Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair.

Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self-repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases.

Nanostructure of collagen fibrils in human nucleus pulposus and its correlation with macroscale tissue mechanics.

Collagen fibrils are the main structural components of the nucleus pulposus tissue in the intervertebral discs. The structure-property relationship of the nucleus pulposus (NP) tissues is still unclear. We investigated the structure of individual collagen fibrils of the NP and evaluated its correlation with the bulk mechanical properties of the tissue. Collagen fibrils were extracted from the NP of discs retrieved from adolescents during scoliosis correction surgery, and the extracts were confirmed by SDS-PAGE. The diameters of the individual collagen fibrils were measured through atomic force microscopy, and the compressive mechanical properties of the tissues were evaluated by confined compression. The correlations between the nanoscale morphology of the collagen fibrils and the macroscale mechanical properties of the tissues were evaluated by linear regression. The SDS-PAGE results showed that the fibril extracts were largely composed of type II collagen. The mean diameter of the collagen fibrils was 92.1 +/- 26.54 nm; the mean swelling pressure and compressive modulus of the tissues were 6.15 +/- 4.3 kPa and 1.23 +/- 0.7 MPa, respectively. The mean fibril diameter had no linear correlation (R(2) = 0.30) with the swelling pressure of the tissues. However, it had a mild linear correlation with the compressive modulus (p = 0.023, R(2) = 0.68). This is the first study, to our knowledge, to evaluate the nanostructure of the individual collagen fibrils of the nucleus pulposus and its relationship with macroscale mechanical properties of the NP tissues.

Effect of iliac screw insertion depth on the stability and strength of lumbo-iliac fixation constructs: an anatomical and biomechanical study.

STUDY DESIGN: Comparison of feasibility and safety of the placement of short and long iliac screws by anatomic and biomechanical evaluations as they apply to lumbo-iliac fixation construct. OBJECTIVE: To compare the stability of the short and long iliac screw fixations for lumbo-iliac reconstruction by anatomic and biomechanical evaluations. SUMMARY OF BACKGROUND DATA: Spinopelvic reconstruction remains a challenge to spine surgeons. Despite the advent of many fixation methods, the use of iliac screws seems most favorable so far. Various lengths of iliac screws are applied in surgical treatments; however, no biomechanical comparison has been reported based on the screw length. METHODS: For anatomic observation, CT scan data of 60 Chinese adults were used to measure the details of the iliac spine structures. For biomechanical evaluation, 7 adult human cadavers (L3-pelvis) were observed. L4-S1 pedicle screw fixation was performed with posterior spinal fixation system. On the basis of the lengths of iliac screws, 2 groups were tested (short screw group using 70 mm screws and long screw group using 138 mm screws). In this study, short and long iliac screws were placed in the same specimen. Biomechanical testing was performed on a material testing machine under 800 N compression and 7 Nm torsion loading modes for stiffness evaluations. Finally, pullout testing was performed for all the iliac screws to measure the maximum pullout force. RESULTS: The length of the line between posterior superior iliac spine and anterior inferior iliac spine was 140.6 +/- 1.1 mm, and the distance between this line and the greater sciatic notch was 18.3 +/- 0.8 mm. The length of the line between posterior superior iliac spine and the second narrowest point was 67.1 +/- 0.62 mm in men and 70.1 +/- 1.4 mm in women. Insertion lengths of the short and long iliac screws were 70 +/- 2 mm and 138 +/- 4 mm, respectively. The lumbo-pelvic reconstruction using short and long iliac screws restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing respectively. In torsion testing, the use of short and long iliac screws harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial stiffness, respectively. No significant difference was detected between the 2 reconstructions in terms of compressive and torsional stiffness (P > 0.05). However, the maximum pullout strength of long iliac screw group was significantly higher than the short screw group (P < 0.05). CONCLUSION: The local stability is rather difficult to be restored to the original levels regardless the length of iliac screws. Obviously, long iliac screws resisted significantly greater axial pullout force. However, under physiologic, torsional, and compressive loading conditions, the mechanical stability of lumbo-pelvic fixation construct with short iliac screws was comparable with that of the long ones. Therefore, the use of short iliac screws, which are only about half the length of the long iliac screws, could reduce the implantation risk without significantly compromising on the stability of the construct.

Comparison of reliability between the PUMC and Lenke classification systems for classifying adolescent idiopathic scoliosis.

STUDY DESIGN: Comparison of 2 radiographic scoliosis classification systems by multiple surgeons. OBJECTIVE: Compare the reliability of Peking Union Medical College (PUMC) and Lenke scoliosis classification systems and analyze their differences. SUMMARY OF BACKGROUND DATA: The PUMC classification is a newly reported system based on radiographic measurements with recent popularity, while the Lenke classification is widely accepted worldwide in surgical design. Both these classification systems have their own individual characteristics, hence it is necessary to compare their reliability. METHODS: Five scoliosis surgeons independently evaluated and classified presurgical radiographs of 62 adolescent idiopathic scoliosis patients based on the PUMC and Lenke classification systems on 2 separate occasions. Radiographs were cleaned before each evaluation. Inter- and intraobserver reliabilities were quantified using Kappa statistics. Data were compared using chi2 analysis. RESULTS: The PUMC classification's inter- and intraobserver percentage of agreement averaged to 91.0% (Kappa coefficient 0.896) and 90.2% (Kappa coefficient 0.892), respectively. While those of the Lenke curve type classification were 86.5% (Kappa coefficient 0.808) and 87.4% (Kappa coefficient 0.826). The PUMC classification from 10 individual measurements had 17 cases (27.4%) of disagreements, while in the Lenke curve type classification, 24 cases (38.7%) had disagreements. PUMC classification normally has discrepancies between type IIb, IIc, and IId, while Lenke classification has discrepancies in curve types 1 and 2. Out of 17 inconsistent PUMC curve type cases, 7 did not affect surgical fusion levels, while in the Lenke's only 2 out of 24 cases with discrepancies did not affect fusion range selection, with an obvious statistical difference. CONCLUSION: The reliability of both PUMC classification and Lenke curve type classification were categorized as good-to-excellent. PUMC classification is relatively simple, with less confusion among inter- and intraobservers, with corresponding surgical fusion guidance and planning. The mismatch of curve classification had less influence on PUMC's fusion range selection than Lenke's.

Expression of the Trp2 allele of COL9A2 is associated with alterations in the mechanical properties of human intervertebral discs.

STUDY DESIGN: Biomechanical study into the association between genetic polymorphism in COL9A2 and mechanical properties of human nucleus pulposus. OBJECTIVE: To examine whether there is an association between genetic polymorphism in a structural gene, and alterations in the mechanical properties of the intervertebral discs that may predispose to disc degeneration. SUMMARY OF BACKGROUND DATA: Genetic studies have demonstrated that a polymorphism (Trp2 allele) in COL9A2 coding for alpha2 chain of collagen IX predisposes the individual to disc degeneration. The mechanism of this predisposition is not known. METHODS: Blood and whole disc samples were retrieved from adolescents and young adults during scoliosis surgery, degenerated discs were retrieved from patients with back pain during anterior spinal fusion. Anulus fibrosus and nucleus pulposus from a set of the scoliosis discs were used to perform immunohistochemistry to demonstrate the presence of collagen IX in the scoliosis discs. For the remaining samples, DNA was extracted from blood to determine the Trp2 status by sequencing. Nondegenerated (Trp2-), nondegenerated (Trp2+), and degenerated (Trp2-) nucleus pulposus samples were tested in confined compression. Swelling pressure and compressive modulus were measured and compared between groups. RESULTS: Positive staining of collagen IX was detected in both anulus fibrosus and nucleus pulposus sections confirming its presence in the scoliosis discs. The mean swelling pressure and compressive modulus values of 6 nondegenerated (Trp2+) samples (swelling pressure = 0.0019 MPa, compressive modulus = 0.97 MPa) were significantly lower (P < 0.05) than those of the 6 nondegenerated (Trp2-) samples (swelling pressure = 0.015 MPa; compressive modulus = 1.89 MPa). CONCLUSION: This is the first study to demonstrate an association between the Trp2 allele and disc mechanics, thus relating genetic variations and debilitating mechanical alterations that may ultimately result in intervertebral disc degeneration.