Autologous Bone Marrow Aspirate Concentrate Research Articles

Low Back Pain, Disability, and Quality of Life One Year following Intradiscal Injection of Autologous Bone Marrow Aspirate Concentrate.

Degenerative disc disease is a common cause of chronic low back pain. Surgical intervention is an invasive treatment associated with high costs. There is growing interest in regenerative medicine as a less invasive but direct disc treatment for chronic discogenic low back pain. To evaluate clinical improvement of primary discogenic low back pain with intradiscal injection of autologous bone marrow aspirate concentrate (BMAC). Study Design. Prospective cohort study. Setting. Single, multiphysician center. Patients. 32 adult patients undergoing intradiscal injection of autologous BMAC for the treatment of primary discogenic low back pain. Interventions. Intradiscal injection of autologous BMAC. Main Outcome Measures. Primary outcome measure is visual analog back pain scale (VAS back pain). Secondary outcome measures include ODI, VAS leg pain, and EQ-5D-5L scores. Outcomes were compared from baseline to 1 year. Thirty-two patients (56.3% male) with a mean age of 45.9 years were enrolled, giving 92 treated levels. Mean VAS back and leg pain scores improved from 5.4 to 3.0 (p < 0.001) and 2.8 to 1.3 (p = 0.005), respectively. Mean ODI scores decreased from 33.5 to 21.1 (p < 0.001), and EQ-5D-5L scores improved from 0.69 to 0.78 (p = 0.001). Using established MCID values, 59.4% had clinically significant improvement in VAS back pain, 43.8% in VAS leg pain, and 56.3% in ODI scores. Intradiscal injection of autologous BMAC significantly improved low back pain, disability, and quality of life at one year. This study suggests that intradiscal BMAC has the potential to be an effective nonsurgical treatment for chronic discogenic low back pain.

P64. Intradiscal injection of autologous bone marrow aspirate concentrate improves low back pain at one year

<h3>BACKGROUND CONTEXT</h3> Chronic low back pain is one of the leading causes of disability and poor quality of life in the US and worldwide. A common cause of chronic low back pain is degenerative disc disease. Current nonsurgical treatments for degenerative disc disease-associated low back pain are typically effective. However, for patients who fail these treatments, surgical fusion is often used as last line treatment. Surgical treatment is associated with higher health care expenditures and a more invasive procedure. As such, there is growing interest in the field of regenerative medicine and stem cell therapy as a less invasive treatment for low back pain. <h3>PURPOSE</h3> The purpose of this study was to investigate the effect of autologous bone marrow aspirate concentrate (BMAC) on patients with symptomatic lumbar degenereative disc disease at one year. <h3>STUDY DESIGN/SETTING</h3> Single institution prospective cohort study. <h3>PATIENT SAMPLE</h3> A total of 32 adult patients. <h3>OUTCOME MEASURES</h3> Mean ODI, EQ-5D-5L, VAS back pain, and VAS leg pain scores. <h3>METHODS</h3> A total of 32 consecutive patients over the age of 18 years diagnosed with discogenic low back pain clinically or by discography who underwent injection of autologous intradiscal BMAC at a single multi surgeon orthopedic spine center were included in this study. Active smokers and patients who had pain generators other than purely discogenic pain were excluded. For primary analysis, patients completed baseline and 1 year post-injection ODI, VAS back, VAS leg, and EQ-5D-5L questionnaires; their scores were compared over time. Preprocedural lumbar MRIs were reviewed for Modic changes and assigned a Pfirrmann grade. Thirteen postprocedural MRIs were available and reviewed using the same parameters. <h3>RESULTS</h3> Thirty-two patients (56.3% male) with a mean age of 45.9 (range 19-65) underwent BMAC injection between 1 and 6 levels completed 1 year follow up. Mean VAS back and leg scores improved from 54.0 to 30.4 (p < 0.001) and 27.9 to 13.3 (p=0.005), respectively. Mean ODI scores decreased from 33.5 to 21.1 (p < 0.001), and EQ-5D-5L scores improved from 0.69 to 0.78 (p=0.001). Using established minimum clinically important difference values, 59.4% of patients saw a clinically significant improvement in VAS back pain, 43.8% in VAS leg pain, and 56.3% in ODI scores. On pre-procedural MRIs, 62.5% of patients had a Modic score of 1 or 2 and 93.8% had a Pfirrmann grade of 3 or higher. Postprocedural MRIs were available for 13 patients, and 61.5% had no measurable change in Pfirrmann grade. Three patients worsened by one Pfirrmann grade and one improved by 1 grade. <h3>CONCLUSIONS</h3> Intradiscal injection of autologous BMAC was shown to significantly improve pain and quality of life at one year. Additionally, this study meets 88% of recently published AAOS reporting standards for studies relating to mesenchymal stem cells. The results of this study suggest that intradiscal injection of autologous BMAC has the potential to be an effective non-surgical treatment for chronic discogenic low back pain. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Paper 40: Improved Cartilage Healing with Microfracture Augmented with Fisetin &amp; Bone Marrow Aspirate Concentrate in Acute Osteochondral Defect

Paper 40: Improved Cartilage Healing with Microfracture Augmented with Fisetin &amp; Bone Marrow Aspirate Concentrate in Acute Osteochondral Defect

Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study

BackgroundKnee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP.MethodsPain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall).ResultsThe BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively).ConclusionsIntra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections.Graphical abstractIntra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.

Autologous BMAC Therapy Improves Spinal Degenerative Joint Disease in Lower Back Pain Patients.

Spinal degenerative joint disease (DJD) is associated with lower back pain (LBP) arising from the degeneration of intervertebral discs (IVD), facet joints, intertransversarii muscles, and interspinous ligaments among other anatomical structures. To circumvent the socioeconomic burdens and often-problematic surgical options imposed by DJD therapy, cell-based biologic modalities like bone marrow aspirate concentrate (BMAC) have been investigated in pre-clinical and clinical settings, mostly for IVD degeneration (IDD), with encouraging outcomes. In this study, we evaluated the differences in therapeutic benefits of BMAC between IVD- and facet joint-originating chronic LBP. Eighteen patients diagnosed with chronic LBP met the selection criteria. Following discography and provocation testing, 13 patients tested positive and were assigned into IDD-associated LBP (1st arm), while the remaining 5 tested negative and were assigned into facetogenic LBP (2nd arm). Autologous BMAC was injected intradiscally in the 1st arm, while the 2nd arm received posterior spinal chain injections. No procedure-related serious events ensued. Clinical improvement was evaluated over 12 months based on pain and functionality questionnaires (VAS, BPI, RAND-36), opioid use, and changes in disc parameters assessed by magnetic resonance imaging (MRI). Ameliorated VAS and BPI scores differed significantly between both arms in favor of IDD patients who also took significantly less opioids. Average RAND-36 scores showed no significant difference between groups albeit a trend suggesting improvement was observed in IDD patients. MRI scans conducted on IDD patients demonstrated marked elevation in disc height and spinal canal space size without worsening disc quality. Overall, this is the first study investigating the potency of BMAC as an IDD treatment in Canada and the first globally for addressing facetogenic pain using cellular therapy.

Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series.

Administration of platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) has shown some promise in the treatment of neurological conditions; however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury (SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index (ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high (> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28–40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the OhioHealth Institutional Review Board (IRB No. 1204946) on May 16, 2018.

Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial.

Background:Approximately 47 million people in the United States have been diagnosed with arthritis. Autologous platelet-rich plasma (PRP) injections have been documented to alleviate symptoms related to knee osteoarthritis (OA) in randomized controlled trials, systematic reviews, and meta-analyses. Autologous bone marrow aspirate concentrate (BMC) injections have also emerged as a treatment option for knee OA, with a limited clinical evidence base.Purpose:To compare the efficacy of BMC to PRP for the treatment of knee OA regarding pain and function at multiple time points up to 12 months after an injection. We hypothesized that BMC will be more effective in improving outcomes in patients with knee OA.Study Design:Randomized controlled trial; Level of evidence, 2Methods:A total of 90 participants aged between 18 and 80 years with symptomatic knee OA (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaires before and 1, 3, 6, 9, and 12 months after a single intra-articular injection of leukocyte-rich PRP or BMC.Results:There were no statistically significant differences in baseline IKDC or WOMAC scores between the 2 groups. All IKDC and WOMAC scores for both the PRP and BMC groups significantly improved from baseline to 1 month after the injection (P < .001). These improvements were sustained for 12 months after the injection, with no difference between PRP and BMC at any time point.Conclusion:Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. Autologous PRP and BMC showed promising clinical potential as therapeutic agents for the treatment of OA, and while PRP has strong clinical evidence to support its efficacy, BMC has limited support. This study did not prove BMC to be superior to PRP, providing guidance to clinicians treating OA. It is possible that the results were affected by patients knowing that there was no control group.Registration:NCT03289416 (ClinicalTrials.gov identifier).

Combined Bone Marrow Aspirate and Platelet-Rich Plasma for Cartilage Repair: Two-Year Clinical Results.

To evaluate the clinical and biological outcome of combined bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) on a collagen scaffold for treating cartilage lesions in the knee. Ten patients (mean age 29.4 years, range 18-36) suffering from large full-thickness cartilage in the knee were treated with BMAC and PRP from January 2015 to December 2016. In a 1-step procedure autologous BMAC and PRP was seeded onto a collagen scaffold and sutured into the debrided defect. Patients were evaluated by clinical outcome scores (IKDC [International Knee Documentation Committee Subjective Knee Form], KOOS [Knee Injury and Osteoarthritis Outcome Score], and pain score using the Numeric Rating Scale [NRS]) preoperatively, after 3 months, and after 1 and 2 years. Second-look arthroscopies were performed (n = 7) with biopsies of the repair tissue for histology. All patients had magnetic resonance imaging (MRI) preoperatively, after 1 year, and after 2 to 3.5 years with MOCART (magnetic resonance observation of cartilage repair tissue) scores evaluating cartilage repair. After 1 year significant improvements were found in IKDC, KOOS symptoms, KOOS ADL (Activities of Daily Living), KOOS QOL (Quality of Life), and pain at activity. At the latest follow-up significant improvements were seen in IKDC, KOOS symptoms, KOOS QOL, pain at rest, and pain at activity. MRI MOCART score for cartilage repair improved significantly from baseline to 1-year follow-up. Histomorphometry of repair tissue demonstrated a mixture of fibrous tissue (58%) and fibrocartilage (40%). Treatment of cartilage injuries using combined BMAC and PRP improved subjective clinical outcome scores and pain scores at 1 and 2 years postoperatively. MRI and histology indicated repair tissue inferior to the native hyaline cartilage.

Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma.

The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31−CD45−CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31−45−90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP (P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF-β1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31−45−90+105+ cells and higher levels of b-FGF than those of PRP.

Outcome of Autologous Bone Marrow Aspirate Concentrate (BMAC) Transplantation in Patient with Spinal Cord Injury: Our experiences

Outcome of Autologous Bone Marrow Aspirate Concentrate (BMAC) Transplantation in Patient with Spinal Cord Injury: Our experiences

Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production.

BackgroundClinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL).MethodsIn this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors.ResultsWe characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells.ConclusionsOur study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria.Clinical trialsUse of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC): Clinicaltrials.gov NCT01931007. Registered August 26, 2013.MSC for Occlusive Disease of the Kidney: Clinicaltrials.gov NCT01840540. Registered April 23, 2013.Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Clinicaltrials.gov NCT02315027. Registered October 31, 2014.Efficacy and Safety of Adult Human Mesenchymal Stem Cells to Treat Steroid Refractory Acute Graft Versus Host Disease. Clinicaltrials.gov NCT00366145. Registered August 17, 2006.A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis. Clinicaltrials.gov NCT01609283. Registered May 18, 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0370-8) contains supplementary material, which is available to authorized users.

Osteogenic efficacy of bone marrow concentrate in rabbit maxillary sinus grafting

Maxillary sinus grafting is required to increase bone volume in the atrophic posterior maxilla to facilitate dental implant placement. Grafting with autogenous bone (AB) is ideal, but additional bone harvesting surgery is unpleasant. Alternatively, bone substitutes have been used but they limit new bone formation. The strategy of single-visit clinical stem cell therapy using bone marrow aspirate concentrate (BMAC) to facilitate new bone formation has been proposed. This study aimed to assess bone regeneration capacity of autologous BMAC mixed with bovine bone mineral (BBM) in maxillary sinus grafting. Twenty-four white New Zealand rabbits were used and their maxillary sinuses were randomly assigned for grafting with 4 different materials. Rates of new bone apposition in augmented sinuses were measured and bone histomorphometry were examined. Significant increase in the quantity of nucleated cells and colony forming unit-fibroblasts were confirmed in BMAC. Mesenchymal stem cells in BMAC retained their in vitro multi-differentiation capability. Higher rates of mineral appositions in the early period were detected in BBM + BMAC and AB than BBM alone, though they are not significantly different. Graft volume/tissue volumes in BBM and BBM + BMAC were found to be higher than those in AB and sham.

Bone Marrow Aspirate Concentrate and Platelet-rich Plasma Enhanced Bone Healing in Distraction Osteogenesis of the Tibia

During lower limb lengthening, poor bone regeneration is a devastating complication. Several local or systemic applications have been used to promote osteogenesis, and biologic stimulations are gaining attention, but their utility has not been proven in this setting. In patients undergoing bilateral tibial lengthening, we compared those receiving an osteotomy site injection of autologous bone marrow aspirate concentrate (BMAC) plus platelet-rich plasma (PRP) with those not receiving such an injection in terms of external fixator index (time in external fixation divided by amount of lengthening), full weightbearing index (time until a patient was permitted to do full weightbearing divided by amount of lengthening), four cortical healing indexes (time until each cortical union divided by amount of lengthening), and callus shape and type. Twenty-two patients (44 tibias) undergoing bilateral tibial lengthening enrolled in this randomized trial. Two patients were excluded, one due to insufficient radiographic evaluation and one who was lost to followup, leaving 20 patients (40 segments) for inclusion. Ten patients (20 segments) received BMAC combined with PRP injection (treatment group) and 10 patients (20 segments) received no injection (control group). All patients underwent stature lengthening for familial short stature with the lengthening over nail technique. Autologous BMAC combined with PRP was injected at the tibial osteotomy site at the end of the index surgery. Mean distraction rates were similar between groups (0.75 mm/day in the treatment group versus 0.72 mm/day in the control group; p = 0.24). Full weightbearing was permitted when we observed radiographic evidence of healing at two cortices; this assessment was made by the surgeon who was blinded to the treatment each patient received. Minimum followup was 24 months (mean, 28 months; range, 24-34 months). There was no difference in mean external fixator index between groups. However, mean cortical healing indexes (anterior/posterior/medial/lateral) were 1.14/0.81/0.96/0.88 months/cm in the treatment group and 1.47/1.26/1.42/1.22 months/cm in the control group (all p < 0.001), showing faster healing in the treatment group at each cortex. Full weightbearing was permitted earlier in the treatment group than in the control group (index: 0.99 months/cm and 1.38 months/cm, respectively, p < 0.001). Callus shape and type were not different between groups. Autologous BMAC combined with PRP injection at the osteotomy site helped improve bone healing in distraction osteogenesis of the tibia, although the effect size was small. Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

SS1. Safety and Efficiacy of Rapid Autologous Bone Marrow Aspirate Concentrate for the Treatment of Critical Limb Ischemia in Buerger's Disease

SS1. Safety and Efficiacy of Rapid Autologous Bone Marrow Aspirate Concentrate for the Treatment of Critical Limb Ischemia in Buerger's Disease