Umbilical Cord-derived Mesenchymal Stem Cells modulate TNF and soluble TNF Receptor 2 (sTNFR2) in COVID-19 ARDS patients.

Objective: We aimed at explaining the mechanism of therapeutic effect of Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in subjects with COVID-19 Acute Respiratory Distress Syndrome (ARDS). Patients with COVID-19 ARDS present with a hyperinflammatory response characterized by high levels of circulating pro-inflammatory mediators, including tumor necrosis factor α and β (TNFα and TNFβ). Inflammatory functions of these TNFs can be inhibited by soluble TNF Receptor 2 (sTNFR2).

The 50 Most Cited Articles in Meniscal Injury Research.

Background: Meniscal injuries are among the most common orthopaedic injuries, with a significant volume of published literature.

Purpose: To perform a comprehensive bibliometric analysis that appropriately evaluates the 50 most cited articles in meniscal research.

Study Design: Cross-sectional study.

Treatment of chronic diabetic foot ulcers with adipose-derived stromal vascular fraction cell injections: Safety and evidence of efficacy at 1 year.

Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes-induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis-induced macroarterial disease can further complicate DFU pathophysiology.

Cumulative Effects of Strontium Ranelate and Impact Exercise on Bone Mass in Ovariectomized Rats.

Objective: To explore the effect of physical exercise (EXE), strontium ranelate (SR), or their combination on bone status in ovariectomized (OVX) rats.

Design: Sixty female Wistar rats were randomized to one of five groups: sham (Sh), OVX (O), OVX+EXE (OE), OVX+SR (OSR), and OVX+EXE+SR (OESR). Animals in EXE groups were subjected to 10 drops per day (45 cm in height); rats in SR groups received 625 mg/kg/day of SR, 5 days/week for 8 weeks.

Increased Mesenchymal Stem Cell Functionalization in Three-Dimensional Manufacturing Settings for Enhanced Therapeutic Applications.

Mesenchymal stem/stromal cell (MSC) exist within their niches as part of heterogeneous cell populations, exhibiting variable stemness potential and supportive functionalities. Conventional extensive 2D MSC expansion, aimed at obtaining clinically relevant therapeutic cell numbers, results in detrimental effects on both cellular characteristics (e.g.

Compressive Properties and Hydraulic Permeability of Human Meniscus: Relationships With Tissue Structure and Composition.

The meniscus is crucial in maintaining knee function and protecting the joint from secondary pathologies, including osteoarthritis. The meniscus has been shown to absorb up to 75% of the total load on the knee joint. Mechanical behavior of meniscal tissue in compression can be predicted by quantifying the mechanical parameters including; aggregate modulus () and Poisson modulus (ν), and the fluid transport parameter: hydraulic permeability ().

Critical survey and panel review of sustained acoustic medicine in the treatment of sports-related musculoskeletal injuries by professional sports athletic trainers.

Background: The purpose of our study was two-fold. First, it was to discover American professional sports athletic trainers' (PSAT) use and opinions regarding the treatment with a small, portable ultrasound Sustained Acoustic Medicine (SAM) device on their athletes. Second, it was to discover the effectiveness of SAM treatment in their professional sports players (PSP).

Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis.

Background: To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis, and secondarily delay articular cartilage damage in vivo.

Methods: Human IFP-MSC immunophenotype, tripotentiality, and transcriptional profiles were assessed in 3D settings.

Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS.

Sustained clinical improvement of Parkinson's disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells.

Cell-based therapy has been studied as an alternative for Parkinson's Disease (PD), with different routes of administration. The superficial fascia and facial muscles possess a rich blood supply, while venous and lymphatic access via the orbit and the cribriform plate provide a route to cerebral circulation. We here document positive clinical effects in two patients with PD treated with autologous adipose-derived stromal vascular fraction (SVF) cell preparation, implanted into the face and nasal cavity.

Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells.

Approximately 70% of advanced breast cancer patients will develop bone metastases, which accounts for ∼90% of cancer-related mortality. Breast cancer circulating tumor cells (CTCs) establish metastatic tumors in the bone after a close interaction with local bone marrow cells including pericytes and osteoblasts, both related to resident mesenchymal stem/stromal cells (BM-MSCs) progenitors. recapitulation of the critical cellular players of the bone microenvironment and infiltrating CTCs could provide new insights into their cross-talk during the metastatic cascade, helping in the development of novel therapeutic strategies.

Adipose-derived stromal vascular fraction (SVF) cells for the treatment of non-reconstructable peripheral vascular disease in patients with critical limb ischemia: A 6-year follow-up showing durable effects.

We previously reported 18-month results post-injection of adipose-derived stromal vascular fraction (SVF) cells in 10 patients with end-stage peripheral vascular disease (PVD) in critical limb ischemia (CLI) and candidates for amputation, secondary to long-standing diabetes and/or arteriosclerotic disease. We documented positive clinical outcomes demonstrating pain relief as a change in the Rutherford score, improvement of ankle-brachial ratios (ABI), complete healing of 6 critical-size ulcers and evidence of neovascularization to the foot by MRI-based angiography. We now report persistency of the effect 6 years post-procedure in five patients and 4 years post-procedure in four additional patients who remained asymptomatic until death due to cardiac causes (patient 3) and lost from the study (patient 1).

Sustained acoustic medicine as a non-surgical and non-opioid knee osteoarthritis treatment option: a health economic cost-effectiveness analysis for symptom management.

Background: Patients diagnosed with osteoarthritis (OA) and presenting with symptoms are seeking conservative treatment options to reduce pain, improve function, and avoid surgery. Sustained acoustic medicine (SAM), a multi-hour treatment has demonstrated improved clinical outcomes for patients with knee OA. The purpose of this analysis was to compare the costs and effectiveness of multi-hour SAM treatment versus the standard of care (SOC) over a 6-month timeframe for OA symptom management.

Infrapatellar Fat Pad/Synovium Complex in Early-Stage Knee Osteoarthritis: Potential New Target and Source of Therapeutic Mesenchymal Stem/Stromal Cells.

The infrapatellar fat pad (IFP) has until recently been viewed as a densely vascular and innervated intracapsular/extrasynovial tissue with biomechanical roles in the anterior compartment of the knee. Over the last decade, secondary to the proposition that the IFP and synovium function as a single unit, its recognized tight molecular crosstalk with emerging roles in the pathophysiology of joint disease, and the characterization of immune-related resident cells with varying phenotypes (e.g.

Effects of flexibility and strength training on peak hamstring musculotendinous strains during sprinting.

Background: Hamstring injury is one of the most common injuries in sports involving sprinting. Hamstring flexibility and strength are often considered to be modifiable risk factors in hamstring injury. Understanding the effects of hamstring flexibility or strength training on the biomechanics of the hamstring muscles during sprinting could assist in improving prevention strategies and rehabilitation related to these injuries.

Regulatory-compliant conditions during cell product manufacturing enhance in vitro immunomodulatory properties of infrapatellar fat pad-derived mesenchymal stem/stromal cells.

Background Aims: Mesenchymal stem/stromal cell (MSC)-based therapies have gained attention as potential alternatives for multiple musculoskeletal indications based on their trophic and immunomodulatory properties. The infrapatellar fat pad (IFP) serves as a reservoir of MSCs, which play crucial roles modulating inflammatory and fibrotic events at the IFP and its neighboring tissue, the synovium. In an effort to comply with the existing regulatory framework regarding cell-based product manufacturing, we interrogated the in vitro immunomodulatory capacity of human-derived IFP-MSCs processed under different conditions, including a regulatory-compliant protocol, in addition to their response to the inflammatory and fibrotic environments often present in joint disease.

CD10/Neprilysin Enrichment in Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells Under Regulatory-Compliant Conditions: Implications for Efficient Synovitis and Fat Pad Fibrosis Reversal.

Background: Synovitis and infrapatellar fat pad (IFP) fibrosis participate in various conditions of the knee. Substance P (SP), a neurotransmitter secreted within those structures and historically associated with nociception, also modulates local neurogenic inflammatory and fibrotic responses. Exposure of IFP mesenchymal stem cells (IFP-MSCs) to a proinflammatory/profibrotic environment (ex vivo priming with TNFα, IFNγ, and CTGF) induces their expression of CD10/neprilysin, effectively degrading SP in vitro and in vivo.

Signature quality attributes of CD146 mesenchymal stem/stromal cells correlate with high therapeutic and secretory potency.

CD146 bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) play key roles in the perivascular niche, skeletogenesis, and hematopoietic support; however, comprehensive evaluation of therapeutic potency has yet to be determined. In this study, in vitro inflammatory priming to crude human BM-MSCs (n = 8) captured a baseline of signature responses, including enriched CD146 with coexpression of CD107a , CXCR4 , and LepR , transcriptional profile, enhanced secretory capacity, and robust immunomodulatory secretome and function, including immunopotency assays (IPAs) with stimulated immune cells. These signatures were significantly more pronounced in CD146 (POS)-sorted subpopulation than in the CD146 (NEG).

Intralesional Injection of Bone Marrow Aspirate Concentrate for the Treatment of Osteonecrosis of the Knee Secondary to Systemic Lupus Erythematosus: A Case Report.

An 18-year-old female patient with Systemic Lupus Erythematosus (SLE) and corticosteroid-associated extensive bilateral symptomatic knee Osteonecrosis (ON) (Ficat IV), treated with sequential intralesional injections of autologous bone marrow aspirate concentrate (BMAC) under ultrasound guidance. At 3 months, pain was almost absent (VAS) and KOOS/WOMAC showed significant improvement sustained up to 24 months. At 12 months MRI indicated bone maturation, significantly reduced BM edema and subchondral fluid volume, and no collapse/fragmentation signs.

Modulation of Adipose-Derived Mesenchymal Stem/Stromal Cell Transcriptome by G-CSF Stimulation.

Mesenchymal stem/stromal cells (MSCs) exhibit multidifferentiation potential, paralleled with immunomodulatory and trophic properties that make them viable alternative tools for the treatment of degenerative disorders, allograft rejection, autoimmune diseases, and tissue regeneration. MSC functional attributes can be modulated by exposing them to inflammatory-stimulating microenvironments (, priming) before their therapeutic use. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that plays key roles in immune response and hematopoiesis modulation through direct effects on hematopoietic progenitors' proliferation, survival, and mobilization.

MRI of Superior Capsular Reconstruction.

Massive irreparable rotator cuff tears can be a challenging problem for arthroscopists in the perioperative setting because the typical treatment, reverse total shoulder arthroplasty, may not be the best option for all patients. Superior capsular reconstruction (SCR) is an advancing treatment option for patients with rotator cuff tears that are neither amenable to primary repair nor ideal for arthroplasty. Patient selection, which is strongly dependent on preoperative imaging findings, is an important step in obtaining favorable surgical outcomes.

Magnetic resonance imaging of the failed superior capsular reconstruction.

Background: Superior capsular reconstruction (SCR) of the shoulder is an increasingly common procedure in the treatment of patients with massive, irreparable rotator cuff tears lacking significant osteoarthritis. Post-operatively, the appearance of failed grafts has only been described in isolated case reports and review articles.

Methods: From January 2016 through December 2017, surgical records at a single tertiary-care facility were queried to identify all patients undergoing SCR.

Reducing Core Stability Influences Lower Extremity Biomechanics in Novice Runners.

Purpose: The role of core stability in running and its influence on injury risk in runners is not well understood. The purpose of this study was to investigate the effect of core stability (and core fatigue) on running mechanics. We hypothesized that decreasing core stability in novice runners would result in altered running mechanics previously associated with increased risk for common lower extremity running injuries.