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. 2020 May 6;3(2):e1091.
doi: 10.1002/jsp2.1091. eCollection 2020 Jun.

Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations

Obiajulu Agha  1   2 , Andreas Mueller-Immergluck  1   2 , Mengyao Liu  1   2 , He Zhang  1   2   3 , Alekos A Theologis  1   2 , Aaron Clark  4 , Hubert T Kim  1   2 , Xuhui Liu  1   2 , Brian T Feeley  1   2 , Jeannie F Bailey  1
Affiliations

Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations

Obiajulu Agha et al. JOR Spine. .

Abstract

Background: Paraspinal muscles are crucial for vertebral stabilization and movement. These muscles are prone to develop fatty infiltration (FI), fibrosis, and atrophy in many spine conditions. Fibro-adipogenic progenitors (FAPs), a resident muscle stem cell population, are the main contributors of muscle fibrosis and FI. FAPs are involved in a complex interplay with satellite cells (SCs), the primary myogenic progenitor cells within muscle. Little is known about the stem cell composition of the multifidus. The aim of this study is to examine FAPs and SCs in the multifidus in disc herniation patients. Multifidus muscle samples were collected from 10 patients undergoing decompressive spine surgery for lumbar disc herniation. Hamstring muscle was collected from four patients undergoing hamstring autograft ACL reconstruction as an appendicular control. Multifidus tissue was analyzed for FI and fibrosis using Oil-Red-O and Masson's trichrome staining. FAPs and SCs were visualized using immunostaining and quantified with fluorescence-activated cell sorting (FACS) sorting. Gene expression of these cells from the multifidus were analyzed with reverse transcription-polymerase chain reaction and compared to those from hamstring muscle. FI and fibrosis accounted for 14.2%± 7.4% and 14.8%±4.2% of multifidus muscle, respectively. The multifidus contained more FAPs (11.7%±1.9% vs 1.4%±0.2%; P<.001) and more SCs (3.4%±1.6% vs 0.08%±0.02%; P=.002) than the hamstring. FAPs had greater α Smooth Muscle Actin (αSMA) and adipogenic gene expression than FAPs from the hamstring. SCs from the multifidus displayed upregulated expression of stem, proliferation, and differentiation genes.

Conclusion: The multifidus in patients with disc herniation contains large percentages of FAPs and SCs with different gene expression profiles compared to those in the hamstring. These results may help explain the tendency for the multifidus to atrophy and form FI and fibrosis as well as elucidate potential approaches for mitigating these degenerative changes by leveraging these muscle stem cell populations.

Keywords: atrophy; fatty infiltration; fibrosis; fibro‐adipogenic progenitors; multifidus; paraspinal muscle; satellite cells.

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Conflict of interest statement

O. A., A. M. I., M. L., H. Z., H. T. K, X. L., B. T. F., and J. B. F., their immediate family, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this article. A. A. T. is a consultant for Alphatec and DePuy Spine, and participates in the development of educational content for the Journal of Bone and Joint Surgery, all of which are unrelated to the submitted work. A. C. is a consultant for NuVasive, unrelated to the submitted work.

Figures

FIGURE 1
FIGURE 1
Representative histology images of multifidus and hamstring muscle specimens, ×20 magnification. Left, Oil‐Red‐O(ORO) staining for fatty infiltration (red). Right, Masson's trichrome staining for fibrosis (blue/purple)
FIGURE 2
FIGURE 2
A, Full gating of FACS cell sorting. Gates were set based on each antibodies' FMO for every run. FAP and SC quantity were reported as a percentage of nondebris live cells. Sorting order is from top left to top right to bottom left to bottom right with the final FAP population defined as CD31‐/CD45‐/CD29‐/CD56‐/PDGFRα+/CD184‐, and final SC population defined as CD31‐/CD45‐/CD29+/CD56+/PDGFRα‐/CD184+. B, Forward and side scatter plots of final FAP and SC populations from the multifidus and hamstring. FAP, fibro‐adipogenic progenitor; FMO, fluorescence minus one; PDGFRα, platelet‐derived growth factor receptor alpha; SC, satellite cell
FIGURE 3
FIGURE 3
Percentages of FAPs (left) and SCs (right) within the multifidus and hamstring muscle as quantified using FACS cell sorting. FAP and SC quantity were reported as a percentage of non‐debris live cells. FAP, fibro‐adipogenic progenitor; SC, satellite cell
FIGURE 4
FIGURE 4
Representative immunostaining of multifidus and hamstring muscle demonstrating respective relative proportions of FAPs and SCs residing in the muscle, ×40 magnification, scale bar represents 20 μm. Red, PDGFRα ‐ FAP marker. Green, PAX7 ‐ SC marker. Blue, DAPI. Gray, laminin. FAP, fibro‐adipogenic progenitor; PDGFRα, platelet‐derived growth factor receptor alpha; SC, satellite cell
FIGURE 5
FIGURE 5
Comparative gene expression profile of FAPs from multifidus normalized to FAPs from hamstring. Gray bar designates fibrogenic gene expression. Black bars designate adipogenic gene expression. Y‐axis scale represents logarithmic fold difference. * denotes P < .05. FAP, fibro‐adipogenic progenitor
FIGURE 6
FIGURE 6
Comparative gene expression profile of SCs from multifidus normalized to SCs from hamstring. Gray bars designate stem/proliferation gene expression. Black bars designate differentiation gene expression. Y‐axis scale represents logarithmic fold difference. * denotes P < .05. SC, satellite cell
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