Physical therapy exerts sub-additive and suppressive effects on intracerebral neural stem cell implantation in a rat model of stroke

Intracerebral cell therapy (CT) is emerging as a new therapeutic paradigm for stroke. However, the impact of physical therapy (PT) on implanted cells and their ability to promote recovery remains poorly understood. To address this translational issue, a clinical-grade neural stem cell (NSC) line was implanted into peri-infarct tissue using MRI-defined injection sites, two weeks after stroke. PT in the form of aerobic exercise (AE) was administered 5 × per week post-implantation using a paradigm commonly applied in patients with stroke. A combined AE and CT exerted sub-additive therapeutic effects on sensory neglect, whereas AE suppressed CT effects on motor integration and grip strength. Behavioral testing emerged as a potentially major component for task integration. It is expected that this study will guide and inform the incorporation of PT in the design of clinical trials evaluating intraparenchymal NSCs implantation for stroke.

The Usages and Potential Uses of Alginate for Healthcare Applications

Due to their unique properties, alginate-based biomaterials have been extensively used to treat different diseases, and in the regeneration of diverse organs. A lot of research has been done by the different scientific community to develop biofilms for fulfilling the need for sustainable human health. The aim of this review is to hit upon a hydrogel enhancing the scope of utilization in biomedical applications. The presence of active sites in alginate hydrogels can be manipulated for managing various non-communicable diseases by encapsulating, with the bioactive component as a potential site for chemicals in developing drugs, or for delivering macromolecule nutrients. Gels are accepted for cell implantation in tissue regeneration, as they can transfer cells to the intended site. Thus, this review will accelerate advanced research avenues in tissue engineering and the potential of alginate biofilms in the healthcare sector.

CD133+ Stem Cell Therapy Effects on Myocardial Regeneration Through Increased Vascular Endothelial Growth Factor Correlate with Cardiac Magnetic Resonance Imaging Results in Coronary Artery Bypass Graft Surgery Patients with Low Ejection Fraction

Background: Stem cell implantation has become a promising therapy for heart failure due to coronary heart disease (CHD). CD133+ stem cell therapy, together with increases of vascular endothelial growth factor (VEGF) and other growth hormones, can induce myocardial repair. Objective: To prove that VEGF plays a role in cardiac regeneration. Methods: Twenty-six patients with CHD and ejection fractions <35% from Harapan Kita Heart and Vascular Center, Jakarta, Indonesia, from 2016 to 2018 were randomized into 2 groups. The treatment group underwent coronary artery bypass graft (CABG) + CD133+ implantation, and the control group underwent CABG only. Six months later, perfusion and myocardial function were assessed by ejection fraction, wall motion score index (WMSI), ventricular dimensions, and scar size using cardiovascular magnetic resonance imaging. VEGF was assessed with enzyme-linked immunosorbent assay. Results: There was significant improvement in ejection fraction (8.69% ± 9.49% versus 1.43% ± 7.87%, P = .04), WMSI (0.51 ± 0.48 versus –0.01 ± 0.21, P = .003), and scar size (25.46 ± 12.91 versus 27.32 ± 12.92 mm, P = .047) and a significant increase in blood VEGF levels (61.05 ± 63.01 versus 19.88 ± 33.78 pg/mL, P = .01). Improvements in perfusion defects (13.69 ± 5.03 versus 11.53 ± 5.81 P = .32) and ventricular dimensions (–27.59 ± 84.48 versus –19.08 ± 36.79 mm, P = .06) were not statistically significant. Conclusion: CD133+ stem cell implantation improves myocardial function. The increase in VEGF levels is expected to continue improving restoration of myocardial function when myocardial perfusion improvement is still not optimal.

Clinical observation of a patient with chronic heart failure after mesenchymal stem cell implantation in outpatient conditions

The article presents a case of a successful application of mesenchymal stem cells in clinical practice and provides an analysis of literature sources on this topic, clinical data, and results of laboratory studies.

Circulating microRNA-762 upregulates colorectal cancer may be accompanied by Wnt-1/β-catenin signaling

Colorectal cancer (CRC) has become the third most common cause of cancer-related deaths. CRC occurs because of abnormal growth of cells that can invade other tissues and cause distant metastases. Researchers have suggested that aberrant microRNA (miRNA) expression is involved in the initiation and progression of cancers. However, the key miRNAs that regulate the growth and metastasis of CRC remain unclear. The circulating miRNAs from BALB/c mice with CRC CT26 cell implantation were assayed by microarray. Then, Mus musculus (house mouse) mmu-miR-762 mimic and inhibitor were transfected to CT26 cells for analysis of cell viability, invasion, and epithelial-mesenchymal transition (EMT), cell cycle, and regulatory molecule expression. Human subjects were included for comparison the circulating Homo sapiens (human) has-miR-762 levels in CRC patients and control donors, as well as the patients with and without distant metastasis. The result for miRNA levels in mice with CRC cell implantation indicated that plasma mmu-miR-762 was upregulated. Transfection of mmu-miR-762 mimic to CT26 cells increased cell viability, invasion, and EMT, whereas transfection of mmu-miR-762 inhibitor decreased the above abilities. Cells treated with high-concentration mmu-miR-762 inhibitor induced cell cycle arrest at G0/G1 phase. However, mmu-miR-762 did not cause apoptosis of cells. Western blot analysis showed that mmu-miR-762 mimic transfection upregulated the expression of Wnt-1 and β-catenin, as well as increased the nuclear translocation of β-catenin. Further analysis was performed to demonstrate the correlation of miR-762 with CRC, and blood samples were collected from CRC patients and control donors. The results showed that serum has-miR-762 levels in CRC patients were higher than in control donors. Among the CRC patients (n= 20), six patients with distant metastasis showed higher serum has-miR-762 levels than patients without distant metastasis. Conclusions, the present study suggests that circulating miR-762 might be a potential biomarker for upregulation of CRC cell growth and invasion, and may be accompanied by the Wnt/β-catenin signaling.

Functional Recovery after Intramyocardial Injection of Adipose-Derived Stromal Cells Assessed by Cardiac Magnetic Resonance Imaging

Aims. A major clinical concern is the continuous increase in the number of patients diagnosed with advanced coronary artery disease, ischemic heart failure, and refractory angina, and one of the most promising treatment options for these conditions is stem cell-based therapy. The aim of this study was to assess the functional improvement following intramyocardial injection of adipose-derived stromal cells, using cardiac magnetic resonance. Methods and Results. Thirteen patients with ischemic heart failure, reduced left ventricular ejection fraction, refractory angina, and who have been disqualified from any form of direct revascularization were enrolled in the study with transthoracic autologous adipose-derived stromal cell implantation. All patients underwent cardiac magnetic resonance prior to the procedure and after 12 months of follow-up. A significant increase in stroke volume ( 83.1 ± 8.5 mL vs 93.8 ± 13.8 mL , p = 0.025 ) and stroke volume index ( 43.3 ± 7.6 mL / m 2 vs 48.7 ± 9.1 mL / m 2 , p = 0.019 ), a statistical trend toward an increase in left ventricle ejection fraction ( 36.7 ± 13.2 vs 39.7 ± 14.9 , p = 0.052 ), and cardiac output improvement ( 5.0 ± 0.7 vs 5.5 ± 0.9 , p = 0.073 ) was observed in the patient postprocedure. Enhanced relative regional thickening was noted in the segments with adipose-derived stromal cell implantation. Conclusions. Intramyocardial adipose-derived stromal cell implantation is a promising therapeutic option for selected, symptomatic patients with ischemic heart failure, who have preserved myocardial viability despite being unsuitable for direct revascularization.

Silencing Smad7 potentiates BMP2-induced chondrogenic differentiation and inhibits endochondral ossification in human synovial-derived mesenchymal stromal cells

Background Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factor for cartilage tissue-engineering, but it also induces robust endochondral ossification. Human synovial-derived mesenchymal stromal cells (hSMSCs) have attracted great interest due to their poor potential for differentiation into osteogenic lineages. Smad7 plays a significant in the endochondral ossification. In this study, we explored a new method to amplify the BMP2-induced chondrogenic differentiation of hSMSCs by downregulating Smad7 and applying a cellular scaffold. Methods hSMSCs were isolated from human knee joint synovium from 3 donors through adhesion growth. In vitro and in vivo models of the chondrogenic differentiation of hSMSCs were established. Transgenic expression of BMP2 and silencing of Smad7 and Smad7 was achieved by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining, and RT-PCR analysis of the osteogenic genes RUNX2, Osterix, and Osteocalcin. The chondrogenic differentiation was detected by Alcian blue staining and RT-PCR analysis of the chondrogenic genes SOX9, COL2, and aggrecan. Hypertrophic differentiation was detected by the markers COL10 and MMP13. A subcutaneous stem cell implantation model was established with polyethylene glycol citrate-co-N-isopropylacrylamide (PPCN) scaffolds and athymic nude mice (3/group, 4–6 week-old female) and evaluated by micro-CT, H&E staining, and Alcian blue staining. An immunohistochemistry assay was used to detected COL1 and COL2, and an immunofluorescence assay was used to detect COL10 and MMP13. Results These hSMSCs identified by flow cytometry. These hSMSCs exhibited lower osteo-differentiation potential than iMads and C3H10T1/2-cells. When Smad7 was silenced in BMP2-induced hSMSCs, the chondrogenic differentiation genes SOX9, COL2, and aggrecan were enhanced in vitro. Additionally, it silencing Smad7 led to a decrease in the hypertrophic differentiation genes COL10 and MMP13. In subcutaneous stem cell implantation assays, immunofluorescence and immunohistochemical staining demonstrated that silencing Smad7 increased the number of COL2-positive cells and decreased the expression of COL1, COL10, and MMP13. Conclusion This study suggests that the application of hSMSCs, cell scaffolds, and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibiting the expression of Smad7 in BMP2-induced hSMSC differentiation may be a new strategy for cartilage tissue-engineering.