scholarly journals Bioengineering Technologies for Cardiac Regenerative Medicine

2021 ◽  
Vol 9 ◽  
Author(s):  
Mira Chingale ◽  
Dashuai Zhu ◽  
Ke Cheng ◽  
Ke Huang
Keyword(s):  
Regenerative Medicine ◽  
Viral Vectors ◽  
Gene Editing ◽  
Cardiac Tissue ◽  
Expression Patterns ◽  
3D Culture ◽  
Patient Specific ◽  
Cardiac Stem Cells ◽  
Therapeutic Delivery ◽  
Innovative Solutions

Cardiac regenerative medicine faces big challenges such as a lack of adult cardiac stem cells, low turnover of mature cardiomyocytes, and difficulty in therapeutic delivery to the injured heart. The interaction of bioengineering and cardiac regenerative medicine offers innovative solutions to this field. For example, cell reprogramming technology has been applied by both direct and indirect routes to generate patient-specific cardiomyocytes. Various viral and non-viral vectors have been utilized for gene editing to intervene gene expression patterns during the cardiac remodeling process. Cell-derived protein factors, exosomes, and miRNAs have been isolated and delivered through engineered particles to overcome many innate limitations of live cell therapy. Protein decoration, antibody modification, and platelet membranes have been used for targeting and precision medicine. Cardiac patches have been used for transferring therapeutics with better retention and integration. Other technologies such as 3D printing and 3D culture have been used to create replaceable cardiac tissue. In this review, we discuss recent advancements in bioengineering and biotechnologies for cardiac regenerative medicine.

scholarly journals Stem cell therapies and benefaction of somatic cell nuclear transfer cloning in COVID-19 era

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Birbal Singh ◽  
Gorakh Mal ◽  
Vinod Verma ◽  
Ruchi Tiwari ◽  
Muhammad Imran Khan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Drug Testing ◽  
Human Interaction ◽  
Patient Specific ◽  
Wide Range

Abstract Background The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. Main body Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells. Conclusions The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.

Generation of 2.5D lung bud organoid from human induced pluripotent stem cell

2021 ◽  
pp. 1-14
Author(s):  
Xun Xu ◽  
Yan Nie ◽  
Weiwei Wang ◽  
Imran Ullah ◽  
Wing Tai Tung ◽  
...  
Keyword(s):  
Single Cell ◽  
Disease Modeling ◽  
3D Culture ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Homogeneous Distribution ◽  
Cell Seeding ◽  
Differentiation Potential ◽  
Induced Pluripotent ◽  
Defined Culture

Human induced pluripotent stem cells (hiPSCs) are a promising cell source to generate the patient-specific lung organoid given their superior differentiation potential. However, the current 3D cell culture approach is tedious and time-consuming with a low success rate and high batch-to-batch variability. Here, we explored the establishment of lung bud organoids by systematically adjusting the initial confluence levels and homogeneity of cell distribution. The efficiency of single cell seeding and clump seeding was compared. Instead of the traditional 3D culture, we established a 2.5D organoid culture to enable the direct monitoring of the internal structure via microscopy. It was found that the cell confluence and distribution prior to induction were two key parameters, which strongly affected hiPSC differentiation trajectories. Lung bud organoids with positive expression of NKX 2.1, in a single-cell seeding group with homogeneously distributed hiPSCs at 70%confluence (SC_70%_hom) or a clump seeding group with heterogeneously distributed cells at 90%confluence (CL_90%_het), can be observed as early as 9 days post induction. These results suggest that a successful lung bud organoid formation with single-cell seeding of hiPSCs requires a moderate confluence and homogeneous distribution of cells, while high confluence would be a prominent factor to promote the lung organoid formation when seeding hiPSCs as clumps. 2.5D organoids generated with defined culture conditions could become a simple, efficient, and valuable tool facilitating drug screening, disease modeling and personalized medicine.

Inherent hepatocytic heterogeneity determines expression and retention of edited F9 alleles post-AAV/CRISPR infusion

2021 ◽  
Vol 118 (42) ◽  
pp. e2110887118
Author(s):  
Qiang Wang ◽  
Lin Zhang ◽  
Guo-Wei Zhang ◽  
Jian-Hua Mao ◽  
Xiao-Dong Xi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Gene Editing ◽  
Regulatory Region ◽  
Factor Ix ◽  
Host Cells ◽  
Clotting Factor ◽  
Dependent Manner ◽  
Coding Region ◽  
Therapeutic Benefits

Infusing CRISPR/donor-loaded adeno-associated viral vectors (AAV/CRISPR) could enable in vivo hepatic gene editing to remedy hemophilia B (HB) with inherited deficiency of clotting factor IX (FIX). Yet, current regimens focus on correcting HB with simple mutations in the coding region of the F9, overlooking those carrying complicated mutations involving the regulatory region. Moreover, a possible adverse effect of treatment-related inflammation remains unaddressed. Here we report that a single DNA cutting-mediated long-range replacement restored the FIX-encoding function of a mutant F9 (mF9) carrying both regulatory and coding defects in a severe mouse HB model, wherein incorporation of a synthetic Alb enhancer/promoter-mimic (P2) ensured FIX elevation to clinically meaningful levels. Through single-cell RNA sequencing (scRNA-seq) of liver tissues, we revealed that a subclinical hepatic inflammation post-AAV/CRISPR administration regulated the vulnerability of the edited mF9-harboring host cells to cytotoxic T lymphocytes (CTLs) and the P2 activity in a hepatocytic subset–dependent manner via modulating specific sets of liver-enriched transcription factors (LETFs). Collectively, our study establishes an AAV/CRISPR-mediated gene-editing protocol applicable to complicated monogenetic disorders, underscoring the potentiality of improving therapeutic benefits through managing inflammation.

scholarly journals Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

2017 ◽  
Author(s):  
Adriana Buskin ◽  
Lili Zhu ◽  
Valeria Chichagova ◽  
Basudha Basu ◽  
Sina Mozaffari-Jovin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Retinitis Pigmentosa ◽  
Gene Editing ◽  
Autosomal Dominant ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Patient Specific ◽  
Rpe Cells ◽  
Autosomal Dominant Retinitis Pigmentosa

SummaryMutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To understand the molecular basis of this phenotype, we have generated RP type 11 (PRPF31-mutated) patient-specific retinal organoids and retinal pigment epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing of genes encoding pre-mRNA splicing proteins occurred in patient-specific retinal cells and Prpf31+/− mouse retinae, but not fibroblasts and iPSCs, providing mechanistic insights into retinal-specific phenotypes of PRPFs. RPE was the most affected, characterised by loss of apical-basal polarity, reduced trans-epithelial resistance, phagocytic capacity, microvilli, and cilia length and incidence. Disrupted cilia morphology was observed in patient-derived-photoreceptors that displayed progressive features associated with degeneration and cell stress. In situ gene-editing of a pathogenic mutation rescued key structural and functional phenotypes in RPE and photoreceptors, providing proof-of-concept for future therapeutic strategies.eTOCPRPF31 is a ubiquitously expressed pre-mRNA processing factor that when mutated causes autosomal dominant RP. Using a patient-specific iPSC approach, Buskin and Zhu et al. show that retinal-specific defects result from altered splicing of genes involved in the splicing process itself, leading to impaired splicing, loss of RPE polarity and diminished phagocytic ability as well as reduced cilia incidence and length in both photoreceptors and RPE.HighlightsSuccessful generation of iPSC-derived RPE and photoreceptors from four RP type 11 patientsRPE cells express the mutant PRPF31 protein and show the lowest expression of wildtype proteinPRPF31 mutations result in altered splicing of genes involved in pre-mRNA splicing in RPE and retinal organoidsPrpf31 haploinsufficiency results in altered splicing of genes involved in pre-mRNA splicing in mouse retinaRPE cells display loss of polarity, reduced barrier function and phagocytosisPhotoreceptors display shorter and fewer cilia and degenerative featuresRPE cells display most abnormalities suggesting they might be the primary site of pathogenesisIn situ gene editing corrects the mutation and rescues key phenotypes

Abstract 12600: Microrna From Atrial Tissue Harvested During Transseptal Puncture as a Predictor for Non-pv Trigger in Patients Undergoing Af Ablation: Preliminary Results From a Pilot Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Luigi Di Biase ◽  
Aaron Baker ◽  
Xue Yan ◽  
Jason Lee ◽  
Francesco Santoro ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Standard Procedure ◽  
Expression Patterns ◽  
Pulmonary Veins ◽  
Challenge Test ◽  
Inverse Correlation ◽  
Patient Specific ◽  
Af Ablation ◽  
Atrial Tissue ◽  
Nonparametric Correlation

Introduction: Catheter ablation of atrial fibrillation (AF) is the most valid therapeutic option to achieve rhythm control. Pulmonary veins (PV) are the most known trigger of AF, although recently we have become more aware of the importance of non-PV triggers. Expression of microRNA (miRNA) has been shown to be regulated in many cardiovascular disease. We sought to study expression patterns of miRNA in patients (pts) with AF undergoing ablation to facilitate their application as both diagnostic and prognostic markers. Methods: As part of the standard procedure for AF ablation a double transseptal sample of myocardial tissue is obtained via a transseptal needle. The small piece of atrial septal tissue can be retrieved from the needle as a result of piercing the atrial septum. MiRNA was hybridized to microarrays to determine relative levels of miRNAs in the samples. For a subset of the miRNAs we validated expression through quantitative real time PCR. All pts underwent PV-antrum and non-PV trigger ablation guided by isoproterenol challenge test. Results: Atrial tissue of 11 pts undergoing AF ablation has been utilized for MiRNA assessment. Mean age was 61.27 ± 10.5 years and 8 (72.7%) pts were male. Six (54.5 %) pts had paroxysmal AF. During the ablation non-PV triggers were detected in 8 (72.7 %) pts. Recurrence of AF occurred in 3(27.3 %) pts. Expression of miR-21, miR-26a and miR-29a was higher in pts with non-PV triggers, while miR-30c had lower expression in pts who had recurrence of atrial tachyarrhythmias. Spearman’s nonparametric correlation coefficient was calculated and miR-21, miR-26a, miR-29a were positively correlated with non-PV triggers (r = 0.58, p=0.06 for all three miRNAs), while miR-30c level had inverse correlation (r = (-) 0.78 %, p=0.005) with recurrence (Figure). Conclusions: Expression of miR-21, miR-26a, miR-29a correlates with the presence of non-PV triggers. This information could be clinically relevant in planning patient specific procedures.

scholarly journals Genome editing in large animals: current status and future prospects

2019 ◽  
Vol 6 (3) ◽  
pp. 402-420 ◽  
Author(s):  
Jianguo Zhao ◽  
Liangxue Lai ◽  
Weizhi Ji ◽  
Qi Zhou
Keyword(s):  
Regenerative Medicine ◽  
Genome Editing ◽  
Biomedical Research ◽  
Human Disease ◽  
Gene Editing ◽  
Disease Modeling ◽  
Current Status ◽  
Future Prospects ◽  
Recent Advances ◽  
Large Animals

AbstractLarge animals (non-human primates, livestock and dogs) are playing important roles in biomedical research, and large livestock animals serve as important sources of meat and milk. The recently developed programmable DNA nucleases have revolutionized the generation of gene-modified large animals that are used for biological and biomedical research. In this review, we briefly introduce the recent advances in nuclease-meditated gene editing tools, and we outline these editing tools’ applications in human disease modeling, regenerative medicine and agriculture. Additionally, we provide perspectives regarding the challenges and prospects of the new genome editing technology.

scholarly journals Development of a tool-kit for the detection of healthy and injured cardiac tissue based on MR imaging

2017 ◽  
Vol 3 (2) ◽  
pp. 195-198
Author(s):  
Philip Westphal ◽  
Sebastian Hilbert ◽  
Michael Unger ◽  
Claire Chalopin
Keyword(s):  
Contrast Agent ◽  
Cardiac Tissue ◽  
Software Tool ◽  
Ease Of Use ◽  
Free Software ◽  
Patient Specific ◽  
Initial Contour ◽  
Data Sets ◽  
Heart Model ◽  
Data Set

AbstractPlanning of interventions to treat cardiac arrhythmia requires a 3D patient specific model of the heart. Currently available commercial or free software dedicated to this task have important limitations for routinely use. Automatic algorithms are not robust enough while manual methods are time-consuming. Therefore, the project attempts to develop an optimal software tool. The heart model is generated from preoperative MR data-sets acquired with contrast agent and allows visualisation of damaged cardiac tissue. A requirement in the development of the software tool was the use of semi-automatic functions to be more robust. Once the patient image dataset has been loaded, the user selects a region of interest. Thresholding functions allow selecting the areas of high intensities which correspond to anatomical structures filled with contrast agent, namely cardiac cavities and blood vessels. Thereafter, the target-structure, for example the left ventricle, is coarsely selected by interactively outlining the gross shape. An active contour function adjusts automatically the initial contour to the image content. The result can still be manually improved using fast interaction tools. Finally, possible scar tissue located in the cavity muscle is automatically detected and visualized on the 3D heart model. The model is exported in format which is compatible with interventional devices at hospital. The evaluation of the software tool included two steps. Firstly, a comparison with two free software tools was performed on two image data sets of variable quality. Secondly, six scientists and physicians tested our tool and filled out a questionnaire. The performance of our software tool was visually judged more satisfactory than the free software, especially on the data set of lower quality. Professionals evaluated positively our functionalities regarding time taken, ease of use and quality of results. Improvements would consist in performing the planning based on different MR modalities.

scholarly journals Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
James P. Harris ◽  
Justin C. Burrell ◽  
Laura A. Struzyna ◽  
H. Isaac Chen ◽  
Mijail D. Serruya ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regenerative Medicine ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Substantia Nigra Pars Compacta ◽  
Patient Specific ◽  
Motor Deficits ◽  
Nigrostriatal Pathway ◽  
Future Challenges

AbstractParkinson’s disease (PD) is the second most common progressive neurodegenerative disease, affecting 1–2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the entire nigrostriatal pathway—a key goal to recreate feedback pathways to ensure proper dopamine regulation. Although many pharmacological, genetic, and optogenetic treatments are being developed, this article focuses on the evolution of transplant therapies for the treatment of PD, including fetal grafts, cell-based implants, and more recent tissue-engineered constructs. Attention is given to cell/tissue sources, efficacy to date, and future challenges that must be overcome to enable robust translation into clinical use. Emerging regenerative medicine therapies are being developed using neurons derived from autologous stem cells, enabling the construction of patient-specific constructs tailored to their particular extent of degeneration. In the upcoming era of restorative neurosurgery, such constructs may directly replace SNpc neurons, restore axon-based dopaminergic inputs to the striatum, and ameliorate motor deficits. These solutions may provide a transformative and scalable solution to permanently replace lost neuroanatomy and improve the lives of millions of people afflicted by PD.

Sign in / Sign up

Export Citation Format

Share Document