3. Discussion
LBP, discogenic LBP, stenosis, pain
DEGENERATIVE SPONDYLOLISTHESIS, DEGENERATED, KNEE OSTEOARTHRITIS, LEAKAGE, STENOSIS
The range of image-guided percutaneous interventional techniques developed for the treatment of discogenic LBP emphasizes minimal invasiveness and maximal pain relief. These procedures, which include radiofrequency annuloplasty, intradiscal electrothermal therapy, and chemonucleolysis with agents like medical ozone, operate through distinct mechanisms. However, the evidence from various studies remains inconclusive regarding their effectiveness. The ongoing debate highlights the need for more definitive research to establish the safety and efficacy of stem cell therapy and its potential to be preferred alternatives to percutaneous interventional techniques [What sets our clinical trial apart is the use of matrilin-3 protein to enhance MSC functionality before processing them into spheroids for administration. Matrilin-3 plays a crucial role in the development of cartilage and ossification, and as well as interacting with essential growth factors [Our in vitro studies revealed that a 5-day priming with 10 ng/mL of matrilin-3 led to maximum mRNA expression of type 2 collagen and aggrecan [Although the exact mechanism of improvement remains elusive, our previous studies hint that matrilin-3-primed ASC spheroids could effectively restore ECM in degenerated disc, with benefits attributed to spheroid formation and matrilin-3 priming [In our study, we examined reasons for treatment failures in cases 1 and 6. Case 1 showed a significant drop in CD44 positivity (87.2%), potentially affecting the efficacy of the matrilin-3-primed ASC spheroids, while maintaining high CD73 positivity (97.9%). In contrast, case 6, despite having full CD44 positivity (100%), displayed decreased CD73 positivity (87.4%) and presented radiological signs of degenerative spondylolisthesis and spinal stenosis. These factors might have influenced the treatment’s ineffectiveness (Our study aligns with previous clinical trials [As we extend our research, our phase 2 clinical trial will aim to build upon these initial findings. In this next phase, we intend to introduce a control group and enlarge our participant pool, enhancing the statistical robustness of our results. Additionally, we plan to extend the follow-up duration to more effectively assess the long-term efficacy of matrilin-3-primed ASC spheroids.Our study acknowledges multiple limitations: a limited sample size, the lack of a control group, and a brief 6-month follow-up period. While discography might precisely pinpoint the disc causing chronic LBP, our selection for cell injection was based on clinical observations, MRI findings, and pain block procedures. This choice brings into question the exactness in identifying the chronic LBP source. The HA, used alongside the ASC spheroid implantation to prevent cell leakage, was originally designed for knee osteoarthritis, not for disc interventions. Given these limitations and the acknowledgment that additional comprehensive research is needed, it’s prudent to be cautious when drawing definitive conclusions regarding the long-term safety and efficacy of the treatment. Nevertheless, our initial findings point to the safety and potential therapeutic value of our approach.