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包被在聚偏二氟乙烯膜(PFM)上的毛囊相关多能(HAP)干细胞促进脊髓损伤后的功能恢复。

Hair-Follicle-Associated Pluripotent (HAP) Stem Cells Encapsulated on Polyvinylidene Fluoride Membranes (PFM) Promote Functional Recovery from Spinal Cord Injury.

机构信息

Department of Dermatology, Kitasato University School of Medicine, Minami Ward, Sagamihara, 252-0374, Japan.

Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA.

出版信息

Stem Cell Rev Rep. 2019 Feb;15(1):59-66. doi: 10.1007/s12015-018-9856-3.

Abstract

Our previous studies showed that nestin-expressing hair follicle-associated-pluripotent (HAP) stem cells, which reside in the bulge area of the hair follicle, could restore injured nerve and spinal cord and differentiate into cardiac muscle cells. Here we transplanted mouse green fluorescent protein (GFP)-expressing HAP stem-cell colonies enclosed on polyvinylidene fluoride membranes (PFM) into the severed thoracic spinal cord of nude mice. After seven weeks of implantation, we found the differentiation of HAP stem cells into neurons and glial cells. Our results also showed that PFM-captured GFP-expressing HAP stem-cell colonies assisted complete reattachment of the thoracic spinal cord. Furthermore, our quantitative motor function analysis with the Basso Mouse Scale for Locomotion (BMS) score demonstrated a significant improvement in the implanted mice compared to non-implanted mice with a severed spinal cord. Our study also showed that it is easy to obtain HAP stem cells, they do not develop teratomas, and do not loose differentiation ability when cryopreserved. Collectively our results suggest that HAP stem cells could be a better source compared to induced pluripotent stem cells (iPS) or embryonic stem (ES) cells for regenerative medicine, specifically for spinal cord repair.

摘要

我们之前的研究表明,巢蛋白表达的毛囊相关多能(HAP)干细胞存在于毛囊的隆起部位,能够修复受损的神经和脊髓,并分化为心肌细胞。在这里,我们将聚偏二氟乙烯膜(PFM)包裹的绿色荧光蛋白(GFP)表达的 HAP 干细胞集落移植到裸鼠的胸段脊髓切断部位。移植 7 周后,我们发现 HAP 干细胞分化为神经元和神经胶质细胞。我们的结果还表明,PFM 捕获的 GFP 表达的 HAP 干细胞集落有助于胸段脊髓的完全再附着。此外,我们使用 Basso 小鼠运动评分(BMS)进行的定量运动功能分析表明,与未植入脊髓切断的非植入小鼠相比,植入小鼠的运动功能有显著改善。我们的研究还表明,与诱导多能干细胞(iPS)或胚胎干细胞(ES)相比,HAP 干细胞更容易获得,不会形成畸胎瘤,并且在冷冻保存时不会失去分化能力。综上所述,HAP 干细胞可能是再生医学,特别是脊髓修复的更好来源。

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