Administration Of Bone Marrow Stem Cells Research Articles

Ultrasound combined with SDF-1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model.

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.

Novel transplant of combined platelet-rich fibrin Releasate and bone marrow stem cells prevent bone loss in Ovariectomized osteoporotic mice

BackgroundOsteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture.MethodsIn this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality.Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed.ResultsPostmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control.ConclusionThe systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.

Does stem cell therapy induce myocardial neoangiogenesis? Histological evaluation in an ischemia/reperfusion animal model.

In an experimental model in the rabbit, a myocardial ischemia-reperfusion injury was obtained. Subsequently, the effects of homologous bone marrow stem cell (BMSC) administration were studied. In 21 New Zealand adult rabbits, ischemia/reperfusion damage was induced by temporary occlusion of the anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection at the level of the ischemic zone. We evaluated the proangiogenetic effect of intramyocardial injections of BMSC at the peri-infarcted area. Histological evaluations were made after 20 days from the surgical procedure. In rabbits treated with intramyocardial BMSC administration, we demonstrated histologically capillary neoangiogenesis, without signs of tissue immunological reaction or of generation of new myocardial cells. On the contrary, only minimal neovascular supply was detected in rabbits treated with intravenous administration of BMSC. Only typical signs of ischemic myocardium injury were observed in the control group. These observations suggest that the effect of direct BMSC administration in ischemic myocardium could promote a capillary neoangiogenesis, which helps to prevent ischemic myocardial damage.

The Impact of Stem Cells on Electron Fluxes, Proton Translocation, and ATP Synthesis in Kidney Mitochondria after Ischemia/Reperfusion

Tissue damage by ischemia/reperfusion (I/R) results from a temporary cessation of blood flow followed by the restoration of circulation. The injury depresses mitochondrial respiration, increases the production of reactive oxygen species (ROS), decreases the mitochondrial transmembrane potential, and stimulates invasion by inflammatory cells. The primary objective of this work was to address the potential use of bone marrow stem cells (BMSCs) to preserve and restore mitochondrial function in the kidney after I/R. Mitochondria from renal proximal tubule cells were isolated by differential centrifugation from rat kidneys subjected to I/R (clamping of renal arteries followed by release of circulation after 30 min), without or with subcapsular administration of BMSCs. Respiration starting from mitochondrial complex II was strongly affected following I/R. However, when BMSCs were injected before ischemia or together with reperfusion, normal electron fluxes, electrochemical gradient for protons, and ATP synthesis were almost completely preserved, and mitochondrial ROS formation occurred at a low rate. In homogenates from cultured renal cells transiently treated with antimycin A, the coculture with BMSCs induced a remarkable increase in protein S-nitrosylation that was similar to that found in mitochondria isolated from I/R rats, evidence that BMSCs protected against both superoxide anion and peroxynitrite. Labeled BMSCs migrated to damaged tubules, suggesting that the injury functions as a signal to attract and host the injected BMSCs. Structural correlates of BMSC injection in kidney tissue included stimulus of tubule cell proliferation, inhibition of apoptosis, and decreased inflammatory response. Histopathological analysis demonstrated a score of complete preservation of tubular structures by BMSCs, associated with normal plasma creatinine and urinary osmolality. These key findings shed light on the mechanisms that explain, at the mitochondrial level, how stem cells prevent damage by I/R. The action of BMSCs on mitochondrial functions raises the possibility that autologous BMSCs may help prevent I/R injuries associated with transplantation and acute renal diseases.

Osteogenesis by gradually expanding the interface between bone surface and periosteum enhanced by bone marrow stem cell administration in rabbits

We investigated whether administration of mesenchymal stem cells (MSCs) promotes bone formation at the gap created by periosteal distraction. A mesh plate was placed subperiosteally in rabbit parietal bones. Following elevation of the mesh plate, rabbit MSCs were administered into the gap. Controls received phosphate-buffered saline (PBS). The volume, height, bone mineral density (BMD), and bone mineral content (BMC) of newly formed bone were examined using microcomputed tomography. Histological analysis was performed by hematoxylin and eosin staining and immunohistochemistry for type I collagen and osteocalcin. The experimental group showed significantly increased volume, height, BMD, and BMC in newly formed bone tissues at the gaps compared with the control group (P < .05). The newly formed bone tissues showed both type I collagen and osteocalcin expression in the MSC-administration group. Mesenchymal stem cell administration may be useful to induce osteogenesis at sites of periosteal distraction.

Practical Barriers to Delivering Autologous Bone Marrow Stem Cell Therapy as an Adjunct to Liver Resection

Liver resection has been associated with significant morbidity and mortality due to hepatic dysfunction or hepatic failure in the postoperative period. Autologous bone marrow stem cell (BMSC) therapy may offer the potential to enhance hepatic regeneration in this setting, perhaps increasing the safety of the procedure. Preclinical models and initial translational studies have suggested that autologous BMSC administration can facilitate hepatic regeneration following both acute and chronic liver disease. While translational studies have begun in chronic hepatic disease, translation to hepatic surgical indications has been limited. This review explores the practical barriers currently restricting the delivery of autologous stem cell therapies to enhance hepatic regeneration following liver resection including selection of cell type, cell isolation, therapy delivery, trial design, and assessment of efficacy.

Impact of Timing on Efficacy and Safetyof Intracoronary Autologous Bone Marrow Stem Cells Transplantation in Acute Myocardial Infarction: A Pooled Subgroup Analysis of Randomized Controlled Trials

Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI). Timing of BMSC administration might play an important role in the therapeutic response in AMI patients. A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine (EBM) databases was made on randomized controlled trials with at least 3-month follow-up data for patients with AMI undergoing emergent percutaneous coronary intervention (PCI) and receiving intracoronary BMSC transfer thereafter. A total of 7 trials with 660 patients were available for analysis. Compared to baseline level, BMSC transfer at 4 to 7 days post-AMI significantly improved left ventricular ejection fraction (LVEF; 4.63% increase, 95% confidence interval [CI]: 1.00%-8.26%, P = 0.01), reduced left ventricular (LV) end-systolic dimensions (95% CI: - 0.53 - 0.02, P = 0.03), decreased the incidences of revascularization (odds ratio [OR]: 0.60, 95% CI: 0.37-0.97, P = 0.04), decreased the cumulative clinical events of death or recurrent myocardial infarction (OR: 0.32, 95% CI: 0.11-0.95, P = 0.04), and decreased culprit artery restenosis or ventricular arrhythmia (OR: 0.59, 95% CI: 0.36-0.96, P = 0.03) however these improvements did not reach statistical significance in emergent transfer trials (within 24 hour post-AMI). Compared with emergent transfer, intracoronary BMSC therapy at 4 to 7 days also significantly reduced the incidence of revascularization (P for interaction = 0.02). BMSC transfer at 4 to 7 days post-AMI was superior to that within 24 hours in improving LVEF, decreasing LV end-systolic dimensions, and reducing the incidence of revascularization.

Pilot study to evaluate the safety and feasibility of intracoronary CD133+ and CD133− CD34+ cell therapy in patients with nonviable anterior myocardial infarction

The long-term effect of intracoronary infusion of progenitor cells in patients with chronic ischemic cardiomyopathy. Bone marrow stem-cell administration in patients with myocardial infarction improved myocardial performance and in some studies contributed to favorable left ventricular remodeling. We report on the results of a pilot, single center, controlled safety, and feasibility study, including 24 patients with old, nonviable anterior myocardial infarction. Twelve patients underwent intracoronary administration of selected CD133(+) and CD133(-)CD34(+) progenitor cells and 12 were followed up on medical therapy. Left ventricular volumes and ejection fraction, at rest and during low-dose dobutamine, and myocardial viability, using TL-201 reinjection scintigraphy, were analyzed at baseline and long-term follow-up. Patients in the treatment group experienced a sustained decrease in left ventricular end-diastolic and end-systolic resting volumes (P = 0.008 and P = 0.002, respectively), as well as an improvement in global ejection fraction at rest [from (27.2 +/- 6.8)% to (29.7 +/- 7.3)%, P = 0.016]. Segmental anterior and apical wall perfusion, during TL-201 reinjection, were similarly improved (P = 0.005 and P < 0.001, respectively). One patient developed restenosis at the cell delivery site and one progression of atherosclerosis. During 28.0 +/- 8.7 months of clinical follow-up, only one patient experienced deterioration of heart failure. In the control group, we observed stability in the perfusion defect and deterioration in end-diastolic and end-systolic volumes (P= 0.002 and P = 0.003, respectively) and a nonsignificant decrease in ejection fraction (P = 0.11). Intracoronary infusion of selected CD133(+) and CD133(-)CD34(+) progenitor cells to a previously infarcted and nonviable anterior wall is safe, and results in sustained improvement in segmental myocardial perfusion and in favorable left ventricular remodeling.

Portal Vein Embolization and Autologous CD133+Bone Marrow Stem Cells for Liver Regeneration: Initial Experience

To prospectively evaluate the effectiveness of portal vein embolization (PVE) and CD133(+) bone marrow stem cell (BMSC) administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with large hepatic malignancies. The study was approved by the institutional ethics committee; informed consent was obtained. Thirteen patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In six patients (three men, three women; mean age, 61 years; range, 46-72 years) with a future liver remnant volume (FLRV) below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent BMSC administration to segments II and III (group I). In seven patients (three men, four women; mean age, 69 years; range, 63-75 years) with an FLRV below 25%, PVE alone was performed (group II). Two radiologists blinded to patients' identity and each other's results measured liver and tumor volumes with helical computed tomography. Absolute, relative, and daily FLRV gains were compared by using the t test or the Wilcoxon test. The increase of the mean absolute FLRV in group I from 239.3 mL +/- 103.5 (standard deviation) to 417.1 mL +/- 150.4 was significantly higher than that from 286.3 mL +/- 77.1 to 395.9 mL +/- 94.1 in group II (P = .049). The relative gain of FLRV after PVE in group I (77.3% +/- 38.2) was significantly higher than that in group II (39.1% +/- 20.4) (P = .039). The daily hepatic growth rate in group I (9.5 mL/d +/- 4.3) was significantly superior to that in group II (4.1 mL/d +/- 1.9) (P = .03). Time to surgery was 27 days +/- 11 in group I and 45 days +/- 21 in group II (P = .057). In patients with malignant liver lesions, the combination of PVE with CD133(+) BMSC administration substantially increased hepatic regeneration compared with PVE alone.