Proffen Benedikt L, Vavken Patrick, Haslauer Carla M, Fleming Braden C, Harris Chad E, Machan Jason T, Murray Martha M
Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA
Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA Department of Orthopaedic Surgery, University Hospital Basel, Switzerland.
Am J Sports Med. 2015 Feb;43(2):320-30. doi: 10.1177/0363546514559826. Epub 2014 Dec 30.
Coculture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bioenhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix-based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bioenhanced ACL repair was investigated.
The addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bioenhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bioenhanced ACL repair after 15 weeks of healing.
Controlled laboratory study.
Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by (1) bioenhanced ACL repair, (2) bioenhanced ACL repair with the addition of autologous adipose-derived MSCs, and (3) bioenhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After 15 weeks of healing, the structural properties of the ACL (yield load, failure load, and linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the advanced Ligament Maturity Index.
After 15 weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior laxity when measured at 30° of flexion.
These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood before saturation of an extracellular matrix carrier with the blood did not improve the functional results of bioenhanced ACL repair after 15 weeks of healing in the pig model.
Whole blood represents a practical biologic additive to ligament repair, and any other additive (including stem cells) should be demonstrated to be superior to this baseline before clinical use is considered.
髌下脂肪垫间充质干细胞(MSCs)与外周血共培养已证实在体外可刺激前交叉韧带(ACL)成纤维细胞增殖及胶原蛋白生成。动物研究中目前生物增强ACL修复技术包括在韧带简单缝合修复基础上添加生物支架,在此情况下是一种用自体全血饱和的基于细胞外基质的支架。研究了用MSCs富集全血是否会进一步改善生物增强ACL修复的体内效果。
在用于生物增强ACL修复以促进愈合的血液-细胞外基质复合物中添加源自脂肪组织或外周血的MSCs,将改善愈合15周后生物增强ACL修复的生物力学性能。
对照实验室研究。
24只青春期尤卡坦小型猪接受ACL横断,随后进行(1)生物增强ACL修复,(2)添加自体脂肪来源MSCs的生物增强ACL修复,以及(3)添加自体外周血来源MSCs的生物增强ACL修复。愈合15周后,测量ACL的结构性能(屈服载荷、破坏载荷和线性刚度)。通过组织学测量修复后ACL中的细胞和血管密度,并使用先进的韧带成熟指数对其组织结构进行定性评估。
愈合15周后,添加脂肪来源MSCs在生物力学或组织学性能方面无显著改善。添加外周血MSCs的唯一显著变化是在30°屈曲时测量的膝关节前后松弛度增加。
这些发现表明,在用血液使细胞外基质载体饱和之前,向全血中添加脂肪或外周血MSCs并不能改善猪模型中愈合15周后生物增强ACL修复的功能结果。
全血是韧带修复的一种实用生物添加剂,在考虑临床应用之前,任何其他添加剂(包括干细胞)都应证明优于该基线。