Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine.

Chronic spinal cord injury functionally repaired by direct implantation of encapsulated hair-follicle-associated pluripotent (HAP) stem cells in a mouse model: Potential for clinical regenerative medicine.
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DOI:
10.1371/journal.pone.0262755
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
Amoh Y
Amoh Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Obara K;Shirai K;Hamada Y;Arakawa N;Yamane M;Takaoka N;Aki R;Hoffman RM;Amoh Y

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慢性脊髓损伤(SCI)是一种高度衰弱和顽固性疾病,治疗选择有限。尽管各种类型的干细胞在损伤修复方面显示出一定的临床疗效,但它们对SCI没有疗效。毛囊相关多能干细胞(Hair-follicle-associated pluripotent,HAP)可分化为神经元、许旺细胞、搏动心肌细胞和许多其他类型的细胞,并在小鼠模型中有效再生急性脊髓损伤。在本报告中,来自C57 BL/6 J小鼠的HAP干细胞,封装在聚偏氟乙烯膜(PFM)中,植入C57 BL/6 J或无胸腺裸鼠在早期慢性阶段的切断的胸脊髓中。HAP干细胞移植于C57 BL/6 J和裸鼠胸髓后,可分化为神经元、星形胶质细胞和少突胶质细胞。用Basso小鼠运动量表(BMS)评分进行的定量运动功能分析表明,与未植入小鼠相比,植入HAP干细胞的小鼠功能显著改善。HAP干细胞具有优于其他干细胞的关键优势:它们不会发展成畸胎瘤;当冷冻保存时不会失去分化能力,因此是可储存的;是自体的,容易从任何人获得;并且不需要遗传操作。因此,HAP干细胞比诱导多能干细胞(iPSC)、神经元干细胞(NSC)/神经祖细胞(NPC)或胚胎干细胞(ESC)具有更大的SCI修复临床潜力。本报告显示了HAP干细胞修复慢性脊髓损伤的未来临床潜力,目前慢性脊髓损伤是一种难治性疾病。
Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.
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