated a significant improvement in hind limb motor function compared to the saline-treated group (p < 0.05), with 5 out of 6 rats exhibiting enhanced motor function following treatment. Conclusions: Our findings suggest that subpial rADSC engraftment may enhance SCII/R-induced paraplegia recovery. These initial results drive further research to validate this potential, understand the molecular mechanisms, and optimize therapies.

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