1. 2024;27;E995-E1032Effectiveness of Intradiscal Regenerative Medicine Therapies for Long-Term Relief of Chronic Low Back Pain: A Systematic Review and Meta-Analysis
   Systematic Review
   Laxmaiah Manchikanti, MD, Emilija Knezevic, ., Nebojsa Nick Knezevic, MD, PhD, Alan D. Kaye, MD, PhD, Sairam Atluri, MD, Mahendra R. Sanapati, MD, Vidyasagar Pampati, MSc, and Joshua A. Hirsch, MD.

BACKGROUND: Recent research underscores the potential of intradiscal biologics, such as mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and alpha-2-macroglobulin, in promoting chondrogenesis within lumbar intervertebral discs as a treatment for discogenic low back pain. Studies indicate significant improvements in pain relief, physical function, and overall quality of life following these interventions.

OBJECTIVE: This study aims to evaluate the effectiveness of intradiscal injections of MSCs and PRP in managing low back and lower extremity pain. A systematic review and meta-analysis were conducted to assess the outcomes of these treatments.

STUDY DESIGN: A systematic review and meta-analysis evaluating the efficacy of PRP and MSC injections for discogenic low back and lower extremity pain.

DATA SOURCES: The review included literature from PubMed, Cochrane Library, the U.S. National Guideline Clearinghouse (NGC), prior systematic reviews, and reference lists, covering studies from 1966 to September 2024.

STUDY SELECTION: Randomized controlled trials (RCTs), observational studies, and case reports focusing on biologic injections into the disc were included.

DATA EXTRACTION AND SYNTHESIS: Data were extracted and assessed for methodological quality. Evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and summarized based on best evidence synthesis principles on a 1-to-5 scale.

RESULTS: The analysis included 8 RCTs (4 evaluating PRP, 5 evaluating MSCs) and 8 observational studies (4 assessing PRP, 4 assessing MSCs) for managing chronic low back pain. Evidence quality was deemed fair (Level III) with limited certainty and moderate recommendation strength based on qualitative and quantitative analyses.

LIMITATIONS: Paucity of high-quality studies.

CONCLUSION: This systematic review and single-arm meta-analysis suggest that intradiscal injections of MSCs and PRP may be effective in managing discogenic low back pain, supported by Level III evidence.

KEY WORDS: Chronic low back pain, discogenic pain, regenerative therapy, mesenchymal stem cells, platelet-rich plasma, intradiscal injection