scholarly journals Ανοσοϊστοχημική, απεικονιστική και εμβιομηχανική μελέτη βιολογικών φαινομένων σε πειραματικό μοντέλο διαταραχών πωρώσεως

2013 ◽  
Author(s):  
Χριστόφορος Τζιούπης
Keyword(s):  
Growth Factors ◽  
Stromal Cells ◽  
Regenerative Process ◽  
X Rays ◽  
Safe Alternative ◽  
Promising Alternative ◽  
Biomimetic Scaffolds ◽  
Ulna Osteotomy ◽  
Biomimetic Scaffold ◽  
Synthetic Scaffolds

Background: Fracture healing is a complex, well-orchestrated regenerative process, initiated in response to injury, resulting in optimal skeletal repair and restoration of skeletal function. Despite the progress accomplished towards the treatment of fractures in recent years, impaired healing in terms of delayed union and nonunion are still one of the most severe local complications, as they require a lengthy treatment. Most importantly, they represent a chronic clinical condition, which is difficult for patients to endure. Despite the effectiveness of treatments applied so far, no method has proven its efficacy regarding its reproducibility and cost justification. In this context, the field of Bone Tissue Engineering emerges as a promising alternative, accumulating and implementing knowledge from various disciplines and aiming at bone regeneration by use of biomimetic materials, growth factors and mesenchymal cells.Objective: The aim of this study was to investigate the efficacy of the implementation of biomimetic, naturally-derived and synthetic scaffolds alone or in combination with autologous growth factors and bone marrow stromal cells in terms of their ability to heal critical-size defects.Materials and Methods: Forty-eight NWZ rabbits weighing 2.9 to 3.5 kg were used for the purposes of the present study. An ulna osteotomy (15mm) was performed and the void was filled with naturally-derived and synthetic scaffolds alone or in combination with PRP and BMSCs. Imaging assessment of the regenerative process was made by use of x-rays at 4 and 8 weeks, as well as with CT and micro-CT at 8 weeks. After this time, all animals were sacrificed. Subsequently, the test samples were subjected to histological, imaging and biomechanical assessment.Results: All animals survived until the end of the study. No complications were encountered. The implemented scaffolds proved highly biocompatible and exerted a high degree of bone regenerative capacity, especially when they were seeded with growth factors and mesenchymal stem cells. Histological assessment revealed the existence of mature lamellar bone in all groups, with statistically significant superiority of those groups in which PRP and BMSCs were used concomitantly. Based on the 3D-histomorphometry, the synthetic biomimetic scaffold yielded superior results either alone or in combination with PRP and BMSCs.Conclusions: The implementation of biomimetic scaffolds is a safe alternative therapeutic approach in the treatment of nonunions. The seeding of biomimetic scaffolds with growth factors and stromal cells enhances their bone regenerative quantitative and the qualitative properties. The synthetic biomimetic scaffold used has proven superior, as compared to the naturally-derived one. This “on-site” strategy is safe, minimally invasive, and could be easily translated into the clinical field.

scholarly journals Combinations of Hydrogels and Mesenchymal Stromal Cells (MSCs) for Cartilage Tissue Engineering—A Review of the Literature

Gels ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 217
Author(s):  
Mike Wagenbrenner ◽  
Susanne Mayer-Wagner ◽  
Maximilian Rudert ◽  
Boris Michael Holzapfel ◽  
Manuel Weissenberger
Keyword(s):  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Promising Alternative ◽  
Advantages And Disadvantages ◽  
Cartilage Engineering ◽  
Or Gene

Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration

2016 ◽  
Vol 17 (2) ◽  
pp. 197-212 ◽  
Author(s):  
Mikel Sánchez ◽  
Eduardo Anitua ◽  
Diego Delgado ◽  
Peio Sanchez ◽  
Roberto Prado ◽  
...  
Keyword(s):  
Growth Factors ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Platelet Rich Plasma ◽  
Peripheral Nerve Regeneration ◽  
Biomimetic Scaffold

scholarly journals The Role of Porphyrinoid Photosensitizers for Skin Wound Healing

2021 ◽  
Vol 22 (8) ◽  
pp. 4121
Author(s):  
Mariana C. S. Vallejo ◽  
Nuno M. M. Moura ◽  
Ana T. P. C. Gomes ◽  
Ana S. M. Joaquinito ◽  
Maria Amparo F. Faustino ◽  
...  
Keyword(s):  
Wound Healing ◽  
Aminolevulinic Acid ◽  
Healing Process ◽  
Protoporphyrin Ix ◽  
Skin Wound ◽  
Regenerative Process ◽  
Inflammatory Factors ◽  
Skin Wound Healing ◽  
Promising Alternative ◽  
Bacteria And Fungi

Microorganisms, usually bacteria and fungi, grow and spread in skin wounds, causing infections. These infections trigger the immune system and cause inflammation and tissue damage within the skin or wound, slowing down the healing process. The use of photodynamic therapy (PDT) to eradicate microorganisms has been regarded as a promising alternative to anti-infective therapies, such as those based on antibiotics, and more recently, is being considered for skin wound-healing, namely for infected wounds. Among the several molecules exploited as photosensitizers (PS), porphyrinoids exhibit suitable features for achieving those goals efficiently. The capability that these macrocycles display to generate reactive oxygen species (ROS) gives a significant contribution to the regenerative process. ROS are responsible for avoiding the development of infections by inactivating microorganisms such as bacteria but also by promoting cell proliferation through the activation of stem cells which regulates inflammatory factors and collagen remodeling. The PS can act solo or combined with several materials, such as polymers, hydrogels, nanotubes, or metal-organic frameworks (MOF), keeping both the microbial photoinactivation and healing/regenerative processes’ effectiveness. This review highlights the developments on the combination of PDT approach and skin wound healing using natural and synthetic porphyrinoids, such as porphyrins, chlorins and phthalocyanines, as PS, as well as the prodrug 5-aminolevulinic acid (5-ALA), the natural precursor of protoporphyrin-IX (PP-IX).

scholarly journals Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

2012 ◽  
Vol 214 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Linda Vignozzi ◽  
Ilaria Cellai ◽  
Raffaella Santi ◽  
Letizia Lombardelli ◽  
Annamaria Morelli ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Receptor Activation ◽  
Prostatic Hyperplasia ◽  
Serum Testosterone Level ◽  
Antiinflammatory Effect ◽  
Inflammatory Growth

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4+T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4+T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

scholarly journals The First Allogeneic Transplantation of Human Umbilical Cord-derived Mesenchymal Stem/stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants

2020 ◽  
Author(s):  
Liem Nguyen Thanh ◽  
Thai Trieu Thi Hong ◽  
Hue Bui Thi Hong ◽  
Van T. Hoang ◽  
Anh Nguyen Thi Tuyet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Umbilical Cord ◽  
Bronchopulmonary Dysplasia ◽  
Stromal Cells ◽  
Perinatal Care ◽  
Allogeneic Transplantation ◽  
Human Umbilical Cord ◽  
X Rays ◽  
Severe Condition

Abstract Background: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises theirlung function and necessitatesoxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety ofthe allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the preliminary efficacy of the treatment in four infants with established BPD.Methods: UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno-free and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and efficacy were evaluated during hospitalization and at 7 days and 1, 6 and 12 postdischargemonths.Results: No transplantation-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and been weaned off of oxygen support. Chest X-rays and CT scans confirmed the dramatic reduction infibrosis.Conclusions: Allo-UC-MSC transplantation is safe and might improve respiratory function anddecrease lung fibrosis in preterm infants with established BPD.Trial registration: This preliminary study was approved by Vinmec International Hospital Ethics Board, approval number: 88/2019/QĐ-VMEC, registered 12 March 2019 - retrospectively registered.

Mineralized Nanofibers for Bone Tissue Engineering

2018 ◽  
pp. 461-475 ◽  
Author(s):  
Ozan Karaman
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Bone Grafts ◽  
Tissue Engineering Scaffolds ◽  
Promising Alternative ◽  
Biomimetic Scaffolds

The limitation of orthopedic fractures and large bone defects treatments has brought the focus on fabricating bone grafts that could enhance ostegenesis and vascularization in-vitro. Developing biomimetic materials such as mineralized nanofibers that can provide three-dimensional templates of the natural bone extracellular-matrix is one of the most promising alternative for bone regeneration. Understanding the interactions between the structure of the scaffolds and cells and therefore the control cellular pathways are critical for developing functional bone grafts. In order to enhance bone regeneration, the engineered scaffold needs to mimic the characteristics of composite bone ECM. This chapter reviews the fabrication of and fabrication techniques for fabricating biomimetic bone tissue engineering scaffolds. In addition, the chapter covers design criteria for developing the scaffolds and examples of enhanced osteogenic differentiation outcomes by fabricating biomimetic scaffolds.

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