Rheumatoid Synovial Fluid and Acidic Extracellular pH Modulate the Immunomodulatory Activity of Urine-Derived Stem Cells.

Urine-derived stem cells (UdSCs) possess a remarkable anti-inflammatory and immune-modulating activity. However, the clinical significance of UdSCs in autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is yet to be explored. Hence, we tested the UdSCs response to an articular RA microenvironment. To simulate the inflamed RA joint more authentically in vitro, we treated cells with rheumatoid synovial fluids (RASFs) collected from RA patients, serum deprivation, acidosis (pH 7.0 and 6.5), and their combinations. Firstly, the RASFs pro-inflammatory status was assessed by cytokine quantification. Then, UdSCs were exposed to the RA environmental factors for 48 h and cell proliferation, gene expression and secretion of immunomodulatory factors were evaluated. The immunosuppressive potential of pre-conditioned UdSCs was also assessed via co-cultivation with activated peripheral blood mononuclear cells (PBMCs). In all experimental conditions, UdSCs' proliferation was not affected. Conversely, extracellular acidosis considerably impaired the viability/proliferation of adipose tissue-derived stem cells (ATSCs). In the majority of cases, exposure to RA components led to the upregulated expression of IL-6, TSG6, ICAM-1, VCAM-1, and PD-L1, all involved in immunomodulation. Upon RASFs and acidic stimulation, UdSCs secreted higher levels of immunomodulatory cytokines: IL-6, IL-8, MCP-1, RANTES, GM-CSF, and IL-4. Furthermore, RASFs and combined pretreatment with RASFs and acidosis promoted the UdSCs-mediated immunosuppression and the proliferation of activated PBMCs was significantly inhibited. Altogether, our data indicate that the RA microenvironment certainly has the capacity to enhance UdSCs' immunomodulatory function. For potential preclinical/clinical applications, the intra-articular injection might be a reasonable approach to maximize UdSCs' therapeutic efficiency in the RA treatment.

Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review.

This article provides a thorough overview of the available resorbable biomaterials appropriate for producing replacements for damaged tissues. In addition, their various properties and application possibilities are discussed as well. Biomaterials are fundamental components in tissue engineering (TE) of scaffolds and play a critical role. They need to exhibit biocompatibility, bioactivity, biodegradability, and non-toxicity, to ensure their ability to function effectively with an appropriate host response. With ongoing research and advancements in biomaterials for medical implants, the objective of this review is to explore recently developed implantable scaffold materials for various tissues. The categorization of biomaterials in this paper includes fossil-based materials (e.g., PCL, PVA, PU, PEG, and PPF), natural or bio-based materials (e.g., HA, PLA, PHB, PHBV, chitosan, fibrin, collagen, starch, and hydrogels), and hybrid biomaterials (e.g., PCL/PLA, PCL/PEG, PLA/PEG, PLA/PHB PCL/collagen, PCL/chitosan, PCL/starch, and PLA/bioceramics). The application of these biomaterials in both hard and soft TE is considered, with a particular focus on their physicochemical, mechanical, and biological properties. Furthermore, the interactions between scaffolds and the host immune system in the context of scaffold-driven tissue regeneration are discussed. Additionally, the article briefly mentions the concept of in situ TE, which leverages the self-renewal capacities of affected tissues and highlights the crucial role played by biopolymer-based scaffolds in this strategy.

Mesenchymal-Stromal-Cell-Conditioned Media and Their Implication for Osteochondral Regeneration.

Despite significant advances in biomedical research, osteochondral defects resulting from injury, an autoimmune condition, cancer, or other pathological conditions still represent a significant medical problem. Even though there are several conservative and surgical treatment approaches, in many cases, they do not bring the expected results and further permanent damage to the cartilage and bones occurs. Recently, cell-based therapies and tissue engineering have gradually become promising alternatives. They combine the use of different types of cells and biomaterials to induce regeneration processes or replace damaged osteochondral tissue. One of the main challenges of this approach before clinical translation is the large-scale in vitro expansion of cells without changing their biological properties, while the use of conditioned media which contains various bioactive molecules appears to be very important. The presented manuscript provides a review of the experiments focused on osteochondral regeneration by using conditioned media. In particular, the effect on angiogenesis, tissue healing, paracrine signaling, and enhancing the properties of advanced materials are pointed out.

Implication of Mesenchymal Stem Cells and Their Derivates for Osteochondral Regeneration.

Healing of articular cartilage defects presents a challenging issue, due to its regenerative shortcomings. Lacking vascularity and innervation of cartilage and low proliferative potential of chondrocytes are the main reasons for the limited healing potential of articular cartilage. Traditional reparative approaches are limited in their efficiency, hence there is a demand for novel reparative treatments. Mesenchymal stromal cells, preferred for clinical uses, can be readily derived from various sources and have been proven to have a therapeutic effect on cartilage and subchondral bone. Therefore, mesenchymal stromal cells, their derivates, and scaffolds have been utilized in research targeting osteochondral regeneration. The present review aims to comprehensively outline and discuss literature considering this topic published within last 5 years.

Rheumatoid arthritis: From synovium biology to cell-based therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial joints and, if not treated properly, can lead to multiple progressive articular and extra-articular damage. Its pathogenesis is primarily associated with an inadequate immune response and dysregulated cytokine production. However, RA is also linked to disruption in oxygen metabolism, impaired redox signaling, acidosis and aberrant intercellular communication. Even though treatment modalities have made RA a manageable disease, a significant number of patients still do not respond satisfactorily or suffer considerably from the adverse events of conventional therapy. In recent years, cell-based strategies, especially the administration of the mesenchymal/medicinal stem/signaling cells (MSCs), have been proposed as a novel and very promising therapeutic approach. RA patients may benefit from the potent anti-inflammatory and immunomodulatory properties and tissue-repair potential of MSCs. Furthermore, the satisfactory safety profile of MSC therapy has been already demonstrated in several clinical studies. This review summarizes current understanding of the pathomechanism behind RA at the molecular and cellular level and focuses on MSC-based clinical research and applications of MSCs for RA treatment.

Tissue Engineering of the Urethra: From Bench to Bedside.

Tissue engineering (TE) is a promising approach for repair/substitution of damaged tissues and organs. Urethral strictures are common and serious health conditions that impair quality of life and may lead to serious organ damage. The search for ideal materials for urethral repair has led to interest of scientists and surgeons in urethral TE. Over the last decades, a significant amount of preclinical studies and considerable progress have been observed. In contrast, urethral TE has made slow progress in clinical practice so far. To address this, we conducted a systematic review of the literature on clinical applications of TE constructs for urethral repair in the last three decades. In summary, the TE approach is promising and effective, but many issues remain that need to be addressed for broader adoption of TE in urethral repair. Better design of trials, better cooperation of research groups and centralization could lead to reduction of costs and slowly proceed to commercialization and routine use of TE products for urethral reconstruction.

Isolation, Culture and Comprehensive Characterization of Biological Properties of Human Urine-Derived Stem Cells.

Mesenchymal stem cells (MSCs) represent an attractive source within the field of tissue engineering. However, their harvesting often requires invasive medical procedures. Urine-derived stem cells (UDSCs) display similar properties to MSCs, and their obtention and further processing is non-invasive for the donors as well as low cost. Here, we offer a comprehensive analysis of their biological properties. The goal of this study was to analyze their morphology, stemness, differentiation potential and cytokine profile. We have successfully isolated UDSCs from 25 urine samples. First colonies emerged up to 9 days after the initial seeding. Cell doubling time was 45 ± 0.24 SD, and when seeded at the density of 100 cells/cm2, they formed 42 ± 6.5 SD colonies within 10 days. Morphological analyzes revealed that two different types of the cell populations have been present. The first type had a rice-grain shape and the second one was characterized by a polyhedral shape. In several cell cultures, dome-shaped cells were observed as well. All examined UDSCs expressed typical MSC-like surface markers, CD73, CD90 and CD105. Moreover, conditioned media from UDSCs were harvested, and cytokine profile has been evaluated showing a significantly higher secretory rate of IL-8, IL-6 and chemokines MCP-1 and GM-CSF. We have also successfully induced human UDSCs into chondrogenic, osteogenic and myogenic cell lineages. Our findings indicate that UDSCs might have immense potential in the regeneration of the damaged tissues.

In Vitro Characterization of Poly(Lactic Acid)/ Poly(Hydroxybutyrate)/ Thermoplastic Starch Blends for Tissue Engineering Application.

Complex in vitro characterization of a blended material based on Poly(Lactic Acid), Poly(Hydroxybutyrate), and Thermoplastic Starch (PLA/PHB/TPS) was performed in order to evaluate its potential for application in the field of tissue engineering. We focused on the biological behavior of the material as well as its mechanical and morphological properties. We also focused on the potential of the blend to be processed by the 3D printer which would allow the fabrication of the custom-made scaffold. Several blends recipes were prepared and characterized. This material was then studied in the context of scaffold fabrication. Scaffold porosity, wettability, and cell-scaffold interaction were evaluated as well. MTT test and the direct contact cytotoxicity test were applied in order to evaluate the toxic potential of the blended material. Biocompatibility studies were performed on the human chondrocytes. According to our results, we assume that material had no toxic effect on the cell culture and therefore could be considered as biocompatible. Moreover, PLA/PHB/TPS blend is applicable for 3D printing. Printed scaffolds had highly porous morphology and were able to absorb water as well. In addition, cells could adhere and proliferate on the scaffold surface. We conclude that this blend has potential for scaffold engineering.

Bioengineered Scaffolds as Substitutes for Grafts for Urethra Reconstruction.

Urethral defects originating from congenital malformations, trauma, inflammation or carcinoma still pose a great challenge to modern urology. Recent therapies have failed many times and have not provided the expected results. This negatively affects patients' quality of life. By combining cells, bioactive molecules, and biomaterials, tissue engineering can provide promising treatment options. This review focused on scaffold systems for urethra reconstruction. We also discussed different technologies, such as electrospinning and 3D bioprinting which provide great possibility for the preparation of a hollow structure with well-defined architecture.

Cells Involved in Urethral Tissue Engineering: Systematic Review.

The urethra is part of the lower urinary tract and its main role is urine voiding. Its complex histological structure makes urethral tissue prone to various injuries with complicated healing processes that often lead to scar formation. Urethral stricture disease can affect both men and women. The occurrence of this pathology is more common in men and thus are previous research has been mainly oriented on male urethra reconstruction. However, commonly used surgical techniques show unsatisfactory results because of complications. The new and progressively developing field of tissue engineering offers promising solutions, which could be applied in the urethral regeneration of both men´s and women´s urethras. The presented systematic review article offers an overview of the cells that have been used in urethral tissue engineering so far. Urine-derived stem cells show a great perspective in respect to urethral tissue engineering. They can be easily harvested and are a promising autologous cell source for the needs of tissue engineering techniques. The presented review also shows the importance of mechanical stimuli application on maturating tissue. Sufficient vascularization and elimination of stricture formation present the biggest challenges not only in customary surgical management but also in tissue-engineering approaches.

Induced Pluripotent Stem Cells for Duchenne Muscular Dystrophy Modeling and Therapy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, caused by mutation of the DMD gene which encodes the protein dystrophin. This dystrophin defect leads to the progressive degeneration of skeletal and cardiac muscles. Currently, there is no effective therapy for this disorder. However, the technology of cell reprogramming, with subsequent controlled differentiation to skeletal muscle cells or cardiomyocytes, may provide a unique tool for the study, modeling, and treatment of Duchenne muscular dystrophy. In the present review, we describe current methods of induced pluripotent stem cell generation and discuss their implications for the study, modeling, and development of cell-based therapies for Duchenne muscular dystrophy.