Disc Regeneration Therapy Using Marrow Mesenchymal Cell Transplantation

Yoshikawa, Takafumi; Ueda, Yuichiro; Miyazaki, Kiyoshi; Koizumi, Munehisa; Takakura, Yoshinori

doi:10.1097/brs.0b013e3181cd2cf4

Cited by 225 publications

(212 citation statements)

References 47 publications

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“…In clinical studies, injection of autologous bone marrow MSCs into nucleous pulposus improved pain and disability and water content was increased; albeit, disc height was not restored at 12-months postinjection (96). Similar outcomes were found in a different study where two patients with disc degeneration experienced pain relief and increase in water content of the disc at 2 years after injection of autologous MSCs (97). In another study, 10 patients who underwent intradiscal injection of hematopoietic precursor stem cells obtained from their pelvic bone marrow experienced no clinical improvement of their discogenic low back pain after 1 year (98).…”

Section: Cell Replacementsupporting

confidence: 60%

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Vasiliadis

Pneumaticos

Evangelopoulos

et al. 2014

Mol Med

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Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Proteinbased therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration.

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Section: Cell Replacementsupporting

confidence: 60%

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Vasiliadis

Pneumaticos

Evangelopoulos

et al. 2014

Mol Med

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“…8,17,47 The encouraging results obtained using MSCs in experimental animal models 11,19,20,40,41,43,51 have been followed by a recent human clinical study in which autologous bone marrow-derived MSCs were used to reconstitute degenerate discs. 49 The MSCs were added to collagen sponges and implanted into the excised NP space of symptomatic degenerate discs of 2 older women (ages 67 and 70) with low-back pain. Twenty-four months later, clinical assessment revealed that these 2 patients had obtained symptomatic improvement and greater spinal stability accompanied by enhanced T2-weighted MRI signal in the MSC-injected discs.…”

mentioning

confidence: 99%

Immunoselected STRO-3+mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs

Ghosh

Moore

Vernon‐Roberts

et al. 2012

SPI

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ObjectChronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model.MethodsThree adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3–4 discs of all animals were injected with either a high dose (4 × 106cells, in 12 sheep) or low dose (0.5 × 106cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4–5 degenerate discs remained untreated; the L5–6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment).ResultsInjection of cABC decreased the disc height index (DHI) of target discs by 45%–50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC–injected discs and at 6 months posttreatment for the low-dose MPC–injected discs were significantly different from those of the noninjected and HA-injected discs (p <0.001) but not from the control disc scores.ConclusionsOn the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.

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Section: Intervertebral Discmentioning

confidence: 99%

“…Yoshikawa et al [51] reported two cases of autologous MSC implantation in markedly degenerate intervertebral discs. Symptomatic and radiological improvement was demonstrated without significant adverse effects [51] . A larger series of 10 patients treated with autologous MSCs demonstrated improvement in pain, disability and disc hydration [52] .…”

Section: Intervertebral Discmentioning

confidence: 99%

Mesenchymal stem cell tracking in the intervertebral disc

Handley

Goldschlager

Oehme

et al. 2015

WJSC

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Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc (IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management, including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD.

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Disc Regeneration Therapy Using Marrow Mesenchymal Cell Transplantation

Abstract: The intervertebral disc regeneration therapy using MSC brought about favorable results in these 2 cases. It seems to be a promising minimally invasive treatment.

Cited by 225 publications

References 47 publications

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Immunoselected STRO-3+mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs

Mesenchymal stem cell tracking in the intervertebral disc

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