Bone Using Stem Cells for Maxillofacial Bone Disorders: A Systematic Review and Meta-analysis.

Due to economic, cultural, environmental, and social factors, the prevalence of maxillofacial bone disorders varies in different parts of the world. The present meta-analysis was conducted to assess the efficacy and safety of different type of stem cells-based scaffolds and their construction methods in maxillofacial bone disorders. We searched major indexing databases, including PubMed/Medline, ISI Web of Science, Scopus, Embase, and Cochrane Central without any language, study region, or type restrictions. A systematic search of articles published up to July 2021 was done. Of the 428 studies found through initial searches, 36 met the inclusion criteria. After applying the exclusion criteria, the main properties of 32 articles on 643 animals and 4 experimental studies on 52 patients (age range from 43 to 74 years) included in this meta-analysis. Our pooled analysis showed that stem cells-based scaffolds significantly improved the bone regeneration and formation in maxillofacial bone disorders (Prevalence: 0.54; 95% CI: 0.43, 0.64, P < 00001, I2 = 90 2). According to the results of these studies, in most studies, bone marrow-derived mesenchymal stem cells (BMSCs) have been used to regenerate bone, and these cells are still the gold standard in bone tissue engineering, a growth factor that is one of the three sides of the tissue engineering triangle. Bone morphogenetic proteins (BMP) especially BMP2 and platelet-rich plasma (PRP) are the most widely used growth factor and scaffold respectively. Platelet-rich plasma (PRP) is used as a scaffold and since it contains proteins, it also used as a growth factor and can be a stimulant of ossification. It seems that the future perspective of bone tissue engineering is to use the prototyping rapid method to build a composite and patient-specific scaffold from CT and MRI images, along with genetically modified stem cells.

Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics.

Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics.

Preclinical-to-clinical innovations in stem cell therapies for liver regeneration.

Acute and chronic liver diseases are the major cause of high morbidity and mortality globally. Liver transplantation is a widely used therapeutic option for liver failure. However, the shortage of availability of liver donors has encouraged research on the alternative approach to liver regeneration. Cell-based regenerative medicine is the best alternative therapy to cater to this need. To date, advanced preclinical approaches have been undertaken on stem cell differentiation and their use in liver tissue engineering for generating efficacious and promising regenerative therapies. Advancements in the bioengineering of stem cells, and organoid generation are the way forward to efficient therapies against liver injury. This review summarizes the recent approaches for stem cell therapy-based liver regeneration and their proof of concepts for clinical application, bioengineering liver organoids to alleviate the liver failure caused due to chronic liver diseases.

Enhanced PDGFR/Wnt/ß-catenin activity of mesenchymal stem cells with high migration ability rescue bone loss of osteoporosis.

Osteoporosis is a widespread disease characterized by bone mass loss and microarchitectural deterioration. The side effects of clinical drugs make mesenchymal stem cells (MSCs)-based therapy gain increasing focus in the treatment of osteoporosis. MSCs need to migrate to the site of damage and undergo differentiation in order to participate in the subsequent bone repair process. Therefore, the homing ability of MSCs may be related to the repair ability. Here, we proposed a novel method to screen MSCs with high migration capacity and confirmed that these MSCs exhibited higher osteogenic differentiation ability both in vivo and in vitro. Further results indicated that MSCs with high migration ability could partly rescue the bone loss of ovarectomized (OVX) rats. Higher expression of Platelet-derived growth factors receptor ß- (PDGFRß) and more nuclear transduction of ß-catenin in MSCs with high migration ability may be responsible for biological functions. This article may provide a method to improve the efficacy of MSCs-based therapy in the clinic.

Application of nanotechnology in acute kidney injury: From diagnosis to therapeutic implications.

Acute kidney injury (AKI), a major health issue concerning ~50% of patients treated in intensive care units, generally leads to severe renal damage associated with high mortality rate. The application of nanotechnology for the management of AKI has profound potential of further development, providing innovative strategies for predicting the early onset and progression of renal disease and improving the treatment efficacy of the life-threating AKI. This review has comprehensively summarized the nanomedicines in the application of AKI diagnosis and emphatically discussed the unique potential of various nanotechnology-based drug delivery systems (e.g., polymeric nanoparticles, organic nanoparticles, inorganic nanoparticles, lipid-based nanoparticles, hydrogels etc.) in the treatment of AKI, allowing for improved therapeutic index by enhancing both efficacy and safety concurrently. These approaches may mechanically mitigate oxidative stress, inflammation, and mitochondrial and other organellar damage, etc. In addition, the combination of nanotechnology with stem cells-based therapy or gene therapy has been explored for reducing renal tissues damage and promoting kidney repair or recovery from AKI. The review provides insights into the synthesis, advantages, and limitations of innovative nanomedicine application in the early detection and effective treatment of AKI.

Intracellular calcium current disorder and disease phenotype in OBSCN mutant iPSC-based cardiomyocytes in arrhythmogenic right ventricular cardiomyopathy.

Obscurin participates in the development of striated muscles and maintenance of the functional sarcoplasmic reticulum. However, the role of obscurin in arrhythmogenic right ventricular cardiomyopathy (ARVC) is not well understood. We aimed to study the novel obscurin mutations in the pathogenesis of ARVC and the underlying mechanisms. Methods: We generated induced pluripotent stem cells (iPSC) through retroviral reprogramming of peripheral blood mononuclear cells isolated from a 46-year-old female diagnosed with ARVC, carrying a mutation in OBSCN. The cells differentiated into functional iPSC-based cardiomyocytes (iPSC-CMs), whose phenotype was determined by transmission electron microscopy, electrophysiological description, immunofluorescence staining, and Oil Red O staining. Molecular characterization was performed by bioinformatic analyses, and identification by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results: ARVC-iPSC-CMs mutation in OBSCN showed significant accumulation of lipids, increased pleomorphism, irregular Z-bands, and increased L type calcium currents. Functional enrichment analysis identified pathways involved in focal adhesion and structure formation; the adipocytokines and PPAR signaling pathways were also activated in the ARVC group. Moreover, our results from ultra-high-resolution microscopy, qRT-PCR and Western blotting confirmed that the mutant OBSCN protein and its anchor protein, Ank1.5, showed structural disorder and decreased expression, but there was increased expression of junctional protein N-Cadherin. Further analysis revealed the gene expression of other desmosomal proteins in ARVC-iPSC-CMs was also decreased but some adipogenesis pathway-related proteins (PPARγ, C/EBPα, and FABP4) were increased. Conclusion: A novel frameshift mutation in OBSCN caused phenotypic alteration accompanied by disrupted localization and decreased expression of its anchoring protein Ank1.5. Furthermore, there was an accumulation of lipids with an increase in fatty fibrosis area and myocardial structural disorder, possibly leading to dysrhythmia in calcium channel-related myocardial contraction. These observations suggested the possibility of attenuating ARVC progression by therapeutic modulation of OBSCN expression.