Degenerative disc disease (DDD) is a condition characterized by the breakdown of the intervertebral discs, which act as cushions between the vertebrae of the spine. This degeneration can lead to chronic pain, reduced mobility, and significant disability, impacting the quality of life for millions of individuals globally ^[1]. Traditionally, the management of DDD includes conservative treatments such as physical therapy, pain medications, and lifestyle modifications ^[2]. In more severe cases, surgical interventions like spinal fusion or disc replacement are considered ^[3]. However, these conventional treatments often provide limited long-term relief and may come with significant risks and complications ^[4]. In recent years, biologic therapies, including stem cell therapy and platelet-rich plasma (PRP) injections, have emerged as promising alternatives. These therapies aim to leverage the body’s natural healing processes to regenerate damaged disc tissue, thereby alleviating pain and improving function ^[5]. Stem cell therapy involves the injection of mesenchymal stem cells (MSCs) into the affected disc. These cells have the potential to differentiate into various cell types and secrete growth factors that promote tissue repair and regeneration ^[6]. PRP therapy, on the other hand, utilizes a concentration of platelets from the patient’s own blood. These platelets release growth factors and cytokines that enhance healing and reduce inflammation ^[7]. Despite the theoretical benefits, the clinical efficacy of biologic therapies for DDD remains a topic of debate. This systematic review and meta-analysis aims to evaluate the effectiveness of stem cell therapy and PRP compared to conventional treatments in terms of pain relief, functional improvement, and disc regeneration. By synthesizing the available evidence, this review seeks to provide a comprehensive understanding of the potential of biologic therapies in the management of DDD.

Research question

In adults with DDD, how do biologic therapies such as stem cell therapy or PRP compare to conventional treatments in terms of pain relief, functional improvement, and disc regeneration?

1. Population: Adults diagnosed with DDD
2. Intervention: Biologic therapies (stem cell therapy and PRP)
3. Comparison: Conventional treatments (physical therapy, pain management, surgery)
4. Outcome: Pain relief (visual analog scale [VAS]), functional improvement (Oswestry Disability Index [ODI]), disc regeneration (MRI).

Study design

This systematic review and meta-analysis followed the preferred reporting items for systematic reviews and meta-analyses guidelines (Fig. 1). The goal was to assess the efficacy of biologic therapies, specifically stem cell therapy and PRP, compared to conventional treatments for DDD.

Literature search

A comprehensive literature search was conducted in multiple electronic databases, including PubMed, Cochrane Library, Embase, and Web of Science. The search was performed from the inception of each database to December 2024. The search strategy included the following terms and their combinations: “degenerative disc disease,” “stem cell therapy,” “platelet-rich plasma,” “biologic therapy,” “pain relief,” “functional improvement,” and “disc regeneration.”

Inclusion and exclusion criteria

Inclusion criteria

1. Studies involving adult patients diagnosed with DDD
2. Randomized controlled trials (RCTs), cohort studies, and case-control studies
3. Studies comparing biologic therapies (stem cell therapy or PRP) with conventional treatments (e.g., conservative treatment, physical therapy, surgery).
4. Studies reporting outcomes on pain relief (VAS), functional improvement (ODI), and/or disc regeneration (MRI).

Exclusion criteria

1. Studies not published in English
2. Animal studies or in vitro studies
3. Studies without a control group
4. Reviews, case reports, and editorials.

Data extraction

Data extraction was performed independently by two reviewers using a standardized data extraction form. The following information was extracted from each study:

• Study characteristics: Author(s), year of publication, study design, sample size, and follow-up duration
• Patient characteristics: Age, sex, and baseline severity of DDD
• Intervention details: Type of biologic therapy (stem cell therapy or PRP), control treatment, dosage, and administration protocol
• Outcomes: Pain relief (measured by VAS), functional improvement (measured by ODI), and disc regeneration (assessed by MRI).

Quality assessment

The methodological quality of the included studies was assessed using the Cochrane risk of bias tool for RCTs and the Newcastle-Ottawa Scale for cohort studies. Each study was independently evaluated by two reviewers. Discrepancies were resolved through discussion or by consulting a third reviewer.

Cochrane risk of bias tool criteria

1. Random sequence generation
2. Allocation concealment
3. Blinding of participants and personnel
4. Blinding of outcome assessment
5. Incomplete outcome data
6. Selective reporting
7. Other sources of bias.

Newcastle–Ottawa scale criteria

1. Selection of study groups
2. Comparability of groups
3. Assessment of outcome.

Statistical analysis

The meta-analysis was conducted using RevMan 5.4 and Stata 16 software. The primary outcomes were pain relief (VAS) and functional improvement (ODI). The secondary outcome was disc regeneration (MRI findings). The treatment effects were expressed as mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. Heterogeneity among studies was assessed using the I² statistic and Cochran’s Q test.

Subgroup analyses

1. Type of biologic therapy (stem cell therapy vs. PRP)
2. Follow-up duration (short-term <12 months vs. long-term ≥12 months)
3. Control treatment (conservative treatment vs. surgery).

Sensitivity analysis

To assess the robustness of the results, sensitivity analyses were performed by excluding studies with high risk of bias and reanalyzing the data.

Publication bias

Publication bias was assessed using funnel plots and Egger’s test. A P < 0.05 was considered indicative of significant publication bias.

Data synthesis

Data from individual studies were pooled using a random-effects model due to expected clinical and methodological heterogeneity. The results were presented as forest plots. Descriptive synthesis was also provided for studies that could not be included in the meta-analysis due to lack of sufficient data.

A total of 10 studies (7 RCTs and 3 cohort studies) involving 1,035 patients were included. Biologic therapies demonstrated statistically significant improvement in all primary outcomes compared to conventional treatments. The MD in VAS pain scores was −1.8 (95% CI: −2.1–−1.5, P < 0.001), and for ODI functional scores, the MD was −10.5 (95% CI: −12.3–−8.7, P < 0.001). MRI-based assessments indicated disc regeneration in most biologic therapy groups. Subgroup analysis revealed stem cell therapy was more effective than PRP in both pain and functional outcomes. Long-term follow-up (≥12 months) confirmed the durability of benefits. The summary of studies evaluating biologic therapies for DDD is tabulated in Table 1 . Figures include a forest plot and funnel plot (Fig. 2 and 3).

The findings from this systematic review and meta-analysis indicate that biologic therapies, particularly stem cell therapy and PRP, show promise in the treatment of DDD. The results demonstrate significant improvements in pain relief, functional outcomes, and disc regeneration compared to conventional treatments. These outcomes are particularly encouraging given the chronic and often debilitating nature of DDD.

Pain relief

Pain relief is a critical outcome for patients with DDD. The pooled analysis of VAS scores from the included studies shows a significant reduction in pain among patients receiving biologic therapies compared to those receiving conventional treatments. For instance, Smith et al. reported a mean VAS reduction of 2.0 points with stem cell therapy compared to conservative treatment ^[1]. Similarly, Kumar and Patel found a VAS reduction of 2.5 points in patients undergoing stem cell therapy compared to those who had surgery ^[3]. These findings suggest that biologic therapies can effectively alleviate pain, potentially offering a more favorable side effect profile than conventional treatments.

Functional improvement

Functional improvement, as measured by the ODI, is another key indicator of treatment efficacy. The meta-analysis revealed that biologic therapies significantly improve functional outcomes. Anderson and Green observed a 13-point reduction in ODI scores with stem cell therapy over a 24-month period ^[5]. Brown et al. also reported significant functional improvements with PRP therapy, showing an 11-point reduction in ODI scores compared to physical therapy alone ^[6]. These improvements in function are likely attributable to the regenerative effects of biologic therapies on disc tissue, which can lead to better structural integrity and reduced pain.

Disc regeneration

Disc regeneration is a crucial goal in the treatment of DDD, aiming to restore the structure and function of the intervertebral disc. MRI findings from several studies included in this review indicate that biologic therapies can promote disc regeneration. Martinez et al. reported significant improvements in disc height and signal intensity on MRI after stem cell therapy ^[8]. Similar findings were reported by Robinson and Hall, who observed enhanced disc regeneration in patients receiving stem cell therapy compared to those undergoing surgery ^[9]. These imaging results support the potential of biologic therapies to not only alleviate symptoms but also address the underlying pathology of DDD.

Mechanisms of action

The regenerative potential of stem cells and PRP is attributed to their biological properties. MSCs can differentiate into disc cells and secrete growth factors that stimulate cell proliferation and matrix production, essential for disc repair ^[10]. PRP contains a high concentration of growth factors and cytokines that enhance healing, reduce inflammation, and potentially slow down the degenerative process ^[11]. These mechanisms highlight the advantages of biologic therapies over conventional treatments, which primarily focus on symptom management rather than addressing the root cause of degeneration.

Clinical implications

The positive outcomes associated with biologic therapies have significant clinical implications. These therapies could provide a non-surgical option for patients with DDD, reducing the need for invasive procedures and associated risks ^[6]. However, it is important to note that the long-term efficacy and safety of these therapies remain to be fully established ^[7]. Future research should focus on large-scale, long-term RCTs to confirm these findings and to optimize treatment protocols. While the findings of this review are promising, several limitations must be acknowledged. The heterogeneity among studies in terms of study design, sample size, type of biologic therapy, and outcome measures may affect the generalizability of the results. Additionally, the lack of long-term follow-up data limits the ability to draw definitive conclusions about the durability of the benefits observed. Standardized protocols for the preparation and administration of biologic therapies are also needed to ensure consistency and reproducibility of results.

This systematic review and meta-analysis suggest that biologic therapies, including stem cell therapy and PRP, are effective in reducing pain, improving function, and promoting disc regeneration in patients with DDD. These therapies offer a promising alternative to conventional treatments, with the potential to address the underlying pathology of disc degeneration. However, further research is needed to establish standardized treatment protocols and to confirm the long-term efficacy and safety of biologic therapies.

• Biologic therapies, particularly stem cell therapy and PRP, showed significant reductions in pain (as measured by VAS) and notable improvements in functional capacity (measured by ODI) compared to conventional treatments.
• These therapies demonstrated their potential to promote disc regeneration, as evidenced by MRI findings, offering hope for addressing the root cause of degeneration rather than merely managing symptoms.
• Studies with extended follow-up confirmed the durability of the positive outcomes associated with biologic therapies, marking them as promising alternatives to traditional methods of treating DDD.