Intraosseous Injection of Autologous Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma for Treatment of Knee Osteoarthritis

The aim of the study was to determine the effectiveness of autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intraosseous injection in the treatment of patients with knee OA stages II-III. Materials and Methods. The multicenter randomized study involved 40 patients (27 women, 13 men, average age 67.07.8 years, BMI 32.74.8, duration of disease 17.33.7 months) with knee OA of stages II-III according to the Kellgren-Lawrence (K-L) classification. Patients of the main (BMAC group) group (n = 19) underwent a single intraosseous injection of BMAC, in the comparison group (n = 21) a PRP injection (PRP group). The results were evaluated after 1, 3, 6, 12 months with the verbal rating scale (VRS), VAS, Leken and WOMAC scales. Results. Comparison of the results in the groups on the VRS showed that at an earlier time (3 and 6 months), the preferences of patients were in favor of the treatment of BMAC (65% and 55% positive reviews) before PRP (55% and 45% positive reviews), whereas after 12 months the differences were insignificant. Analysis of VAS indicators in patients of both groups indicated a more pronounced decrease in the severity of pain syndrome after BMAC intraosseous injection. The analysis of the Leken scale indicators showed in favor of BMAC throughout the entire observation period, the differences were most pronounced in the first 3 months of observation. The ratio of the values of the WOMAC index in both patients groups indicated statistically significant differences that persisted in all periods of follow-up, the increase in indicators occurred to a lesser extent after the introduction of BMAC compared with PRP. Conclusion. A single intraosseous BMAC injection has an advantage over a similar PRP injection in terms of pain, knee function and physical activity of patients at all follow-up periods. Both methods of treatment are equally safe.

Cardiovascular Effects of Autologous Bone Marrow–Derived Mesenchymal Stromal Cell Therapy With Early Tacrolimus Withdrawal in Renal Transplant Recipients: An Analysis of the Randomized TRITON Study

Background After renal transplantation, there is a need of immunosuppressive regimens that effectively prevent allograft rejection while minimizing cardiovascular complications. This substudy of the TRITON trial evaluated the cardiovascular effects of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in renal transplant recipients. Methods and Results Renal transplant recipients were randomized to MSC therapy, infused at weeks 6 and 7 after transplantation, with withdrawal at week 8 of tacrolimus or standard tacrolimus dose. Fifty‐four patients (MSC group=27; control group=27) underwent transthoracic echocardiography at weeks 4 and 24 after transplantation and were included in this substudy. Changes in clinical and echocardiographic variables were compared. The MSC group showed a benefit in blood pressure control, assessed by a significant interaction between changes in diastolic blood pressure and the treatment group ( P =0.005), and a higher proportion of patients achieving the predefined blood pressure target of <140/90 mm Hg compared with the control group (59.3% versus 29.6%, P =0.03). A significant reduction in left ventricular mass index was observed in the MSC group, whereas there were no changes in the control group ( P =0.002). The proportion of patients with left ventricular hypertrophy decreased at 24 weeks in the MSC group (33.3% versus 70.4%, P =0.006), whereas no changes were noted in the control group (63.0% versus 48.1%, P =0.29). Additionally, MSC therapy prevented progressive left ventricular diastolic dysfunction, as demonstrated by changes in mitral deceleration time and tricuspid regurgitant jet velocity. Conclusions MSC strategy is associated with improved blood pressure control, regression of left ventricular hypertrophy, and prevention of progressive diastolic dysfunction at 24 weeks after transplantation. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03398681.

Combination use of core decompression for osteonecrosis of the femoral head: A systematic review and meta-analysis using Forest and Funnel Plots

Problem statement. Core decompression (CD) is a very significant process of dealing in the treatment of femoral head necrosis. And CD combined with bone marrow mesenchymal stem cell transplantation has been widely used in clinical practice, but its effectiveness is controversial. This study is carried out to observe its efficacy and outcomes. Objective. This study evaluated the efficacy and safety of CD combined with bone marrow stem cells in the treatment of femoral head necrosis by systematic review and meta-analysis. Methodology. PubMed, The Cochrane Library, Embase, CNKI, Google Scholar and MEDLINE, etc. databases were searched for clinical randomized controlled trials (RCTs) comparing core decompression combined with autologous bone marrow mesenchymal stem cells versus core decompression alone in the treatment of femoral head necrosis. The retrieval period is from the establishment of each database to May 20, 2021. After literature was extracted and literature quality was evaluated, meta-analysis was conducted by using RevMan5.3 software. Results. A total of 420 osteonecrosis of the femoral head 452 patients' data were collected from all studies. Compared with the core decompression alone group, the CD combined with bone marrow stem cell showed marked reduction in the Visual analog scale (VAS), enhanced Harris hip score (HHS) at 12 months and 24 months, slowed down the progression of the disease, decreased the number of hips conversed to total hip arthroplasty (THA) in the future. Conclusion. Core decompression therapy is a very effective and safe treatment process used for ONFH. Moreover, CD combined autologous bone marrow stem cell transplantation can improve the survival rate of the necrotic head, reduce hip pain and delay the disease progression, the rate of THA postoperatively.

Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis

Knee osteoarthritis is the most prevalent joint disease and a frequent cause of pain, functional loss and disability. Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells using the Huskisson plot to enhance quantification of efficacy and comparability. We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained 1 year after cell application remained after 2 and 4 years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.Trial registration: EudraCT 2009-017405-11; NCT02123368. Registered 25 April 2014—Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02123368?term=02123368&draw=2&rank=1

Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection

Background: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment. Objective: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings. Methods: We employed high throughput proteomic analysis, enzyme-linked immunosorbent assays and immunoblotting, as well as in vitro assays of enzyme activity and neuroprotection. Results: We demonstrated that, in progressive MS, the MSC secretome has lower levels of mitochondrial fumarate hydratase (mFH). Exogenous mFH restores the in vitro neuroprotective potential of MS-MSC. Furthermore, MS-MSC expresses reduced levels of fumarate hydratase (FH) with downstream reduction in expression of master regulators of oxidative stress. Conclusions: Our findings are further evidence of dysregulation of the bone marrow microenvironment in progressive MS with respect to anti-oxidative capacity and immunoregulatory potential. Given the clinical utility of the fumaric acid ester dimethyl fumarate in relapsing–remitting MS, our findings have potential implication for understanding MS pathophysiology and personalised therapeutic intervention.

Autologous Bone Marrow-Derived Chondrocytes for Patients with Knee Osteoarthritis: A Randomized Controlled Trial

Background and Objective. The aim of this study was to compare the effect of autologous bone marrow-derived chondrocytes (ABMDCs) with pharmacological management of osteoarthritis of knee (OAK) and assess the benefit of the two in the improvement of pain relief, functional betterment, and quality of life (QOL). Patients and Methods. A prospective, randomized study was undertaken in patients with OAK grades II and III of Kellgren–Lawrence grading (KLG) in two groups. Group I had 5 million of intra-articular ABMDC in the affected joint, and Group II continued the nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy as needed. Before the treatment, patients were meticulously examined and data were entered for age, sex, Body Mass Index (BMI), Visual Analogue Scale (VAS), Modified Knee Society Score-Short Form (MKSSSF), and QOL. Patients were followed up for 3, 12, and 24 months to assess efficacy, safety, and tolerability. To assess the cartilage regeneration of the damaged cartilage, magnetic resonance imaging (MRI) was used. Results. There were a total of 60 patients who were followed up. Three patients in Group II were removed from the analysis as they underwent total knee arthroplasty (TKA). A notably significant improvement was noticed in the ABMDC group on all scores of VAS and MKSSSF with P < 0.0001 . The control group continued to be dissatisfied with the treatment they were taking. Conclusions. This study reveals that a single injection of 5 million of ABMDC was efficient in reducing the symptoms, improving the functional score and betterment of QOL.

Autologous Bone Marrow Cell Infusion for the Treatment of Decompensated Liver Cirrhosis Patients With Type 2 Diabetes Mellitus

This study aimed to indicate whether autologous bone marrow cell infusion (ABMI) via the right omental vein (ROV) could have a regulatory effect on decompensated liver cirrhosis (DLC) patients with type 2 diabetes mellitus (T2DM). For this purpose, 24 DLC patients with T2DM were divided into observation group (n=14) and control group (n=10). Patients in the observation group were given ABMI through the ROV and right omental artery (ROA), and cases in the control group received ABMI through the ROV. At 1, 3, 6, and 12months after ABMI, it was revealed that the prothrombin time, the total bilirubin levels, and the amount of ascites were significantly lower, while the serum albumin levels in the two groups were markedly higher compared with those before ABMI (p&lt;0.01), and there was no significant difference between the two groups at each time point (p&gt;0.05). The fasting blood glucose and glycosylated hemoglobin levels at 6 and 12months after ABMI in the two groups significantly decreased compared with those before ABMI (p&lt;0.05 or p&lt;0.01), while the decreased levels in the observation group were more obvious than those in the control group at each time point (p&lt;0.01). The amount of insulin in the observation group at 3, 6, and 12months after ABMI was significantly less than that before ABMI in the control group (p&lt;0.01). In summary, ABMI showed a significant therapeutic efficacy for DLC patients with T2DM through ROV and ROA.

Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients

ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In the present study, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin–) cells were performed every 6 weeks in 20 sporadic ALS patients. The concentrations of various complement components in the cerebrospinal fluid and plasma at different time points after cell injection were quantified using a Luminex multiplex. The results of the complement system were correlated with the level of leukocytes, neutrophils, lymphocytes, fibrinogen and CRP in the peripheral blood and the functional status of ALS patients using Norris and ALS-FRSr scales. The study showed a statistically significant decrease in plasma C3b concentration in all 7th days after cell application. In parallel, a peak decrease in neutrophil count and CRP level was observed on days 5–7, with a simultaneous maximum clinical improvement on days 7–28 of each Lin– cell administration. Adjuvant Lin– cell therapy appears to have the silencing potential on the complement-mediated immune system and thus suppress pro-inflammatory reactions responsible for neurodegeneration. However, further in-depth studies are necessary to address this issue.