White Papers and Research

Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications

Wharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose.

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Wharton's Jelly The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells. (MSC)

The umbilical cord has become an increasingly used source of mesenchymal stromal cells for preclinical and, more recently, clinical studies. Despite the increased activity, several aspects of this cell population have been under-appreciated.

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Umbilical Cord Tissue for Research and Clinical Application

Variations in allogeneic mesenchymal stem cell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present,Wharton’s jelly tissue yields the highest concentration of allogeneic mesenchymal stem cells.

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Effect of Aging on Stem Cells

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered.

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Consequences of Telomere Shortening During Lifespan

Telomerase expression is restricted in human cells and so telomeres shorten throughout our lives, providing a tumor suppressor mechanism that limits cell proliferation. As a trade-off, continuous telomere erosion results in replicative senescence and contributes to aging.

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Mesenchymal Stem Cells: Mechanisms of Inflammation

In adults, human mesenchymal stem cells (hMSCs) are found in vivo at low frequency and are defined by their capacity to differentiate into bone, cartilage, and adipose tissue, depending on the stimuli and culture conditions under which they are expanded. Although MSCs were initially hypothesized to be the panacea for regenerating tissues, MSCs appear to be more important in therapeutics to regulate the immune response invoked in settings such as tissue injury, transplantation, and autoimmunity.

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Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine

The amniotic membrane (AM) and amniotic fluid (AF) have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine.

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Minimal criteria for defining multipotent mesenchymal stromal cells.

The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field.

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Cytokines, Inflammation and Pain

Cytokines are small secreted proteins released by cells have a specific effect on the interactions and communications between cells. Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes).

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Intramuscular administration potentiates extended dwell time of mesenchymal stromal cells compared to other routes

Mesenchymal stromal cells (MSCs) offer great potential for diverse clinical applications. However, conventional systemic infusion of MSCs limits their therapeutic benefit, since intravenously (IV) infused cells become entrapped in the lungs where their dwell time is short. Methods. To explore possible alternatives to IV infusion, we used in vivo optical imaging to track the bio-distribution and survival of 1 million bioluminescent MSCs administered IV, intraperitoneally (IP), subcutaneously (SC) and intramuscularly (IM) in healthy athymic mice

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Cytotoxicity of Local Anesthetics on Human Mesenchymal Stem Cells

Local anesthetics are frequently delivered intra-articularly to provide perioperative pain control. Previous studies have shown that the commonly used drugs lidocaine, ropivacaine, and bupivacaine can be toxic to human chondrocytes. The present study was conducted to determine whether the toxic effects of local anesthetics on human chondrocytes also extend to human mesenchymal stem cells.

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Mesenchymal stem cells and immunomodulation: current status and future prospects

The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them an invaluable cell type for the repair of tissue/ organ damage caused by chronic inflammation or autoimmune disorders. Although they hold great promise in the treatment of immune disorders such as graft versus host disease (GvHD) and allergic disorders, there remain many challenges to overcome before their widespread clinical application.

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Knee Cartilage Regeneration with Umbilical Cord Mesenchymal Stem Cells Embedded in Collagen Scaffold Using Dry Arthroscopy Technique

Mesenchymal stem cells (MSC) provide an interesting new option in regenerative medicine with solid preclinical data and first promising clinical results. They act not only through direct cartilage formation, but also due to paracrine effects, such as releasing trophic factors, antiinflammatory cytokines, and promoting angiogenesis.

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Pulmonary Passage is a Major Obstacle for Intravenous Stem Cell Delivery: The Pulmonary First-Pass Effect

Intravenous (IV) stem cell delivery for regenerative tissue therapy has been increasingly used in both experimental and clinical trials. However, recent data suggest that the majority of administered stem cells are initially trapped in the lungs. We sought to investigate variables that may affect this pulmonary fi rst-pass effect.

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Multipotent Stem Cells from Umbilical Cord: Cord Is Richer than Blood!

The identification of mesenchymal stem cell (MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. Here, we compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors.

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Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial

Despite advances in early diagnosis and behavioral therapies, more effective treatments for children with autism spectrum disorder (ASD) are needed.We hypothesized that umbilical cord blood derived cell therapies may have potential in alleviating ASD symptoms by modulating inflammatory processes in the brain. Accordingly, we conducted a phase I, open-label trial to assess the safety and feasibility of a single intravenous infusion of autologous umbilical cord blood, as well as sensitivity to change in several ASD assessment tools, to determine suitable endpoints for future trials.

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The life and fate of mesenchymal stem cells

Mesenchymal stem cells (MSC) are present throughout the body and are thought to play a role in tissue regeneration and control of inflammation. MSC can be easily expanded in vitro and their potential as a therapeutic option for degenerative and inflammatory disease is therefore intensively investigated. Whilst it was initially thought that MSC would replace dysfunctional cells and migrate to sites of injury to interact with inflammatory cells, experimental evidence indicates that the majority of administered MSC get trapped in capillary networks and have a short lifespan.

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Potency of umbilical cord bloodand Wharton’s jelly-derived mesenchymal stem cells for scarless wound healing

Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCBMSCs) and Wharton’s jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections.

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Umbilical cord mesenchymal stromal cell transplantations: A systemic analysis of clinical trials

The advances and success of umbilical cord–derived mesenchymal stromal cells (UC-MSCs) in experimental disease animal models have fueled the development of targeted therapies in humans. The therapeutic potential of allogeneic transplantation of UC-MSCs has been under examination since 2009. The purpose of this systematic analysis was to review the published results, limitations and obstacles for UC-MSC transplantation

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Inflammation and wound healing: The role of the macrophage

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes.

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Mesenchymal Stem Cells as Trophic Mediators

Adult marrow-derived Mesenchymal Stem Cells (MSCs) are capable of dividing and their progeny are further capable of differentiating into one of several mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, and adipocytes. In addition, these MSCs secrete a variety of cytokines and growth factors that have both paracrine and autocrine activities. These secreted bioactive factors suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate mitosis and differentiation of tissue-intrinsic reparative or stem cells.

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Fetuin A

A liver-derived protein, fetuin-A, was first purified from calf fetal serum in 1944, but its potential role in lethal systemic inflammation was previously unknown. This study aims to delineate the molecular mechanisms underlying the regulation of hepatic fetuin-A expression during lethal systemic inflammation (LSI), and investigated whether alterations of fetuin-A levels affect animal survival, and influence systemic accumulation of a late mediator, HMGBl

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Interleukin 37

Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1b production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1b secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.

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Serpin A4

In all Kallistatin (serpin A4) treated rats, activation of hepatic stellate cells (HSC) as assessed by s-smooth muscle actin staining was attenuated, TGF-B1 expression was inhibited, class 1 serum biomarkers associated with the process of fibrogenesis, such as hyaluronic acid, laminin and procollagen III, were lowered, compared with that in the model control group.

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Synedecan-4

Skeletal muscle satellite cells, located between the basal lamina and plasma membrane of myofibers, are required for skeletal muscle regeneration. The capacity of satellite cells, as well as other cell lineages including mesoangioblasts, mesenchymal stem cells, and side population (SP) cells to contribute to muscle regeneration, has complicated the identification of a satellite stem cell. We have characterized a rare subset of the muscle SP that efficiently engrafts into the host satellite cell niche when transplanted into regenerating muscle, providing 75% of the satellite cell population and 30% of the myonuclear population, respectively. These cells are found in the satellite cell position, adhere to isolated myofibers, and spontaneously undergo myogenesis in culture. We propose that this subset of SP cells (satellite-SP cells), characterized by ABCG2, Syndecan-4, and Pax? expression, constitutes a self-renewing muscle stem cell capable of generating both satellite cells and their myonuclear progeny in vivo.

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BMP-7

Degenerative discs can cause low back pain. Cell-based transplantation or growth factors therapy have been suggested as a strategy to stimulate disc regeneration. Bone marrow-derived mesenchymal stem cells (BMDMSC) containing bone morphogenetic protein-7 (BMP-7) gene were constructed.

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Complement C5A

The complement and neutrophil defense systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis.

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