Degenerative disc disease (DDD) induces chronic back pain with limited nonsurgical options. In this open label pilot study, 26 patients (median age 40 years; range 18-61) received autologous bone marrow concentrate (BMC) disc injections (13 one level, 13 two levels). Pretreatment Oswestry disability index (ODI) and visual analog scale (VAS) were performed to establish baseline pain scores (average 56.5 and 79.3, respectively), while magnetic resonance imaging was independently scored according to the modified Pfirrmann scale. Approximately 1 ml of BMC was analyzed for total nucleated cell (TNC) content, colony-forming unit-fibroblast (CFU-F) frequency, differentiation potential, and phenotype characterization. The average ODI and VAS scores were reduced to 22.8 and 29.2 at 3 months, 24.4 and 26.3 at 6 months, and 25.0 and 33.2 at 12 months, respectively (p .0001). Eight of twenty patients improved by one modified Pfirrmann grade at 1 year. The average BMC contained 121 3 10 6 TNC/ml with 2,713 CFU-F/ml (synonymous with mesenchymal stem cells). Although all subjects presented a substantial reduction in pain, patients receiving greater than 2,000 CFU-F/ml experienced a significantly faster and greater reduction in ODI and VAS. Subjects older than 40 years who received fewer than 2,000 CFU-F/ml experienced an average pain reduction of 33.7% (ODI) and 29.1% (VAS) at 12 months, while all other patients' average reduction was 69.5% (ODI, p 5 .03) and 70.6% (VAS, p 5 .01). This study provides evidence of safety and feasibility in the nonsurgical treatment of DDD with autologous BMC and indicates an effect of mesenchymal cell concentration on discogenic pain reduction. STEM CELLS 2015;33:146-156

There were no adverse events related to marrow aspiration or injection, and this study provides evidence of safety and feasibility of intradiscal BMC therapy. Patient improvement and satisfaction with this surgical alternative supports further study of the therapy.

This study provides evidence of safety and feasibility in the non-surgical treatment of discogenic pain with autologous BMC, with durable pain relief (71 % VAS reduction) and ODI improvements (> 64 %) through two years.

Titanium is a successful biomaterial that possesses good biocompatibility. It is covered by a surface layer of titanium dioxide, and this oxide may play a critical role in inhibiting reactive oxygen species, such as peroxynitrite, produced during the inflammatory response. In the present study, titanium dioxide was coated onto silicone substrates by radio-frequency sputtering. Silicone coating with titanium dioxide enhanced the breakdown of peroxynitrite by 79%. At physiologic pH, the peroxynitrite donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) was used to nitrate 4-hydroxyphenylacetic acid (4-HPA) to form 4-hydroxy-3-nitrophenyl acetic acid (NHPA). Titanium dioxide-coated silicone inhibited the nitration of 4-HPA by 61% compared to aluminum oxide-coated silicone and 55% compared to uncoated silicone. J774A.1 mouse macrophages were plated on oxide-coated silicone and polystyrene and stimulated to produce superoxide and interleukin-6. Superoxide production was measured by the chemiluminescent reaction with 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (MCLA). Titanium dioxide-coated silicone exhibited a 55% decrease in superoxide compared to uncoated silicone and a 165% decrease in superoxide compared to uncoated polystyrene. Titanium dioxide-coated silicone inhibited IL-6 production by 77% compared to uncoated silicone. These results show that the anti-inflammatory properties of titanium dioxide can be transferred to the surfaces of silicone substrates.