Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus

Li, Xiaohe; Zhang, Yunfeng; Song, Bing; He, Erkai; Gao, Shang; Zhang, Shaojie; Cai, Yongqiang; Li, Zhijun; Li, Cunbao; Wang, Weiping; Wang, Xing; Wang, Haiyan; Wang, Zhiqiang; Zhang, Qi; Ma, Jierong

doi:10.12659/msm.898062

Cited by 14 publications

(7 citation statements)

References 6 publications

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“…Disc height and extracellular matrix (ECM) compositions were improved, but their study could not establish native AF architectural organization. Li et al compared dexamethasone treatment to dexamethasone and bone marrow‐derived mesenchymal cell treatment for AF defect rabbit model created by AF puncture and nucleotomy. Their results similarly indicated improved DHI maintenance and enhanced type II collagen content for the cellular treated group.…”

Section: Discussionmentioning

confidence: 99%

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

et al. 2019

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In recent years, studies have explored novel approaches for cell transplantation to enable annulus fibrosus (AF) regeneration of the intervertebral disc in particular for lumbar disc herniation. Nevertheless, successful engraftment of cells is structurally challenging, and no definitive method has yet been established. This study investigated the potential of cell sheet technology to facilitate cell engraftment for AF repair. AF injury was induced by a 1 × 1 mm defect in rat tails after which AF cell sheets were transplanted. Its regenerative effects were compared to a nondegenerated and degeneration only conditions. Degenerative changes of the entire intervertebral disc were examined by disc height measurements, histology, and immunohistochemistry for 4‐, 8‐, and 12‐weeks post‐transplantation. Cell engraftment was confirmed by tracing PKH26 fluorescent dyed AF cells. In the transplant group, disc degeneration was significantly suppressed after 4, 8, and 12 weeks when compared with the degenerative group, as indicated by histological scoring and DHI observations. At 2 and 4 weeks after transplant, PKH26 positive cells could be detected in defect region and surrounding AF. The results suggest cell engraftment into AF tissue could be established by the cell sheet technology without additional scaffolding or adhesives. In short, AF cell sheets appear to be an effective and accessible tool for AF repair and to support intervertebral disc regeneration.

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Section: Discussionmentioning

confidence: 99%

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

et al. 2019

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“…IVD heights were determined 2, 7 and 10 weeks after lesion induction and the affected IVDs were subjected to histopathological scoring. The authors considered BMMSCs were beneficial for what they considered to be annular repair . Pirvu et al used an interesting combination of BMMSCs seeded in polytrimethylene carbonate (PTMC) scaffold to produce annular repair tissue in a bovine organ culture annulotomy model under dynamic load for 14 days.…”

Section: Discussionmentioning

confidence: 99%

“…The authors considered BMMSCs were beneficial for what they considered to be annular repair. 125 Interesting recent developments in bioscaffold design have resulted in production of CS containing scaffolds with the ability to direct MSC cell differentiation in-situ. in the context of tissue repair this can be used to promote the production of matrix components conducive to tissue repair.…”

Section: The Ovine Large Lesion Model Of Disc Degeneration and Lbpmentioning

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

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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.

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“…A number of studies have documented positive results with MSCs in disc repair [ 37 , 49 , 65 , 182 , 183 , 184 , 185 , 186 , 187 ] and this has also been the subject of a number of definitive reviews [ 26 , 58 , 188 , 189 , 190 , 191 ]. The results we obtained with MSCs in the ovine annular lesion model of experimental DD are therefore consistent with these earlier findings.…”

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

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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.

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Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus

Cited by 14 publications

References 6 publications

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

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

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