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使用脂肪组织来源的干细胞和再生细胞修复椎间盘:犬模型实验。

Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model.

机构信息

Department of Orthopaedic Surgery, Atlanta Medical Center, Atlanta, GA 30312, USA.

出版信息

Spine (Phila Pa 1976). 2009 Oct 1;34(21):2297-304. doi: 10.1097/BRS.0b013e3181a54157.

Abstract

STUDY DESIGN

Therapeutic treatment of intervertebral disc repair using cells.

OBJECTIVE

The goal of the study was to test the hypothesis that repair of a damaged disc is possible using autologous adipose tissue derived stem and regenerative cells (ADRCs).

SUMMARY OF BACKGROUND DATA

Degradation resulting from either acute or chronic repetitive disc injury leads to disc degeneration. However, if a damaged disc could be repaired in the early stages, before the onslaught of degradation, then the disc degeneration process may be slowed down.

METHODS

Twelve dogs underwent a partial nucleotomy at 3 lumbar levels (L3-L4, L4-L5, and L5-L6); adjacent levels served as nonoperated controls. The animals (or discs) were allowed to recover from the surgery for 6 weeks. At that time subcutaneous adipose tissue was harvested and ADRCs were isolated. The 3 experimental discs that had undergone a partial nucleotomy were randomized to receive: (1) ADRCs in hyaluronic acid carrier (Cells/HA); (2) HA only; or (3) No Intervention. Assessments of the 3 experimental discs plus the 2 adjacent untouched discs were made using MRI, radiography, histology, and biochemistry. The animals were killed at 6 months and at 12 months.

RESULTS

Repair in this study was specifically demonstrated through histology and biochemical analysis. Disc levels receiving ADRCs more closely resembled the healthy controls as evidenced in matrix translucency, compartmentalization of the anulus, and in cell density within the nucleus pulposus. Matrix analysis for Type-II collagen and aggrecan demonstrated evidence of a statistically better regenerative stimulation to the disc provided by ADRCs when compared to either the HA only or no intervention treatments.

CONCLUSION

Autologous adipose tissue derived stem and regenerative cells, as used in this disc injury model, were effective in promoting disc regeneration, as evidenced by disc matrix production and overall disc morphology.

摘要

研究设计

使用细胞进行椎间盘修复的治疗。

研究目的

本研究旨在验证以下假设,即使用自体脂肪组织来源的干细胞和再生细胞(ADRCs)修复受损的椎间盘是可能的。

背景资料概要

无论是急性还是慢性反复性椎间盘损伤导致的退化,都会导致椎间盘退化。然而,如果在退化开始之前,即受损的椎间盘还处于早期阶段时对其进行修复,那么椎间盘退化的过程可能会减缓。

方法

12 只狗在 3 个腰椎水平(L3-L4、L4-L5 和 L5-L6)进行部分髓核切除术;相邻的水平作为非手术对照。动物(或椎间盘)在手术后允许恢复 6 周。此时,采集皮下脂肪组织并分离 ADRCs。对接受部分髓核切除术的 3 个实验椎间盘进行随机分组,分别接受以下处理:(1)ADRCs 在透明质酸载体中(细胞/HA);(2)仅 HA;或(3)无干预。使用 MRI、放射照相术、组织学和生物化学评估 3 个实验椎间盘和 2 个相邻未受影响的椎间盘。在 6 个月和 12 个月时处死动物。

结果

本研究通过组织学和生化分析具体证明了修复的存在。接受 ADRCs 治疗的椎间盘水平与健康对照组更为相似,表现在基质透明度、纤维环分区以及核髓核内细胞密度方面。与仅接受 HA 或无干预治疗相比,基质中 II 型胶原蛋白和聚集蛋白聚糖的分析表明,ADRCs 对椎间盘提供了更具统计学意义的再生刺激。

结论

在这种椎间盘损伤模型中使用的自体脂肪组织来源的干细胞和再生细胞,在促进椎间盘再生方面是有效的,这表现在椎间盘基质的产生和整体椎间盘形态上。

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