Biological challenges for regeneration of the degenerated disc using cellular therapies

Bendtsen, Michael; Bünger, Cody; Colombier, Pauline; Visage, Catherine Le; Roberts, Sally; Sakai, Daisuke; Urban, Jill

doi:10.1080/17453674.2017.1297916

Cited by 21 publications

(29 citation statements)

References 62 publications

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“…A recent review of clinical trials by Sakai and Schol reported cell numbers ranging from 1 to 40 million cells being used in investigations . It is postulated that the delivery of large numbers of cells may exacerbate the degenerative microenvironment due to competing nutrient demands, which may in turn result in ineffective clinical outcomes . Given the varying stages of degeneration and microenvironments that exist in vivo, it will be important to tailor or design treatments for individuals.…”

Section: Optimizing Cell Sources and Delivery Techniquesmentioning

confidence: 99%

“…55 It is postulated that the delivery of large numbers of cells may exacerbate the degenerative microenvironment due to competing nutrient demands, which may in turn result in ineffective clinical outcomes. 56 Given the varying stages of degeneration and microenvironments that exist in vivo, it will be important to tailor or design treatments for individuals. One way to achieve this could be to condition stem cells prior to implantation by acclimatizing them to patient specific in vivo microenvironmental milieu, which may include inflammatory cytokines, acidity, oxygen or nutrient deprivation.…”

Section: The Challenges Of the Degenerate Disc Microenvironmentmentioning

confidence: 99%

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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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Section: Optimizing Cell Sources and Delivery Techniquesmentioning

confidence: 99%

Section: The Challenges Of the Degenerate Disc Microenvironmentmentioning

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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“…Hence, discs can only support a limited number of cells before nutrient concentrations in the disc center become too low to maintain cell viability. The cell density supported thus varies inversely with disc height with the cell density in rabbit discs for instance, being 30 to 40 times greater than that in adult human lumbar discs (cell density around 2‐3 × 10 6 cells/mL in a normal human disc).…”

Section: Nomentioning

confidence: 98%

“…Hence, the evidence from randomized controlled trials (RCTs) using appropriate controls is essential before such treatments are routinely adopted. Eight clinical trials using MSCs to treat low back pain have been set up . None have reported any results so far.…”

Section: Nomentioning

confidence: 99%

Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

Loibl¹,

et al. 2019

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Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP. Degeneration is thought to lead to LBP because of nerve ingrowth into the degenerate disc, inflammation, or because degradation of extracellular matrix (ECM) alters spinal biomechanics inappropriately. Thus, while the objectives of some interventions for LBP are to control pain intensity, other interventions aim to deal with the consequences of disc degeneration through stabilizing the disc surgically, by inserting artificial discs or by repairing the disc biologically and preventing progressive IVD degeneration. Despite tremendous research efforts, treatment of LBP through the use of regenerative interventions aiming to repair the IVD is still controversial. The use of mesenchymal stem cells for IVD regeneration in a patient‐based case will be discussed by an ensemble of clinicians and researchers.

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“…Dies beinhaltet biomechanische Alterationen, entzündliche und katabolische Störungen in der Bandscheibe sowie das pathologische Einwachsen von Nerven. Bei fortgeschrittenen degenerativen Veränderungen erschweren zudem eine nutritive Deprivation und andere schwierige lokale Verhältnisse regenerative Therapiebemühungen [16].…”

Section: Kurative Und Präventive Behandlungskonzepteunclassified

Bandscheibenregeneration – Konzepte und Ergebnisse

Hegewald¹

2019

Die Wirbelsäule

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Biological challenges for regeneration of the degenerated disc using cellular therapies

Cited by 21 publications

References 62 publications

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

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

Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

Bandscheibenregeneration – Konzepte und Ergebnisse

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