BackgroundDegenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management, which vary in the rate of success and also carry an increased risk of morbidity and mortality associated with the procedures. Several animal based studies and a few human pilot studies have demonstrated safety and suggest efficacy in the treatment of DDD with mesenchymal stem cells (MSCs). The use of bone marrow-derived MSCs for the treatment of DDD is promising and in the present study we report on the safety and efficacy findings from a registry based proof of concept study using a percutaneous intradiscal injection of cultured MSCs for the management of DDD with associated radicular symptoms.MethodsThirty-three patients with lower back pain and disc degeneration with a posterior disc bulge diagnosed on magnetic resonance imaging (MRI) met the inclusion criteria and were treated with culture-expanded, autologous, bone marrow-derived MSCs. Prospective registry data was obtained at multiple time intervals up to 6 years post-treatment. Collected outcomes included numeric pain score (NPS), a modified single assessment numeric evaluation (SANE) rating, functional rating index (FRI), measurement of the intervertebral disc posterior dimension, and adverse events.ResultsThree patients reported pain related to procedure that resolved. There were no serious adverse events (i.e. death, infection, or tumor) associated with the procedure. NPS change scores relative to baseline were significant at 3, 36, 48, 60, and 72 months post-treatment. The average modified SANE ratings showed a mean improvement of 60% at 3 years post-treatment. FRI post-treatment change score averages exceeded the minimal clinically important difference at all time points except 12 months. Twenty of the patients treated underwent post-treatment MRI and 85% had a reduction in disc bulge size, with an average reduction size of 23% post-treatment.ConclusionsPatients treated with autologous cultured MSCs for lower back pain with radicular symptoms in the setting of DDD reported minor adverse events and significant improvements in pain, function, and overall subjective improvement through 6 years of follow-up.NCT03011398. A Clinical Registry of Orthobiologics Procedures. https://clinicaltrials.gov/ct2/show/NCT03011398?term=orthobiologics&rank=1

BackgroundEpidural steroid injections (ESI) are the most common pain management procedure performed in the US, however evidence of efficacy is limited. In addition, there is early evidence that the high dose of corticosteroids used can have systemic side effects. We describe the results of a case series evaluating the use of platelet lysate (PL) epidural injections for the treatment of lumbar radicular pain as an alternative to corticosteroids.MethodsRegistry data was obtained for patients (N = 470) treated with PL epidural injections presenting with symptoms of lumbar radicular pain and MRI findings that were consistent with symptoms. Collected outcomes included numeric pain score (NPS), functional rating index (FRI), and a modified single assessment numeric evaluation (SANE) rating.ResultsPatients treated with PL epidurals reported significantly lower (p < .0001) NPS and FRI change scores at all time points compared to baseline. Post-treatment FRI change score means exceeded the minimal clinically important difference beyond 1 month. Average modified SANE ratings showed 49.7% improvement at 24 months post-treatment. Twenty-nine (6.3%) patients reported mild adverse events related to treatment.ConclusionPatients treated with PL epidurals reported significant improvements in pain, exceeded the minimal clinically important difference (MCID) for FRI, and reported subjective improvement through 2-year follow-up. PL may be a promising substitute for corticosteroid.

BackgroundCell-based therapies have shown promise for the treatment of knee osteoarthritis (OA). The current study compared exercise therapy to autologous bone marrow concentrate (BMC) and platelet products for knee OA treatment.MethodsPatients with symptomatic knee OA (N = 48) were randomized into either an exercise therapy control group or treatment group with injection of autologous BMC and platelet products. Patients in the control group could crossover to BMC treatment after 3 months. Clinical outcomes were documented at baseline and at 6-weeks, 3, 6, 12 and 24 months, including the Knee Society Score (KSS), Pain Visual Analogue Scale, Short Form-12 Scales (SF-12), and Lower Extremity Activity Scale (LEAS).ResultsAll patients in the exercise group crossed over to receive BMC treatment after 3 months (N = 22 crossover). At 3 months, KSS-knee, SF-12 Physical, and LEAS improved significantly in the crossover group compared to exercise, similar to significant improvements on KSS-knee and LEAS for the treatment group (N = 26) compared to exercise group at 3 months. After BMC treatment, patients’ clinical outcome scores (except SF-12 Mental Health), were significantly improved through the 2-year follow-up compared to baseline. No serious adverse events were reported.ConclusionThe use of image-guided percutaneous BMC with platelet products yielded better results than exercise therapy as an effective alternative therapy for patients with symptomatic moderate to moderate-severe osteoarthritis of the knee.Trial registration NCT02034032. https://clinicaltrials.gov/ct2/show/NCT02034032. Registered 13 January 2014

Injectable regenerative therapies such as bone marrow concentrate (BMC) and platelet-rich plasma (PRP) may represent a safe alternative in the treatment of rotator cuff tears. This is a midterm review of a randomized, crossover trial comparing autologous BMC and platelet product injections versus exercise therapy in the treatment of partial and full-thickness supraspinatus tears. Patients enrolled into the study were between 18 and 65 years of age presenting to an outpatient orthopedic clinic with partial to full thickness, nonretracted supraspinatus tendon tears. Enrolled patients were randomized to either ultrasound-guided autologous BMC with PRP and platelet lysate (PL) percutaneous injection treatment or exercise therapy. Patients could cross over to BMC treatment after at least 3 months of exercise therapy. Patients completed the Disability of the Arm, Shoulder and Hand (DASH) scores as the primary outcome measure. Secondary outcomes included the numeric pain scale (NPS), a modified Single Assessment Numeric Evaluation (SANE), and a blinded MRI review. At this midterm review, results from 25 enrolled patients who have reached at least 12-month follow-up are presented. No serious adverse events were reported. Significant differences were seen in patient reported outcomes for the BMC treatment compared to exercise therapy at 3 and 6 months for pain, and for function and reported improvement (SANE) at 3 months (p<.05). Patients reported a mean 89% improvement at 24 months, with sustained functional gains and pain reduction. MRI review showed a size decrease of most tears post-BMC treatment. These findings suggest that ultrasound-guided BMC and platelet product injections are a safe and useful alternative to conservative exercise therapy of torn, nonretracted supraspinatus tendons. This trial is registered with NCT01788683.

BackgroundBone marrow concentrate (BMC) has shown promise in the treatment of several orthopedic conditions. This registry study investigated the use of autologous BMC and platelet products for percutaneous anterior cruciate ligament (ACL) treatment.MethodsTwenty-nine patients presenting to a single outpatient interventional musculoskeletal and pain practice with symptomatic grade 1, 2, or 3 ACL tears with less than 1 cm retraction were enrolled. Patients were treated with a percutaneous ACL injection of autologous BMC and platelet products using fluoroscopic guidance. Pre- and post-treatment magnetic resonance imaging analysis was completed for 23 patients using ImageJ software for an objective quantitative analysis of pixel density as a proxy for ACL integrity. Subjective clinical outcome measures collected pre-treatment and at 1, 3, 6, 12, 18, 24, and 36 months post-treatment include the Numerical Pain Scale (NPS), the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) form, and a modified version of the Single Assessment Numeric Evaluation.ResultsSeventy-seven percent of patients treated with BMC injections into the ACL showed significant improvement (p < 0.01) in objective measures of ACL integrity at an average of 8.8 months (median 4.7 months). The mean of last patient-reported improvement was 72% (SD = 35) at an average of 23 (SD = 10) months post-treatment. Mean scores were found to be significantly different (p < 0.05) for the NPS at 6, 18, and 24 months, and LEFS and IKDC at all time points (i.e. 1, 3, 6, 12, 18, 24, and 36 months) relative to baseline.ConclusionIn symptomatic patients with grade 1, 2, or even grade 3 tears with minimal retraction, ACL treatment with percutaneous injection of BMC and platelet products shows promise as a non-surgical alternative. However, a larger randomized controlled trial is warranted to confirm these findings.Trial registration NCT03011398. A Clinical Registry of Orthobiologics Procedures. https://clinicaltrials.gov/ct2/show/NCT03011398?term=orthobiologics&rank=1. Registered 29 December 2016. Enrollment 1 December 2011-retrospectively registered

Background: Bone marrow lesions are a radiographic indication of bony pathology closely associated with advanced osteoarthritis of the adjacent joint. Injection of autologous orthobiologic products, including bone marrow concentrate and platelet-rich plasma, have demonstrated safety and efficacy in treating both advanced osteoarthritis (via intraarticular injection) and associated bone marrow lesions (via intraosseous injection). The relative efficacy of intraarticular versus intraosseous injection of orthobiologics has not been evaluated at the present time. Objectives: The objective was to evaluate differences in orthobiologic bone marrow lesions treatment, either as a collateral result of intraarticular injection with bone marrow concentrate and platelet products alone, or intraosseous plus intraarticular injection as measured by patient reported outcomes. Study Design: This study employed a prospective case-matched cohort design. Setting: This study took place at a single outpatient interventional orthopedic pain clinic. Methods: Using data from a prospective orthobiologic treatment registry of knee patients, a population of knee osteoarthritis with bone marrow lesions patients who had undergone only intraarticular knee injections of bone marrow concentrate and platelets (for symptomatic advanced osteoarthritis) were age, gender, and disease severity case-matched to a series of advanced osteoarthritis and bone marrow lesions patients who underwent intraosseous plus intraarticular injections. Self-reported patient outcomes for Numeric Pain Scale, International Knee Documentation Committee, lower extremity functional scale, and a modified single assessment numeric evaluation were compared between the 2 treatment groups. Results: Eighty patients were included, 40 in each group. Although pain and functional outcome scores were significantly improved in both treatment groups, there was no statistically significant differences in patient reported outcomes based on the type of treatment. Limitations: There are several limitations to this study, including multiple providers performing the injections, varying onset of symptoms to treatment, and additional injections after their initial treatment, that were not controlled. In addition, increasing the sample size may be beneficial as well, particularly with the large bone marrow lesions group, which did suggest possible improvement with intraosseous plus intraarticular over the intraarticular, although was not statistically significant in our sample. Limited data availability for this cohort as well as some missing data are other limitations to consider. Conclusion: Treating knee bone marrow lesions with intraosseous bone marrow concentrate and platelet products did not affect patient reported outcomes. Key words: Intraosseous, intraarticular, bone marrow concentrate, bone marrow lesion, bone marrow edema, knee osteoarthritis, platelet-rich plasma, injection

Background: There has been a recent emergence in the use of orthobiologics, including platelet-rich plasma (PRP) and bone marrow concentrate (BMC), in the treatment of various musculoskeletal conditions. The goal of this study was to determine if injection of BMC and platelet products into partial and full-thickness anterior cruciate ligament (ACL) tears can facilitate primary ligament healing in patients failing conservative care, resulting in improved outcomes compared to exercise therapy.Methods: Patients were randomized to either exercise therapy or percutaneous injection of autologous BMC with PRP and platelet lysate into the ACL under fluoroscopic guidance. Pain and function were assessed at baseline and at 1, 3, 6, 12, and 24 months. Baseline and 6-month post-treatment magnetic resonance imaging (MRI) were obtained to evaluate interval healing. Laxity was assessed using the Telos device.Results: There was significant improvement in functional outcomes in the BMC group, compared to base-line for LEFS at time points 3 up to 24 months s = 0.000000005), and significant improvement in pain in the BMC group at 6 (p = 0.00054), 12 (p = 0.00127), and 24 months (p = 0.002). There was no significant improvement in pain or function at any time point in the exercise therapy group. There was significant improvement in ACL MRI ImageJ quantitative assessment in the BMC group (p = 0.001) and no difference in the exercise group (p > 0.05). No serious adverse events were reported.Conclusion: Autologous BMC and platelet product injection into ACL tears improved patient function compared to exercise, observed through 24 months. Patients treated with BMC demonstrated quantitative improvements in post-treatment MRI scans suggestive of interval ligament healing.

Background The increasing burden of musculoskeletal disorders combined with the high utilization of opiates and the relatively limited ability of traditional approaches to satisfactorily address many of these conditions has spurred an increased interest in alternative treatments such as regenerative medicine therapies. Evidence is growing to support the use of regenerative injection treatments, including prolotherapy, platelet-rich plasma (PRP), platelet lysate (PL), and mesenchymal stromal cells. This study aims to offer a proof of concept via a case series of patients with neck pain treated using a functional spinal unit (FSU) model with combination prolotherapy, PRP, and PL injections. Methodology A chart review identified patients with neck pain treated with a combination of cervical injections using concentrated platelets and prolotherapy. Results A total of 14 patients met the inclusion criteria. The average decrease in the Numeric Pain Score was 2.8 (p = 0.002). The mean decrease in the Functional Rating Index was 27.3 (p = 0.004) at 24 months. Two patients had mild adverse reactions. Conclusions This case series demonstrates basic safety and clinically significant improvements in patients treated for neck pain with autologous concentrated platelet products and prolotherapy utilizing an FSU treatment protocol. Additional clinical studies are warranted with a larger patient sample size and longer follow-up periods.