Takahara Eisaku, Kamizato Kota, Kakinohana Manabu, Sunami Hiroshi, Kise Yuya, Furukawa Kojiro, Ntege Edward Hosea, Shimizu Yusuke
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Regen Ther. 2024 Aug 21;26:611-619. doi: 10.1016/j.reth.2024.08.005. eCollection 2024 Jun.
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.
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.
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.
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.
胸腹围手术期脊髓缺血再灌注损伤（SCII/R）可导致严重的截瘫，这突出表明迫切需要有效的干预措施。然而，我们对最佳医学策略及其疗效的了解仍然有限。临床前研究表明，利用成体干细胞，包括多能和多能干细胞，如间充质干细胞（MSCs），通过增强神经炎症、轴突生长和髓鞘形成来解决SCII/R问题具有前景。特别是，来自脂肪组织来源的间充质干细胞（ADSCs）的生长因子已被提出有助于恢复。尽管取得了进展，但实现完全恢复仍然是一项艰巨的挑战。因此，更深入地了解ADSCs在减轻SCII/R诱导的截瘫中的作用，包括优化治疗的递送系统，势在必行。
在本研究中，我们使用短暂性主动脉闭塞诱导的大鼠SCII/R模型（即Taira-Marsala模型），评估了软膜下异体大鼠脂肪组织来源的间充质干细胞（rADSCs）移植对截瘫的影响。rADSCs从雄性Sprague-Dawley大鼠的脂肪组织中分离、培养、鉴定并冷冻保存。截瘫诱导一周后，移植rADSCs（n = 6）或生理盐水（n = 6）。在治疗前以及治疗后3天、7天和14天使用Basso-Beattie-Bresnahan评分系统评估后肢运动功能。
与生理盐水治疗组相比，rADSC治疗组后肢运动功能有显著改善（p < 0.05），6只大鼠中有5只在治疗后运动功能增强。
我们的研究结果表明，软膜下rADSC植入可能增强SCII/R诱导的截瘫恢复。这些初步结果推动进一步研究以验证这种潜力、了解分子机制并优化治疗方法。
