Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Hodges, Paul W.; James, Gregory; Blomster, Linda V.; Hall, Leanne; Schmid, Annina B.; Shu, Cindy; Little, Christopher B.; Melrose, James

doi:10.1097/brs.0000000000000972

Cited by 124 publications

(195 citation statements)

References 109 publications

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…No other model of disc degeneration has received such a comprehensive appraisal as the ovine model. The DDD which develops in the sheep model also effects multifidus muscle remodeling that may also contribute to LBP . Experimental DDD changes multifidus pro‐inflammatory cytokine gene expression profiles and mimics LBP changes in human spinal tissues .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background Forty percent of low back pain cases are due to intervertebral disc degeneration (IVDD), with mesenchymal stem cells (MSCs) a reported treatment. We utilized an ovine IVDD model and intradiscal heterologous MSCs to determine therapeutic efficacy at different stages of IVDD. Methodology Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6 × 20 mm annular lesions were made at three spinal levels using customized blades/scalpel handles, and IVDD was allowed to develop for 4 weeks in the Early (EA) and late Acute (LA) groups, or 12 weeks in the chronic (EST) group. Lesion IVDs received injections of 10 × 10 6 MSCs or PBS, and after 8 (EA), 22 (LA) or 14 (EST) weeks recuperation the sheep were sacrificed. Longitudinal lateral radiographs were used to determine disc heights. IVD glycosaminoglycan (GAG) and hydroxyproline contents were quantified using established methods. An Instron materials testing machine and customized jigs analyzed IVD (range of motion, neutral zone [NZ] and stiffness) in flexion/extension, lateral bending and axial rotation. qRTPCR gene profiles of key anabolic and catabolic matrix molecules were undertaken. Toluidine blue and hematoxylin and eosin stained IVD sections were histopathologically scoring by two blinded observers. Results IVDD significantly reduced disc heights. MSC treatment restored 95% to 100% of disc height, maximally improved NZ and stiffness in flexion/extension and lateral bending in the EST group, restoring GAG levels. With IVDD qRTPCR demonstrated elevated catabolic gene expression ( MMP2/3/9/13, ADAMTS4/5 ) in the PBS IVDs and expession normalization in MSC‐treated IVDs. Histopathology degeneracy scores were close to levels of NOC IVDs in MSC IVDs but IVDD developed in PBS injected IVDs. Discussion Administered MSCs produced recovery in degenerate IVDs, restored disc height, composition, biomechanical properties, down regulated MMPs and fibrosis, strongly supporting the efficacy of MSCs for disc repair.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Spinal manipulation studies demonstrate annular lesions influence IVD biomechanics, neurophysiological responses, vertebral lumbar motion segment responses, muscular contributions to dynamic dorsoventral lumbar spinal stiffness and three-dimensional vertebral motion in lumbar spinal motion segments. Multifidus muscle remodeling [33,120,121,122,123,124,125,126,127,128] in response to DDD may also be a source of LBP. Changes in multifidis pro-inflammatory cytokine gene expression [127] occur in response to experimental DDD [70].…”

Section: Discussionmentioning

confidence: 99%

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

Shu

Smith

et al. 2017

IJMS

Self Cite

View full text Add to dashboard Cite

The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs.

show abstract

“…For example, fatty atrophic changes have been observed in whole muscle imaging studies of the multifidus in individuals with chronic degenerative lumbar spine pathology compared to healthy controls . Similarly, decreased single fiber cross sectional areas (CSA's) have been observed with histology, although there are conflicting reports, and the changes are small . Furthermore, the majority of literature investigating histological features of LBP has focused on fiber type specific changes, which suggest selective atrophy of type II fibers and a shift in fiber type from oxidative to glycolytic .…”

mentioning

confidence: 99%

Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology

Shahidi

Hubbard

Gibbons

et al. 2017

Journal Orthopaedic Research

104

View full text Add to dashboard Cite

Histological and cell-level changes in the lumbar musculature in individuals with chronic lumbar spine degenerative conditions are not well characterized. Although prior literature supports evidence of changes in fiber type and size, little information exists describing the tissue quality and biology of pathological features of muscle in this population. The purpose of this study was to quantify multifidus tissue composition and structure, inflammation, vascularity, and degeneration in individuals with chronic degenerative lumbar spine pathology. Human multifidus biopsies were acquired from 22 consecutive patients undergoing surgery for chronic degenerative lumbar spine pathology. Relative fractions of muscle, adipose, and extracellular matrix were quantified along with muscle fiber type and cross-sectional area (CSA) and markers of inflammation, vascularity, satellite cell density, and muscle degeneration. On average, multifidus biopsies contained 48.5% muscle, 11.7% adipose tissue, and 26.1% collagen tissue. Elevated inflammatory cell counts (48.5 ± 30.0 macrophages/mm2) and decreased vascularity (275.6 ± 69.4 vessels/mm2) were also observed compared to normative values. Satellite cell densities were on average 13 ± 9 cells per every 100 muscle fibers. Large fiber CSA (3,996.0 ± 1,909.2 um2) and a predominance of type I fibers (61.8 ± 18.0%) were observed in addition to evidence of pathological degeneration-regeneration cycling (18.8 ± 9.4% centrally nucleated fibers, and 55.2 ± 24.2% of muscle regions containing degeneration). High levels of muscle degeneration, inflammation, and decreased vascularity were commonly seen in human multifidus biopsies of individuals with lumbar spine pathology in comparison to normative data. Evidence of active muscle degeneration suggests that changes in muscle tissue are more complex than simple atrophy.

show abstract

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Abstract: N/A.

Cited by 124 publications

References 109 publications

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology

Contact Info

Product

Resources

About