Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
J Dent Res ; 101(9): 1015-1024, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1752997

ABSTRACT

Oral tissue regeneration following chronic diseases and injuries is limited by the natural endogenous wound-healing process. Current regenerative approaches implement exogenous systems, including stem cells, scaffolds, growth factors, and plasmid DNA/viral vectors, that induce variable clinical outcomes. An innovative approach that is safe, effective, and inexpensive is needed. The lipid nanoparticle-encapsulated nucleoside-modified messenger RNA (mRNA) platform has proven to be a successful vaccine modality against coronavirus disease 2019, demonstrating safety and high efficacy in humans. The same fundamental technology platform could be applied to facilitate the development of mRNA-based regenerative therapy. While the platform has not yet been studied in the field of oral tissue regeneration, mRNA therapeutics encoding growth factors have been evaluated and demonstrated promising findings in various models of soft and hard tissue regeneration such as myocardial infarction, diabetic wound healing, and calvarial and femoral bone defects. Because restoration of both soft and hard tissues is crucial to oral tissue physiology, this new therapeutic modality may help to overcome challenges associated with the reconstruction of the unique and complex architecture of oral tissues. This review discusses mRNA therapeutics with an emphasis on findings and lessons in different regenerative animal models, and it speculates how we can apply mRNA-based platforms for oral tissue regeneration.


Subject(s)
COVID-19 , Tissue Engineering , Animals , Bone Regeneration/genetics , Humans , Intercellular Signaling Peptides and Proteins , Liposomes , Nanoparticles , RNA, Messenger , Technology , Wound Healing/genetics
2.
Biomolecules ; 10(10)2020 09 27.
Article in English | MEDLINE | ID: covidwho-1295752

ABSTRACT

Acute and chronic skin wounds due to burns, pressure injuries, and trauma represent a substantial challenge to healthcare delivery with particular impacts on geriatric, paraplegic, and quadriplegic demographics worldwide. Nevertheless, the current standard of care relies extensively on preventive measures to mitigate pressure injury, surgical debridement, skin flap procedures, and negative pressure wound vacuum measures. This article highlights the potential of adipose-, blood-, and cellulose-derived products (cells, decellularized matrices and scaffolds, and exosome and secretome factors) as a means to address this unmet medical need. The current status of this research area is evaluated and discussed in the context of promising avenues for future discovery.


Subject(s)
Burns/therapy , Exosomes/transplantation , Hydrogels/therapeutic use , Wound Healing/genetics , Burns/pathology , Cell- and Tissue-Based Therapy/trends , Cellulose/therapeutic use , Exosomes/genetics , Humans , Hydrogels/chemistry , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/cytology , Skin/growth & development , Skin/injuries , Skin/metabolism
3.
Int J Mol Sci ; 21(22)2020 Nov 10.
Article in English | MEDLINE | ID: covidwho-917002

ABSTRACT

Pro-inflammatory cytokines like interleukin-1ß (IL-1ß) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1ß on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1ß and used Atomic Force Microscopy to unveil that IL-1ß significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1ß stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1ß may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1ß-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1ß provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.


Subject(s)
Interleukin-1beta/physiology , Lung/physiology , Actins/metabolism , Adolescent , Adult , Biomechanical Phenomena , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Cell Proliferation/physiology , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Collagen Type III/metabolism , Cyclooxygenase 2/metabolism , Elasticity/drug effects , Elasticity/physiology , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/physiology , Humans , Interleukin-1beta/pharmacology , Lung/cytology , Lung/drug effects , Male , Microscopy, Atomic Force , RNA, Messenger/genetics , RNA, Messenger/metabolism , Regeneration/genetics , Regeneration/physiology , Wound Healing/drug effects , Wound Healing/genetics , Wound Healing/physiology , Young Adult
4.
PLoS Biol ; 18(9): e3000849, 2020 09.
Article in English | MEDLINE | ID: covidwho-748960

ABSTRACT

Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.


Subject(s)
Antiviral Agents/immunology , Betacoronavirus/physiology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Gene Expression Regulation , Humans , Immunity/genetics , Kinetics , Male , Middle Aged , Nasopharynx/immunology , Nasopharynx/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Ribosomal Proteins/genetics , SARS-CoV-2 , Sex Factors , Signal Transduction/genetics , Viral Load , Wound Healing/genetics , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL