Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells

Noriega, David C.; Ardura, Francisco; Hernández-Ramajo, Rubén; Martín-Ferrero, Miguel Ángel; Sánchez-Lite, Israel; Toribio, Borja; Alberca, Mercedes; García, Verónica; Moraleda, José Marı́a; Sánchez, Abraham; García‐Sancho, Javier

doi:10.1097/tp.0000000000001484

Cited by 193 publications

(294 citation statements)

References 46 publications

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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: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…Stem cell therapies have received considerable attention due to their versatility, translatability and potential for long term native tissue regeneration. Some successful patient outcomes have been demonstrated in clinical studies using this approach . The bone marrow has been the prime site of MSC isolation for disc regeneration applications, inclusive of in vitro, preclinical and clinical studies .…”

Section: Optimizing Cell Sources and Delivery Techniquesmentioning

confidence: 99%

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

et al. 2018

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Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials.

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“…In a recent controlled study of 24 patients with chronic low back pain, 12 received a transplantation of allogeneic mesenchymal bone marrow cells via intradiscal injection (Noriega et al, 2016). Five of the treated patients (~40%) displayed a quick and significant improvement in pain relief suggesting that this simple, non-surgical procedure can provide pain relief to a certain percentage of those suffering from chronic low back pain (Noriega et al, 2016).…”

Section: Stem Cells In Human Clinical Trials For Ivd Diseasementioning

confidence: 99%

“…Five of the treated patients (~40%) displayed a quick and significant improvement in pain relief suggesting that this simple, non-surgical procedure can provide pain relief to a certain percentage of those suffering from chronic low back pain (Noriega et al, 2016). In another recent independent study on humans (Elabd et al, 2016), five patients who presented with degenerated discs had bone marrow mesenchymal stem cells removed and cultured in vitro under hypoxic conditions, which is the normal state of the IVD.…”

Section: Stem Cells In Human Clinical Trials For Ivd Diseasementioning

confidence: 99%

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

Kraus

Lufkin

2017

Front. Cell Dev. Biol.

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The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 1013 cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones. One area receiving attention is regeneration of the intervertebral discs (IVDs), which are located between the vertebrae and function to give flexibility and support load to the spine. Degenerated discs are a major cause of lower back pain. Different stem cell based regenerative medicine approaches to cure disc degeneration are now available, including using autologous mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs) and even attempts at direct transdifferentiation of somatic cells. Here we discuss some of the recent advances, successes, drawbacks, and the failures of the above-mentioned approaches.

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Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells

Abstract: Allogeneic MSC therapy may be a valid alternative for the treatment of degenerative disc disease that is more logistically convenient than the autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves disc quality.

Cited by 193 publications

References 46 publications

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

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

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

Implications for a Stem Cell Regenerative Medicine Based Approach to Human Intervertebral Disk Degeneration

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