Evolving Role of Exosomes in Plastic and Reconstructive Surgery and Dermatology.

Exosomes, or extracellular vesicles, represent the latest cell-free addition to the regenerative medicine toolkit. In vitro preclinical studies have demonstrated the safety and efficacy of exosomes, which vary based on source and biomanufacturing, for a myriad of potential therapeutic applications relevant to skin and soft tissue reconstruction. Primary search was performed in September 2021 on the MEDLINE database via PubMed and Ovid, with focus on articles about therapeutic application of exosomes or extracellular vesicles.

Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair.

A Comparative Study of Two Topical Treatments for Photoaging of the Hands.

Background: Multiple effective treatments exist for correction of skin photoaging. Topical L-ascorbic acid (vitamin C), a well-known antioxidant and topical human platelet extract (HPE), is a novel off-the-shelf cosmetic ingredient that has shown positive results in recent clinical studies. HPE is a leukocyte-depleted allogeneic product derived from United States-sourced, pooled, apheresed platelets produced with consistent batch quality, purity, and effect.

Safety and efficacy of human platelet extract in skin recovery after fractional CO laser resurfacing of the face: A randomized, controlled, evaluator-blinded pilot study.

Background: Fractional carbon dioxide (CO ) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising.

Aims: The primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO ablative laser resurfacing treatment to the entire face versus standard of care.

Teaching the process of science with primary literature: Using the CREATE pedagogy in ecological courses.

There have been numerous calls for improved pedagogical practices in biological education, and there is a clear need for such improvements in ecology and related curricula. Most ecology-related texts lack pedagogy and are designed to be content-rich. National initiatives, such as provide guidance on undergraduate biology education, including increasing use of evidence-based active learning, and taking a more conceptual and science practice skills approach.

The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and Enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization.

Bone formation is controlled by histone modifying enzymes that regulate post-translational modifications on nucleosomal histone proteins and control accessibility of transcription factors to gene promoters required for osteogenesis. Enhancer of Zeste homolog 2 (EZH2/Ezh2), a histone H3 lysine 27 (H3K27) methyl transferase, is a suppressor of osteoblast differentiation. Ezh2 is regulated by SET and MYND domain-containing protein 2 (SMYD2/Smyd2), a lysine methyltransferase that modifies both histone and non-histone proteins.

Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence.

Urinary incontinence afflicts up to 40% of adult women in the United States. Stress urinary incontinence (SUI) accounts for approximately one-third of these cases, precipitating ~200,000 surgical procedures annually. Continence is maintained through the interplay of sub-urethral support and urethral sphincter coaptation, particularly during activities that increase intra-abdominal pressure.

MicroRNA-101a enhances trabecular bone accrual in male mice.

High-throughput microRNA sequencing was performed during differentiation of MC3T3-E1 osteoblasts to develop working hypotheses for specific microRNAs that control osteogenesis. The expression data show that miR-101a, which targets the mRNAs for the epigenetic enzyme Ezh2 and many other proteins, is highly upregulated during osteoblast differentiation and robustly expressed in mouse calvaria. Transient elevation of miR-101a suppresses Ezh2 levels, reduces tri-methylation of lysine 27 in histone 3 (H3K27me3; a heterochromatic mark catalyzed by Ezh2), and accelerates mineralization of MC3T3-E1 osteoblasts.

Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results.

Background: Exosomes are regenerative mediators for skin rejuvenation. Human platelet extract (HPE) is an allogeneic exosome product derived from US-sourced, leukocyte-reduced apheresed platelets with consistent purity and potency.

Objectives: The authors sought to better characterize the safety and tolerability of novel HPE (plated) Intensive Repair Serum (Rion Aesthetics, Rochester, MN) and its maximal effects on skin rejuvenation at 6 weeks.

Far migration of an intrauterine contraceptive device from the uterus to the small bowel.

A sexually active, asymptomatic 44-year-old presented for Intrauterine device (IUD) removal that had been in place for 13 years. IUD removal was unsuccessful as the strings could not be located. Imaging revealed an extrauterine IUD and at surgical removal of the abdominal IUD a small bowel perforation requiring bowel resection was required.

Brd4 is required for chondrocyte differentiation and endochondral ossification.

Differentiation of multi-potent mesenchymal stromal cells (MSCs) is directed by the activities of lineage-specific transcription factors and co-factors. A subset of these proteins controls the accessibility of chromatin by recruiting histone acetyl transferases or deacetylases that regulate acetylation of the N-termini of H3 and H4 histone proteins. Bromodomain (BRD) proteins recognize these acetylation marks and recruit the RNA pol II containing transcriptional machinery.

Brd4 Inactivation Increases Adenoviral Delivery of BMP2 for Paracrine Stimulation of Osteogenic Differentiation as a Gene Therapeutic Concept to Enhance Bone Healing.

Bromodomain (BRD) proteins are histone code interpreters that recognize acetylated lysines and link the dynamic state of chromatin with the transcriptional machinery. Here, we demonstrate that ablation of the Brd4 gene in primary mouse bone marrow-derived mesenchymal stem cells via a conditional Brd4 allele suppresses osteogenic lineage commitment. Remarkably, loss of Brd4 function also enhances expression of genes in engineered adenoviral vectors, including Cre recombinase and green fluorescent protein (GFP).

Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.

Mechanical loading-related strains trigger bone formation by osteoblasts while suppressing resorption by osteoclasts, uncoupling the processes of formation and resorption. Osteocytes may orchestrate this process in part by secreting sclerostin (SOST), which inhibits osteoblasts, and expressing receptor activator of nuclear factor-κB ligand (RANKL/TNFSF11) which recruits osteoclasts. Both SOST and RANKL are targets of the master osteoblastic transcription factor RUNX2.

Multiple pharmacological inhibitors targeting the epigenetic suppressor enhancer of zeste homolog 2 (Ezh2) accelerate osteoblast differentiation.

Skeletal development and bone formation are regulated by epigenetic mechanisms that either repress or enhance osteogenic commitment of mesenchymal stromal/stem cells and osteoblasts. The transcriptional suppressive trimethylation of histone 3 lysine 27 (H3K27me3) hinders differentiation of pre-committed osteoblasts. Osteoblast maturation can be stimulated by genetic loss of the H3K27 methyltransferase Ezh2 which can also be mimicked pharmacologically using the classical Ezh2 inhibitor GSK126.

Emerging workforce readiness in regenerative healthcare.

The biology of regenerative medicine has steadily matured, providing the foundation for randomized clinical trials and translation into validated applications. Today, the growing regenerative armamentarium is poised to impact disease management, yet a gap in training next-generation healthcare providers, equipped to adopt and deliver regenerative options, has been exposed. This special report highlights a multiyear experience in developing and deploying a comprehensive regenerative curriculum for medical trainees.

Biological functions of chromobox (CBX) proteins in stem cell self-renewal, lineage-commitment, cancer and development.

Epigenetic regulatory proteins support mammalian development, cancer, aging and tissue repair by controlling many cellular processes including stem cell self-renewal, lineage-commitment and senescence in both skeletal and non-skeletal tissues. We review here our knowledge of epigenetic regulatory protein complexes that support the formation of inaccessible heterochromatin and suppress expression of cell and tissue-type specific biomarkers during development. Maintenance and formation of heterochromatin critically depends on epigenetic regulators that recognize histone 3 lysine trimethylation at residues K9 and K27 (respectively, H3K9me3 and H3K27me3), which represent transcriptionally suppressive epigenetic marks.

Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.

Mechanical loading-related strains trigger bone formation by osteoblasts while suppressing resorption by osteoclasts, uncoupling the processes of formation and resorption. Osteocytes may orchestrate this process in part by secreting sclerostin (SOST), which inhibits osteoblasts, and expressing receptor activator of nuclear factor-κB ligand (RANKL/TNFSF11) which recruits osteoclasts. Both SOST and RANKL are targets of the master osteoblastic transcription factor RUNX2.

Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2.

Bone-stimulatory therapeutics include bone morphogenetic proteins ( BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade.

Molecular pathology of human knee arthrofibrosis defined by RNA sequencing.

Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA).

Functional expression of ZNF467 and PCBP2 supports adipogenic lineage commitment in adipose-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stromal/stem cells (BMSCs) have the potential to be employed in many different skeletal therapies. A major limitation to utilizing BMSCs as a therapeutic strategy in human disease and tissue regeneration is the low cell numbers obtained from initial isolation necessitating multiple cell passages that can lead to decreased cell quality. Adipose-derived mesenchymal stromal/stem cells (AMSCs) have been proposed as an alternative cell source for regenerative therapies; however the differentiation capacity of these cells differs from BMSCs.

β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2.

During bone marrow stromal cell (BMSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin plays a critical role in the Wnt signaling pathway to facilitate downstream effects on gene expression. We show that β-catenin was additive with cytoskeletal signals to prevent adipogenesis, and β-catenin knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized.

The epigenetic reader Brd4 is required for osteoblast differentiation.

Transcription networks and epigenetic mechanisms including DNA methylation, histone modifications, and noncoding RNAs control lineage commitment of multipotent mesenchymal progenitor cells. Proteins that read, write, and erase histone tail modifications curate and interpret the highly intricate histone code. Epigenetic reader proteins that recognize and bind histone marks provide a crucial link between histone modifications and their downstream biological effects.

Cobalt and Chromium Ion Release in Metal-on-Polyethylene and Ceramic-on-Polyethylene THA: A Simulator Study With Cellular and Microbiological Correlations.

Background: The aims of this study were to determine the levels of cobalt (Co) and chromium (Cr) ions generated in simulators from metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) constructs. Furthermore, we aimed to investigate the cytotoxic effect of these ion levels on native tissues and their potential to modify periprosthetic joint infection risk.

Methods: We used in vitro culture of human adipose-derived mesenchymal stem cells (AMSCs) and Staphylococcus epidermidis cultures, respectively.