Literature DB >> 23384411

Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo.

Steven K Leckie1, Gwendolyn A Sowa, Bernard P Bechara, Robert A Hartman, Joao Paulo Coelho, William T Witt, Qing D Dong, Brent W Bowman, Kevin M Bell, Nam V Vo, Brian C Kramer, James D Kang.   

Abstract

BACKGROUND CONTEXT: Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery.
PURPOSE: To determine whether injecting human umbilical tissue-derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD.
DESIGN: Prospective, randomized, blinded placebo-controlled in vivo study. PATIENT SAMPLE: Skeletally mature New Zealand white rabbits. OUTCOME MEASURES: Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology.
METHODS: Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2-L3, L3-L4, and L4-L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4-L5 were analyzed histologically. The L3-L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated.
RESULTS: Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically significant difference from the punctured values. There were no statistically significant MRI differences among the three treatment groups. The treated groups also demonstrated viscoelastic properties that were distinct from the control and punctured values, with the cell curve more similar to the punctured curve and the carrier curve and carrier+cells curve more similar to the control curve (although no creep differences achieved statistical significance). There was some histological evidence of improved cellularity and disc architecture in the treated discs compared with the punctured discs.
CONCLUSIONS: Treatment of degenerating rabbit intervertebral discs with hUTC in a hydrogel carrier solution might help restore the MRI, histological, and biomechanical properties toward those of nondegenerated controls. Treatment with cells in saline or a hydrogel carrier devoid of cells also might help restore some imaging, architectural, and physical properties to the degenerating disc. These data support the potential use of therapeutic cells in the treatment of disc degeneration.
Copyright © 2013 Elsevier Inc. All rights reserved.

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Year:  2013        PMID: 23384411      PMCID: PMC4868072          DOI: 10.1016/j.spinee.2012.12.004

Source DB:  PubMed          Journal:  Spine J        ISSN: 1529-9430            Impact factor:   4.166


  46 in total

1.  Isolation of multipotent mesenchymal stem cells from umbilical cord blood.

Authors:  Oscar K Lee; Tom K Kuo; Wei-Ming Chen; Kuan-Der Lee; Shie-Liang Hsieh; Tain-Hsiung Chen
Journal:  Blood       Date:  2003-10-23       Impact factor: 22.113

2.  Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc.

Authors:  Daisuke Sakai; Joji Mochida; Toru Iwashina; Akihiko Hiyama; Hiroko Omi; Masaaki Imai; Tomoko Nakai; Kiyoshi Ando; Tomomitsu Hotta
Journal:  Biomaterials       Date:  2005-08-19       Impact factor: 12.479

3.  An injectable cross-linked scaffold for nucleus pulposus regeneration.

Authors:  Damien O Halloran; Sibylle Grad; Martin Stoddart; Peter Dockery; Mauro Alini; Abhay S Pandit
Journal:  Biomaterials       Date:  2007-10-23       Impact factor: 12.479

4.  Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans.

Authors:  Yin-Gang Zhang; Xiong Guo; Peng Xu; Long-Li Kang; Jun Li
Journal:  Clin Orthop Relat Res       Date:  2005-01       Impact factor: 4.176

5.  Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study.

Authors:  Lluis Orozco; Robert Soler; Carles Morera; Mercedes Alberca; Ana Sánchez; Javier García-Sancho
Journal:  Transplantation       Date:  2011-10-15       Impact factor: 4.939

6.  Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration.

Authors:  Daisuke Sakai; Joji Mochida; Toru Iwashina; Takuya Watanabe; Tomoko Nakai; Kiyoshi Ando; Tomomitsu Hotta
Journal:  Spine (Phila Pa 1976)       Date:  2005-11-01       Impact factor: 3.468

7.  Comparison of animal discs used in disc research to human lumbar disc: axial compression mechanics and glycosaminoglycan content.

Authors:  Jesse C Beckstein; Sounok Sen; Thomas P Schaer; Edward J Vresilovic; Dawn M Elliott
Journal:  Spine (Phila Pa 1976)       Date:  2008-03-15       Impact factor: 3.468

8.  Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration.

Authors:  Alexander Abbushi; Michaela Endres; Mario Cabraja; Stefan Nicolas Kroppenstedt; Ulrich Wilhelm Thomale; Michael Sittinger; Aldemar Andres Hegewald; Lars Morawietz; Arne-Jörn Lemke; Victor-Götz Bansemer; Christian Kaps; Christian Woiciechowsky
Journal:  Spine (Phila Pa 1976)       Date:  2008-06-15       Impact factor: 3.468

Review 9.  Critical analysis of trends in fusion for degenerative disc disease over the past 20 years: influence of technique on fusion rate and clinical outcome.

Authors:  Christopher M Bono; Casey K Lee
Journal:  Spine (Phila Pa 1976)       Date:  2004-02-15       Impact factor: 3.468

10.  Amidic alginate hydrogel for nucleus pulposus replacement.

Authors:  Gemma Leone; Paola Torricelli; Antonio Chiumiento; Alessandro Facchini; Rolando Barbucci
Journal:  J Biomed Mater Res A       Date:  2008-02       Impact factor: 4.396

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  27 in total

1.  A future in our past: the umbilical cord for orthopaedic tissue engineering.

Authors:  Antonio Marmotti; Giuseppe Maria Peretti; Silvia Mattia; Davide Edoardo Bonasia; Matteo Bruzzone; Federico Dettoni; Roberto Rossi; Filippo Castoldi
Journal:  Joints       Date:  2014-05-08

Review 2.  Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.

Authors:  Daisuke Sakai; Gunnar B J Andersson
Journal:  Nat Rev Rheumatol       Date:  2015-02-24       Impact factor: 20.543

3.  Comparison of biological characteristics of nucleus pulposus mesenchymal stem cells derived from non-degenerative and degenerative human nucleus pulposus.

Authors:  Zhiwei Jia; Pushan Yang; Yaohong Wu; Yong Tang; Yachao Zhao; Jianhong Wu; Deli Wang; Qing He; Dike Ruan
Journal:  Exp Ther Med       Date:  2017-04-27       Impact factor: 2.447

Review 4.  Cell therapy for the degenerating intervertebral disc.

Authors:  Wei Tong; Zhouyu Lu; Ling Qin; Robert L Mauck; Harvey E Smith; Lachlan J Smith; Neil R Malhotra; Martin F Heyworth; Franklin Caldera; Motomi Enomoto-Iwamoto; Yejia Zhang
Journal:  Transl Res       Date:  2016-11-28       Impact factor: 7.012

Review 5.  Molecular mechanisms of biological aging in intervertebral discs.

Authors:  Nam V Vo; Robert A Hartman; Prashanti R Patil; Makarand V Risbud; Dimitris Kletsas; James C Iatridis; Judith A Hoyland; Christine L Le Maitre; Gwendolyn A Sowa; James D Kang
Journal:  J Orthop Res       Date:  2016-08-12       Impact factor: 3.494

6.  Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene Expression in the Degenerating Rabbit Intervertebral Disk In Vivo.

Authors:  Yejia Zhang; Ana Chee; Peng Shi; Rui Wang; Isaac Moss; Er-Yun Chen; Tong-Chuan He; Howard S An
Journal:  Am J Phys Med Rehabil       Date:  2015-07       Impact factor: 2.159

7.  Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

Authors:  Kathryn T Weber; Timothy D Jacobsen; Robert Maidhof; Justin Virojanapa; Chris Overby; Ona Bloom; Shaheda Quraishi; Mitchell Levine; Nadeen O Chahine
Journal:  Curr Rev Musculoskelet Med       Date:  2015-03

8.  Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc: a novel cell source for disc repair.

Authors:  D Greg Anderson; Dessislava Markova; Howard S An; Ana Chee; Motomi Enomoto-Iwamoto; Vladimir Markov; Biagio Saitta; Peng Shi; Chander Gupta; Yejia Zhang
Journal:  Am J Phys Med Rehabil       Date:  2013-05       Impact factor: 2.159

9.  Biomimetic nucleus pulposus scaffold created from bovine caudal intervertebral disc tissue utilizing an optimal decellularization procedure.

Authors:  Christopher Fernandez; Alan Marionneaux; Sanjitpal Gill; Jeremy Mercuri
Journal:  J Biomed Mater Res A       Date:  2016-08-19       Impact factor: 4.396

10.  Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Authors:  Aubrey T Francisco; Robert J Mancino; Robby D Bowles; Jonathan M Brunger; David M Tainter; Yi-Te Chen; William J Richardson; Farshid Guilak; Lori A Setton
Journal:  Biomaterials       Date:  2013-07-10       Impact factor: 12.479

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