Autologous Bone Marrow-derived Cell Therapy Research Articles

Repeat infusion of autologous bone marrow cells in progressive multiple sclerosis – A phase I extension study (SIAMMS II)

BackgroundDuring the safety and feasibility ‘Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)’, intravenous infusion of autologous marrow was well tolerated. The efficacy of the approach is being explored in a placebo-controlled randomised controlled trial (ACTiMuS, NCT01815632) but it is not known whether repeated infusions will be required to optimise benefit. The objective of the current study was to explore the safety and feasibility of repeat treatment with intravenous autologous bone marrow for patients with progressive multiple sclerosis (MS). Methods‘SIAMMS II’ was a prospective, single centre phase I extension study in which participants in the SIAMMS study were offered repeat bone marrow harvest and infusion of autologous, unfractionated bone marrow as a day-case procedure. The primary outcome measure was number of adverse events and secondary outcome measures included change in clinical rating scales of disability, global evoked potential and cranial magnetic resonance imaging (MRI). ResultsIn total, 4 of the 6 participants in the SIAMMS study had repeat bone marrow harvest and infusion of filtered autologous marrow as a day case procedure which was well tolerated. There were no serious adverse effects. Additional outcome measures including clinical scales, global evoked potentials and cranial MRI were stable. ConclusionSIAMMS II demonstrates the safety and feasibility of repeated, non-myeloablative autologous bone marrow-derived cell therapy in progressive MS.

Contemporary Outcomes of Distal Lower Extremity Bypass for Chronic Limb-Threatening Ischemia and A Model-Based Comparison With Autologous Bone Marrow-Derived Cell Therapy for Limb Preservation

The standard of therapy for chronic limb-threatening ischemia (CLTI) is revascularization. However, for patients for whom below-the-knee bypass is indicated, an autologous great saphenous vein (GSV), the optimal conduit, might not be available. For these patients, an alternative conduit, such as a synthetic or cryopreserved biologic graft, will be necessary. Contemporary outcomes of distal bypass with these suboptimal conduits have not been well described, and recent advances in novel nonoperative management such as autologous bone marrow cell (BMC) therapy warrant a comparative analysis as a potential alternative for limb preservation.

Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II)

IntroductionThe ‘Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)’ trial was a safety and feasibility study which examined the effect of intravenous infusion of autologous bone marrow without myeloablative...

Upgraded heart failure therapy leads to an improved outcome of dilated cardiomyopathy in infants and toddlers.

Dilated cardiomyopathy is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after establishing the diagnosis. New strategies are needed to improve the outcome in this high-risk patient population. We present our experience in 38 patients below the age of three years, who were diagnosed with dilated cardiomyopathy and who were treated at our institution between 2006 and 2012. The treatment strategy involved institution of β-blockers and angiotensin-converting enzyme inhibitors as soon as feasible. In selected cases, pulmonary artery banding or intracoronary autologous bone marrow-derived cell therapy was performed. The median age at presentation was six months (range 1-26 months). The median follow-up age was 16 months (range 2-80 months). Kaplan-Meier analysis of survival after dilated cardiomyopathy diagnosis revealed a one-year survival of 97% and a five-year survival of 86%. The rate of freedom from death or heart transplantation was 82% at one year and 69% at five years. Surviving patients who were free of transplantation, at the follow-up at 25 months (3-80 months), showed a significant improvement in left ventricular ejection fraction (from 19±11 to 46±16%) and left ventricular end-diastolic diameter (z-score from 4.6±2.4 to 1.4±1.6). In addition, the levels of B-type natriuretic peptide improved significantly (from 3330±3840 to 171±825 pg/ml). Our data suggest that the clinical approach described here may result in a markedly improved medium-term outcome in young children with dilated cardiomyopathy. Further studies are required to evaluate whether these approaches reduce end-points such as transplantation or death.

Autologous Bone Marrow-Derived Cell Therapy Combined with Physical Therapy Induces Functional Improvement in Chronic Spinal Cord Injury Patients

Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.

Autologous Bone Marrow–Derived Cell Therapy in Patients With Critical Limb Ischemia

Critical Limb Ischemia (CLI) is the most advanced stage of peripheral arterial disease and is usually treated with bypass surgery or endovascular revascularization. However, a considerable proportion of CLI patients are not eligible to these treatment strategies and amputation is often the only option left. In the past decade, research has focused on bone marrow (BM)-derived cell-based strategies that aim at neovascularization to improve limb perfusion. Individual studies did not convincingly prove efficacy of BM-derived cell therapy in CLI patients thus far. Perform a meta-analysis of all randomized controlled trials (RCTs) available that studied BM-derived cell therapy compared to standard care with or without placebo in CLI patients and provide summary efficacy data on this approach. A systematic search in the electronic databases of Medline, Embase, and the Cochrane Controlled Trials Register was performed. All studies were critically appraised and data were extracted and meta-analyzed using a random-effects model. Major amputation and amputation-free survival were considered as the primary endpoints. A total of 12 RCTs jointly including 510 CLI patients were identified and analyzed. The meta-analysis showed beneficial effects of BM-derived cell therapy on both subjective and surrogate objective endpoints, that is, pain score, pain-free walking distance, ankle-brachial index, and transcutaneous oxygen measurements (all P < 0.00001). Overall, the RCTs showed reduced amputation rates in the therapeutic arms of the included trials with a relative risk (RR) on major amputation of 0.58 [95% confidence interval (CI), 0.40-0.84; P = 0.004]. However, when only the placebo-controlled RCTs were considered, the beneficial effect on major amputation rates was considerably reduced and nonsignificant (RR = 0.78; 95% CI, 0.40-1.51; P = 0.46). Amputation-free survival did not significantly differ between the BM treated and the control group (RR = 1.16; 95% CI, 0.92-1.48; P = 0.22). This meta-analysis underlines the promising potential of BM-derived cell therapy in CLI patients. Importantly, the results of placebo-controlled and non-placebo-controlled RCTs seem to diverge, which stresses the necessity to use placebo in the control arms of these trials. Future well-designed larger placebo-controlled RCTs are needed and should include long-term follow-up data to assess durability of treatment effects.