Back/Spine – Disc Pathology – Adipose

Background:

Several cell-based therapies have been proposed in recent years the management of low back pain, including the injection of medicinal signaling cells or mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). However, there is only emerging clinical evidence to support their use at this time.

Purpose:

To assess the effectiveness of MSCs or PRP injections in the treatment of low back and lower extremity pain.

Study Design:

A systematic review and metaanalysis of the effectiveness of PRP and MSCs injections in managing low back and lower extremity pain.

Data Sources:

PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed from 1966 through June 2018.

Study Selection:

Randomized trials, observational studies, and case reports of injections of biologics into the disc, epidural space, facet joints, or sacroiliac joints.

Data Extraction:

Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques – Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques – Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5.

Data Synthesis:

Twenty-one injection studies met inclusion criteria. There were 12 lumbar disc injections, 5 epidural, 3 lumbar facet joint, and 3 sacroiliac joint studies

Results:

Evidence synthesis based on a single-arm metaanalysis, randomized controlled trials (RCTs), and observational studies, disc injections of PRP and MSCs showed Level 3 evidence (on a scale of Level I through V). Evidence for epidural injections based on single-arm metaanalysis, a single randomized controlled trial and other available studies demonstrated Level 4 (on a scale of Level I through V) evidence. Similarly, evidence for lumbar facet joint injections and sacroiliac joint injections without metaanalysis demonstrated Level 4 evidence (on a scale of Level I through V).

Limitations:

Lack of high quality RCTs.

Conclusion:

The findings of this systematic review and single-arm metaanalysis shows that MSCs and PRP may be effective in managing discogenic low back pain, radicular pain, facet joint pain, and sacroiliac joint pain, with variable levels of evidence in favor of these techniques.

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Intervertebral disc (IVD) degeneration is one of the major neurodegenerative diseases throughout the world. Development of new and advanced treatment methods are highly warranted due to the limitations of conventional protocols. Very recently, regenerative medicine techniques based on biomaterials, stem cell and bioactive molecules have been demonstrated as the most powerful concept to regenerate IVD. In this chapter, we will review the recent progress in (1) biomaterial scaffolds for annulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous end plates (CEP), (2) stem cells as cell sources, and finally introduce (3) our recent research studies focusing on the fabrication of natural/synthetic hybrid scaffolds for various purposes during the last 5 years.

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Low back pain with resultant loss of function, decreased productivity, and high economic costs is burdensome for both thevindividual and the society. Evidence suggests that intervertebral disc pathology is a major contributor to spine-related pain and degeneration. When commonly used conservative therapies fail, traditional percutaneous or surgical options may be beneficial for pain relief but are suboptimal because of their inability to alter disc microenvironment catabolism, restore disc tissue, and/or preserve native spine biomechanics. Percutaneously injected Multipotent Mesenchymal Stem Cell (MSC) therapy has recently gained clinical interest for its potential to revolutionarily treat disc-generated (discogenic) pain and associated disc degeneration. Unlike previous therapies to date, MSCs may uniquely offer the ability to improve discogenic pain and provide more sustained improvement by reducing disc microenvironment catabolism and regenerating disc tissue. Consistent treatment success has the potential to create a paradigm shift with regards to the treatment of discogenic pain and disc degeneration.

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Low back pain is a universal and disabling chronic condition that has significantly contributed to rising health care costs. IVD degeneration is the leading cause of back pain and is also often the precursor to the degenerative cascade of facet arthropathy, spinal deformity, and stenosis. Treatments targeting the painful annular fissures early on may also help prevent progression of spinal deformity and disability. Interventions that hinder ongoing cell degradation or that supplement anabolic cell production are necessary cost-effective treatments for low back pain, as the current epidural injection options offer only transient relief and current surgical options cost exorbitantly Regenerative Treatments for Spinal Conditions 1013 more. Surgeries themselves may contribute to adjacent-level degeneration, as seen in spinal fusions.58 Regenerative treatments may also offer a great solution for those refractory to pain management and injections and those who prefer to avoid surgery. The existing translational and clinical studies presented in this article provide supportive evidence for regenerative treatments for discogenic pain, including intradiscal PRP, mesenchymal stem cell, and fibrin treatments. These studies are paving the way to the future of spine medicine, which is shifting toward regenerative biologic treatments and away from spinal fusion surgeries for discogenic low back pain.

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Low back pain is widely recognized as one of the most prevalent pathologies in the developed world. In the United States, low back pain is the most common health problem for adults under the age of 50, resulting in significant societal and personal costs. While the causes of low back pain are myriad, it has been significantly associated with intervertebral disc (IVD) degeneration. Current first-line therapies for IVD degeneration such as physical therapy and spinal fusion address symptoms, but do not treat the underlying degeneration. The use of tissue engineering to treat IVD degeneration provides an opportunity to correct the pathological process. Novel techniques are currently being investigated and have shown mixed results. One major avenue of investigation has been stem cell injections. Mesenchymal stem cells (MSCs) have shown promise in small animal models, but results in larger vertebrates have been mixed.

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Purpose

This review aims to explore and summarize the current clinical evidence about the use of regenerative medicine such as mesenchymal stem cells or platelet-rich plasma in intervertebral disc regeneration, in order to clarify the state of art of these novel approaches.

Materials and methods

We performed a research of the available literature about regenerative medicine strategies aiming to prevent intervertebral disc degeneration. All preclinical trials and in vitro studies were excluded. Only clinical trials were critically analysed.

Results

The manuscript selection produced a total of 7 articles concerning the use of regenerative therapies in intervertebral disc degeneration, covering the period between 2010 and 2016. Articles selected were 4 about the injection of mesenchymal stem cells-related results and 3 using platelet-rich plasma. The total population of patients treated with regenerative medicine strategies were 104 patients.

Conclusions

Regenerative medicine, such as the use of mesenchymal stem cells or platelet-rich plasma, in intradiscal disc degeneration has shown preclinical and clinical positive results. Randomized clinical trials study- ing the potential of MSCs intradiscal injection have not been conducted, and PRP effect has been studied only preliminarily. Additional more powered high-quality studies are needed to really appreciate the long-term safety and efficacy of regenerative medicine approaches in IDD.

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Numerous health care resources are utilized to treat low back pain (LBP) resulting from degenerative disc disease (DDD). Most patients with disc degeneration remain asymptomatic, and the degree of disc degeneration does not correlate with pain severity, making diagnosis and effective treatment challenging.

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Objective:

The objective of this research was to evaluate the influence of autologous mononuclear stem cells injections on histological changes of collagen in the fibrous annulus of the intervertebral disk after experimental injury.

Methods:

32 New Zealand rabbits were submitted to intervertebral disk puncture, followed by intradiscal injection of mononuclear cells from the iliac crest versus saline injection in the following time periods: two months after the injury (SC2M and SS2M), two weeks (SC2W and SS2W) immediately after injury (SCCP and SSCP), and without inducing degeneration (SCSP and SSSP). Two months after cell therapy, the animals were euthanized and collagen changes in the intervertebral discs were histologically evaluated.

Results:

There were significant differences in ELAF between SS2W and SS2S groups (p = 0.018). This difference was due to an increase in type I collagen in SS2W group (56.7%) compared to SC2S (13.28%).

Conclusion:

Treatment with mononuclear mesenchymal stem cells reduced changes in the type I and III collagen distribution in rabbits AF degenerated discs up to two weeks after the induction of degeneration.

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