Intradiscal Mesenchymal Stromal Cell Therapy for the Treatment of Low Back Pain Due to Moderate-to-Advanced Multilevel Disc Degeneration: A Preliminary Report of a Double-Blind, Phase IIB Randomized Clinical Trial (DREAM Study)

Gianluca Vadalà; Fabrizio Russo; Cristiana Lavazza; Giorgia Petrucci; Luca Ambrosio; Silvia Budelli; Elisa Montelatici; Giuseppina Di Giacomo; Claudia Cicione; Veronica Tilotta; Giuseppe Francesco Papalia; Matteo Pileri; Amalia Bruno; Salvatore La Rosa; Emilio Carrino; Eliodoro Faiella; Massimiliano Carassiti; Lorenza Lazzari; Rocco Papalia; Vincenzo Denaro

doi:10.1002/jsp2.70086

Intradiscal Mesenchymal Stromal Cell Therapy for the Treatment of Low Back Pain Due to Moderate-to-Advanced Multilevel Disc Degeneration: A Preliminary Report of a Double-Blind, Phase IIB Randomized Clinical Trial (DREAM Study)

JOR Spine. 2025 Jun 2;8(2):e70086. doi: 10.1002/jsp2.70086. eCollection 2025 Jun.

Authors

Gianluca Vadalà^{1

2}, Fabrizio Russo^{1

2}, Cristiana Lavazza³, Giorgia Petrucci¹, Luca Ambrosio^{1

2}, Silvia Budelli³, Elisa Montelatici³, Giuseppina Di Giacomo², Claudia Cicione², Veronica Tilotta², Giuseppe Francesco Papalia^{1

2}, Matteo Pileri^{4

5}, Amalia Bruno^{4

5}, Salvatore La Rosa³, Emilio Carrino³, Eliodoro Faiella^{4

5}, Massimiliano Carassiti^{6

7}, Lorenza Lazzari³, Rocco Papalia^{1

2}, Vincenzo Denaro¹

Affiliations

¹ Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio-Medico Rome Italy.
² Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery Department of Medicine and Surgery, Università Campus Bio-Medico di Roma Rome Italy.
³ Unit of Cell and Gene Therapies Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milano Milan Italy.
⁴ Operative Research Unit of Radiology and Interventional Radiology Fondazione Policlinico Universitario Campus Bio-Medico Rome Italy.
⁵ Research Unit of Radiology Department of Medicine and Surgery, Università Campus Bio-Medico di Roma Rome Italy.
⁶ Operative Research Unit of Anesthesia and Intensive Care Fondazione Policlinico Universitario Campus Bio-Medico Rome Italy.
⁷ Research Unit of Anaesthesia and Intensive Care Department of Medicine and Surgery, Università Campus Bio-Medico di Roma Rome Italy.

Abstract

Background: Low back pain (LBP) is a leading cause of disability worldwide, often associated with intervertebral disc degeneration (IDD). Mesenchymal stromal cells (MSCs) have emerged as a promising regenerative therapy for IDD due to their ability to promote tissue repair. This phase IIB randomized controlled trial aimed to evaluate the safety and efficacy of autologous bone marrow-derived MSC (BM-MSC) intradiscal injections in patients with chronic LBP due to moderate-to-advanced multilevel IDD.

Methods: Fifty-two patients with chronic LBP unresponsive to conservative treatments with moderate-to-advanced IDD at up to three lumbar levels were included. Participants were randomized to receive either BM-MSCs or a sham procedure. Clinical outcomes, including pain intensity (VAS), disability (ODI), and quality of life (SF-36), were assessed at baseline, 1-, 3-, and 6-months postinjection. Structural changes were evaluated via MRI using Pfirrmann grading, disc height index (DHI), and T2 mapping at baseline, 3 and 6 months.

Results: Of the 52 enrolled patients, 46 completed the 6-month follow-up (BM-MSC group: n = 21; sham group: n = 25). BM-MSC injections were well-tolerated, with no major adverse events reported. Structural improvements were observed in the BM-MSC group, including significant increases in DHI and nonsignificant improvements in T2 relaxation times at 3 and 6 months. Modified Pfirrmann grades showed transient improvement at 3 months but returned to baseline at 6 months. Despite these radiological changes, clinical outcomes such as VAS, ODI, and SF-36 scores improved similarly in both groups without significant intergroup differences at any timepoint. The sham group demonstrated slightly greater improvements in disability (ODI) and physical quality-of-life scores (SF-36 PCS).

Conclusions: Autologous BM-MSC intradiscal injection is a safe and promising approach in patients with chronic LBP due to moderate-to-advanced multilevel IDD. However, despite these regenerative effects, no significant clinical advantages over the sham procedure were observed within 6 months of follow-up.

Keywords: RCT; clinical trial; intervertebral disc degeneration; intervertebral disc regeneration; low back pain; regenerative medicine; stem cells.