Allogeneic Mesenchymal Precursor Cells Promote Healing in Postero-lateral Annular Lesions and Improve Indices of Lumbar Intervertebral Disc Degeneration in an Ovine Model

Allogeneic Mesenchymal Precursor Cells Promote Healing in Postero-lateral Annular Lesions and Improve Indices of Lumbar Intervertebral Disc Degeneration in an Ovine Model
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DOI:
10.1097/brs.0000000000001528
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发表时间:
2016-09-01
期刊:
影响因子:
3
通讯作者:
Howell, Stuart
Howell, Stuart
中科院分区:
医学2区
文献类型:
--
作者:
Freeman, Brian J. C.;Kuliwaba, Julia S.;Howell, Stuart

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研究设计:椎间盘退变(IVD)的体内绵羊模型,以评估干细胞治疗。目的:确定干细胞注入退变腰椎IVD的髓核(NP)或纤维环(AF)是否能改善椎间盘健康指数。背景资料摘要:先前评估干细胞注射到退变IVD的疗效的研究报告了阳性结果。然而,研究一直局限于小动物,只针对NP,短期following.Methods。间充质前体细胞(MSC)从髂嵴的8周龄羊。在8只2岁绵羊的3个腰椎节段通过后外侧纤维环切开术诱导IVD变性。6个月后,每个退化的IVD被随机分配到三种治疗中的一种:(i)将MSC注射到先前切开的AF(AFI),(ii)NP(NPI),或(iii)不注射(阴性对照,NC)。相邻IVD接受磷酸盐缓冲盐水注射到NP(阳性对照,PC)中。在基线、6个月、9个月和12个月时获得X线片和磁共振成像扫描。12个月时收集椎间盘进行生物化学和组织学分析。结果:椎间盘高度指数(DHI)、椎间盘高度(DH)、糖胺聚糖(GAG)含量降低,椎间盘退变程度增加。与NC组相比,干细胞注射后6个月,AFI组和NPI组的DHI和DH恢复正常(P < 0.05)。
Study Design.In-vivo ovine model of intervertebral disc degeneration (IVD) to evaluate treatment with stem cells.Objective.To determine if stem cells delivered to the nucleus pulposus (NP) or the annulus fibrosus (AF) of degenerated lumbar IVDs leads to improved indices of disc health.Summary of Background Data.Previous studies assessing the efficacy of stem cell injections into degenerated IVDs have reported positive findings. However, studies have been limited to small animals, targeting solely the NP, with short term follow-up.Methods.Mesenchymal precursor cells (MSC) were obtained from the iliac crest of 8-week-old sheep. IVD degeneration was induced by postero-lateral annulotomy at three lumbar levels in eight 2-year-old sheep. Six months later, each degenerated IVD was randomized to one of three treatments: Injection of MSC into (i) previously incised AF (AFI), (ii) NP (NPI), or (iii) no injection (negative control, NC). The adjacent IVD received injection of phosphate buffered saline into NP (positive control, PC). Radiographs and magnetic resonance imaging scans were obtained at baseline, 6, 9, and 12 months. Discs were harvested at 12 months for biochemical and histological analyses.Results.IVD degeneration was consistently observed postannulotomy, and characterized by reduced disc height index (DHI), disc height (DH), glycosaminoglycan (GAG) content, and increased grade of disc degeneration.Six months after stem cell injection, DHI and DH had recovered in AFI and NPI groups when compared with NC group (P