Nevin Witman

ORCID: 0000-0002-1109-778X
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About
Contact & Profiles
Research Areas
  • Tissue Engineering and Regenerative Medicine
  • Congenital heart defects research
  • Electrospun Nanofibers in Biomedical Applications
  • Pluripotent Stem Cells Research
  • Renal and related cancers
  • Tracheal and airway disorders
  • Neuroscience and Neural Engineering
  • 3D Printing in Biomedical Research
  • RNA Interference and Gene Delivery
  • Mesenchymal stem cell research
  • Vascular Anomalies and Treatments
  • Single-cell and spatial transcriptomics
  • Cardiac electrophysiology and arrhythmias
  • MicroRNA in disease regulation
  • RNA and protein synthesis mechanisms
  • Cardiomyopathy and Myosin Studies
  • Corneal Surgery and Treatments
  • Graphene and Nanomaterials Applications
  • RNA regulation and disease
  • interferon and immune responses
  • Nanoparticle-Based Drug Delivery
  • RNA Research and Splicing
  • Cardiac Fibrosis and Remodeling
  • Innovative Microfluidic and Catalytic Techniques Innovation
  • Cardiovascular Issues in Pregnancy

Karolinska Institutet
2016-2024

Integrated Cardio Metabolic Centre
2021-2022

AstraZeneca (Sweden)
2022

Stockholm University
2011-2013

mRNA can direct dose-dependent protein expression in cardiac muscle without genome integration, but to date has not been shown improve function a safe, clinically applicable way. Herein, we report that purified and optimized biocompatible citrate-saline formulation is tissue specific, long acting, does stimulate an immune response. In small- large-animal, permanent occlusion myocardial infarction models, VEGF-A 165 improves systolic ventricular limits damage. Following single administration...

10.1016/j.omtm.2018.04.003 article EN cc-by-nc-nd Molecular Therapy — Methods & Clinical Development 2018-04-10

Abstract Long segmental repair of trachea stenosis is an intractable condition in the clinic. The reconstruction artificial substitute by tissue engineering a promising approach to solve this unmet clinical need. 3D printing technology provides infinite possibility for trachea. Here, we printed biodegradable reticular polycaprolactone (PCL) scaffold with similar morphology whole segment rabbits’ native 3D-printed was suspended culture chondrocytes 2 (Group I) or 4 II) weeks, respectively....

10.1038/s41598-017-05518-3 article EN cc-by Scientific Reports 2017-07-06

Abstract Embryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that ISL1 , gene with well-established role in cardiogenesis, controls regulatory network amnion. CRISPR/Cas9-targeting of results embryos which do not yield viable offspring, demonstrating critically required embryogenesis. On cellular level, mutant...

10.1038/s41467-021-25186-2 article EN cc-by Nature Communications 2021-08-26

Abstract Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair improve the rate of recovery being intensely investigated. Here, we probed marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding hBMP-2 VEGF-A gene to therapeutically heal bone. Induction osteogenesis from modRNA-treated BMSCs was confirmed by expression...

10.1038/s42003-020-01606-9 article EN cc-by Communications Biology 2021-01-19

Cell-based therapies offer an exciting and novel treatment for heart repair following myocardial infarction (MI). However, these often suffer from poor cell viability engraftment rates, which involve many factors, including the hypoxic conditions of infarct environment. Meanwhile, vascular endothelial growth factor (VEGF) has previously been employed as a therapeutic agent to limit damage simultaneously induce neovascularization. This study took approach transiently overexpress VEGF protein,...

10.1016/j.ymthe.2022.08.012 article EN cc-by-nc-nd Molecular Therapy 2022-08-17

Traditional treatment therapies for tracheal stenosis often cause severe post-operative complications. To solve the current difficulties, novel and more suitable long-term treatments are needed. A whole-segment tissue-engineered trachea (TET) representing native goat was 3D printed using a poly(caprolactone) (PCL) scaffold engineered with autologous auricular cartilage cells. The TET underwent mechanical analysis followed by in vivo implantations order to evaluate clinical feasibility...

10.1002/term.2828 article EN Journal of Tissue Engineering and Regenerative Medicine 2019-02-22

Abstract Background Fat grafting, as a standard treatment for numerous soft tissue defects, remains unpredictable and technique-dependent. Human adipose-derived stem cells (hADSCs) are promising candidates cell-assisted therapy to improve graft survival. As free-living fat requires nutritional respiratory sources thrive, insufficient unstable vascularization still impedes hADSC-assisted therapy. Recently, cytotherapy combined with modified mRNA (modRNA) encoding vascular endothelial growth...

10.1186/s13287-020-02008-8 article EN cc-by Stem Cell Research & Therapy 2020-11-19

Abstract The contribution of the epicardium, outermost layer heart, to cardiac regeneration has remained controversial due a lack suitable analytical tools. By combining genetic marker-independent lineage-tracing strategies with transcriptional profiling and loss-of-function methods, we report here that epicardium highly regenerative salamander species Pleurodeles waltl an intrinsic capacity differentiate into cardiomyocytes. Following cryoinjury, CLDN6 + epicardium-derived cells appear at...

10.1038/s41556-022-00902-2 article EN cc-by Nature Cell Biology 2022-05-01

Stem-cell based in vitro differentiation for disease modeling offers great value to explore the molecular and functional underpinnings driving many types of cardiomyopathy congenital heart diseases. Nevertheless, one major caveat application human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) involves immature phenotype CMs. Most existing methods need complex apparatus require laborious procedures order monitor cardiac differentiation/maturation process often...

10.1021/acsnano.0c01745 article EN ACS Nano 2020-07-01

The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance effective contractions. precise (CMs) along with consistency between CMs essential enhancing physiological accuracy in vitro cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic natural structure. physical, chemical biocompatible properties were rigorously tested. We...

10.3389/fbioe.2023.1094397 article EN cc-by Frontiers in Bioengineering and Biotechnology 2023-02-08

Abstract The dysregulated physical interaction between two intracellular membrane proteins, the sarco/endoplasmic reticulum Ca 2+ ATPase and its reversible inhibitor phospholamban, induces heart failure by inhibiting calcium cycling. While phospholamban is a bona-fide therapeutic target, approaches to selectively inhibit this protein remain elusive. Here, we report in vivo application of acting antibodies (intrabodies), derived from variable domain camelid heavy-chain antibodies, modulate...

10.1038/s41467-022-29703-9 article EN cc-by Nature Communications 2022-05-31

Abstract Engineering a conduction‐consistent cardiac patch has direct implications to biomedical research. However, there is difficulty in obtaining and maintaining system that allows researchers study physiologically relevant development, maturation, drug screening due the issues around inconsistent contractions of cardiomyocytes. Butterfly wings have special nanostructures arranged parallel, which could help generate alignment cardiomyocytes better mimic natural heart tissue structure....

10.1002/btm2.10522 article EN cc-by Bioengineering & Translational Medicine 2023-04-14

Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- cell-based therapies to improve cardiac function. The safe efficient delivery of these solid organs is challenging. Herein, we demonstrate the feasibility using an endovascular intramyocardial approach safely administer mRNA drug products perform cell transplantation procedures in swine. Using

10.1016/j.omtm.2024.101225 article EN cc-by Molecular Therapy — Methods & Clinical Development 2024-02-27

Ventricular-like human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibit the electrophysiological characteristics of spontaneous beating. Previous studies demonstrated that dexmedetomidine (DMED), a highly selective and widely used α2-adrenoceptor agonist for sedation, analgesia, stress management, may induce antiarrhythmic effects, especially ventricular tachycardia. However, underlying mechanisms DMED-mediated effects remain to be fully elucidated.A conventional...

10.21037/atm-20-5898 article EN Annals of Translational Medicine 2021-03-01

Abstract Cardiogenic growth factors play important roles in heart development. Placental factor (PLGF) has previously been reported to have angiogenic effects; however, its potential role cardiogenesis not yet determined. We analyze single-cell RNA-sequencing data derived from human and primate embryonic hearts find PLGF shows a biphasic expression pattern, as it is expressed specifically on ISL1 + second field progenitors at an earlier stage vascular smooth muscle cells (SMCs) endothelial...

10.1038/s41467-023-41305-7 article EN cc-by Nature Communications 2023-09-05

Abstract Essential genes for murine embryonic development can demonstrate a disparate phenotype in human cohorts. By generating transcriptional atlas containing >30,000 cells from postimplantation non-human primate embryos, we discovered that ISL1 , gene with well-established role cardiogenesis, controls regulatory network amnion. CRISPR/Cas9-targeting of resulted embryos which did not yield viable offspring, demonstrating is critically required embryogenesis. On cellular level, mutant...

10.1101/2020.05.28.118703 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2020-05-28
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