Biological Macromolecule-Based Scaffolds for Urethra Reconstruction.

Urethral reconstruction strategies are limited with many associated drawbacks. In this context, the main challenge is the unavailability of a suitable tissue that can endure urine exposure. However, most of the used tissues in clinical practices are non-specialized grafts that finally fail to prevent urine leakage. Tissue engineering has offered novel solutions to address this dilemma. In this technology, scaffolding biomaterials characteristics are of prime importance. Biological macromolecules are naturally derived polymers that have been extensively studied for various tissue engineering applications. This review discusses the recent advances, applications, and challenges of biological macromolecule-based scaffolds in urethral reconstruction.

Bone mineral density status in patients with recent-onset rheumatoid arthritis.

Background: Osteoporosis is a sizable comorbidity complication in Rheumatoid Arthritis (RA) sufferers. In the current study, the prevalence of osteopenia and osteoporosis in active RA sufferers and the association of disease-related factors of osteoporosis and reduced bone mineral density (BMD) have been examined. Methods: In this cross-sectional study, 300 new-onset symptoms (less than one year) RA patients without a history of glucocorticoids or DMARDs were selected. Biochemical blood measurements and BMD status were performed with dual-energy X-ray absorptiometry. According to the T-scores of the patients, they were divided into three groups: osteoporosis<-2.5, -2.5 < osteopenia <-1, and - 1 < normal. Also, the MDHAQ questionnaire, DAS-28, and FRAX criteria were calculated for all patients. Multivariate logistic regression was used to determine the associated factors of osteoporosis and osteopenia. Results: The Prevalence of osteoporosis and osteopenia was 27% (95%CI:22-32) and 45% (95%CI:39-51), respectively. The multivariate regression analysis showed that age could play a role as an associated factor for spine/hip Osteoporosis and Osteopenia. The female gender is also a predictor of Spine osteopenia Patients with Total hip Osteoporosis were more likely to have higher DAS-28 (OR 1.86, CI 1.16-3.14) and positive CRP (OR 11.42, CI 2.65-63.26). Conclusion: recent-onset RA patients are at risk for osteoporosis and its complications, regardless of using glucocorticoids or DMARDs. Demographic factors (e.g. age and female gender), patients' MDHAQ scores, and disease-related factors(e.g., DAS-28, positive CRP were associated with reduced BMD levels. Therefore, it is recommended that clinicians investigate early BMD measurements to have a reasonable judgment for further interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01200-w.

Chitosan nanoparticles, as biological macromolecule-based drug delivery systems to improve the healing potential of artificial neural guidance channels: A review.

The healing potential of artificial neural guidance channels (NGCs) can be improved by various approaches such as seeding them with supporting cells, the incorporation of various cues, and modification with different fabrication methods. Recently, the therapeutic appeal towards the use of drug-delivering NGCs has increased. In this framework, neuroprotective agents are incorporated into the structure of NGCs using different techniques. Among available methods, nanoparticle-based drug carriers offer numerous advantages over other formulations such as controlled drug release, targeted delivery, high encapsulation efficacy, and high surface to volume ratio. Chitosan nanoparticles have different interesting features for drug delivery applications. These nanocarriers are biocompatible, biodegradable, non-immunogenic, stable, and possess tunable properties. In the current review, applications, challenges, and future perspectives of drug-loaded chitosan nanoparticles to augment the healing potential of NGCs will be discussed.

Endometrial mesenchymal stem/stromal cells: The Enigma to code messages for generation of functionally active regulatory T cells.

BACKGROUND: Regulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs. METHODS: MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with or without pre-treatment with mitomycin C, IFN-γ and IL-1ß was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-ß on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSCs culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry. RESULTS: According to the results, proliferation of T CD4 + lymphocytes was enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory cytokines reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased the frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1ß, they induced functional Tregs with ability to inhibit the proliferation of anti-CD3/CD28-stimulated PBMCs. This effect was mediated through IL-6, IL-10, TGF-ß and IDO. IFN-γ/IL-1ß-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells. CONCLUSION: Collectively, these findings indicate that immunomodulatory impact of menstrual blood stem cells (MenSCs) on generation of Tregs and inhibition of T cells proliferation is largely dependent on pre-treatment with IFN-γ and IL-1ß. This is the first report on immunomodulatory impact of MenSCs on Tregs and highlights the pivotal role of endometrial stem cells in regulation of local endometrial immune responses.

Human amniotic membrane as a delivery vehicle for stem cell-based therapies.

Stem cell-based therapy is known as a regenerative approach for a variety of diseases and tissue injuries. These cells exert their therapeutic effects through paracrine secretions namely extracellular vesicles. To achieve higher therapeutic potential, a variety of delivery routes have been tested in clinical and preclinical studies. Direct cell injection, intra-venous administration, and intra-arterial infusion are widely used methods of stem cells delivery but these methods are associated with several complications. As one of the most popular biological delivery systems, amniotic membrane has been widely utilized to support cell proliferation and differentiation therefore facilitating tissue regeneration without endangering the stem cells' viability. It is composed of several extracellular matrix components and growth factors. Due to these characteristics, amniotic membrane can mimic the stem cell's niche and can be an ideal carrier for stem cell transplantation. Here, we provide an overview of the recent progress, challenges, and future perspectives in the use of amniotic membrane as a delivery platform for stem cells.

MenSCs exert a supportive role in establishing a pregnancy-friendly microenvironment by inhibiting TH17 polarization.

OBJECTIVES: Uncontrolled TH17 differentiation has been suggested to play a role in the pathogenesis of pregnancy loss. We recently showed that menstrual blood stromal/stem cells (MenSCs) alter functional features of natural killer cells. Here, we hypothesized that MenSCs could modulate differentiation of TH17 cells. METHOD: MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. TH17 polarization and proliferation of purified T CD4+ cells were assessed by flow cytometry in a well-defined co-culture system containing T CD4+ cells and MenSCs or BMSCs. Indoleamine 2,3-Dioxygenase (IDO) activity was evaluated in MenSC and BMSC culture supernatants by a colorimetric assay. The impact of MenSCs on expression of transcription factors, RORC, T-bet, Gata3, NRP-1 and Helios were studied by qPCR. RESULTS: MenSCs significantly inhibited TH17 differentiation (p = 0.0383) and percentage of the cells co-expressing IL-17 and IFN-γ (p = 0.0023). PGE2 blockade significantly reduced percentage and proliferation of T CD4+IL-17+ (p = 0.003, p = 0.0018), T CD4+ IFN-γ+ (p = 0.002, p = 0.0022) and T CD4+IL-17+ IFN-γ+ (p = 0.004, p = 0.02) cells. MenSCs produced a considerable activity of IDO (p = 0.0002), induced a significant rise in the Treg frequency (p = 0.0091) and a sharp increase in TH17/Tregs ratio (p = 0.0022). MenSCs increased expression of NRP1 (p = 0.001), while downregulated expression of RORC in T cells (p = 0.001). CONCLUSION: Our results suggest a supportive role for MenSCs in establishing a pregnancy-friendly microenvironment in the uterus and put forth the idea that inherent abnormalities of MenSCs may be a basis for dysregulated endometrial immune network leading to pregnancy loss.

Human menstrual blood-derived stromal/stem cells modulate functional features of natural killer cells.

Although natural killer (NK) cells play a crucial role in the maintenance of a successful pregnancy, their cytotoxic activity should be tightly controlled. We hypothesized that endometrial mesenchymal stromal/stem cells (eMSCs) could potentially attenuate the functional features of NK cells. Herein, we assessed immunomodulatory effects of menstrual blood-derived stromal/stem cells (MenSCs), as a surrogate for eMSCs, on NK cells function. Our results showed that MenSCs induced proliferation of NK cells. However, IFN-γ/IL-1ß pretreated MenSCs significantly inhibited NK cell proliferation. Of 41 growth factors tested, MenSCs produced lower levels of insulin-like growth factor binding proteins (IGFBPs) 1-4, VEGF-A, ß-NGF, and M-CSF compared to bone marrow-derived mesenchymal stem cells (BMSCs). MenSCs displayed high activity of IDO upon IFN-γ treatment. The antiproliferative potential of IFN-γ/IL-1ß-pretreated MenSCs was mediated through IL-6 and TGF-ß. MenSCs impaired the cytotoxic activity of NK cells on K562 cells, consistent with the lower expression of perforin, granzymes A, and B. We also observed that in vitro decidualization of MenSCs in the presence of IFN-γ reduced the inhibitory effect of MenSCs on NK cell cytotoxicity against K562 target cells. Additionally, MenSCs were found to be prone to NK cell-mediated lysis in an MHC-independent manner. Our findings imply that dysregulation of NK cells in such pregnancy-related disorders as miscarriage may stem from dysfunctioning of eMSCs.

Menstrual Blood-Derived Stromal Stem Cells Augment CD4+ T Cells Proliferation.

BACKGROUND: It is more than sixty years that the concept of the fetal allograft and immunological paradox of pregnancy was proposed and in this context, several regulatory networks and mechanisms have been introduced so far. It is now generally recognized that mesenchymal stem cells exert potent immunoregulatory activity. In this study, for the first time, the potential impact of Menstrual blood Stem Cells (MenSCs), as surrogate for endometrial stem cells, on proliferative capacity of CD4+ T cells was tested. METHODS: MenSCs and Bone marrow Mesenchymal Stem Cells (BMSCs) were isolated and assessed for their immunophenotypic features and multi-lineage differentiation capability. BMSCs and MenSCs with or without IFNγ pre-stimulation were co-cultured with purified anti-CD3/CD28-activated CD4+ T cells and the extent of T cell proliferation at different MenSCs: T cell ratios were investigated by CSFE flow cytometry. IDO activity of both cell types was measured after stimulation with IFNγ by a colorimetric assay. RESULTS: MenSCs exhibited dual mesenchymal and embryonic markers and multi-lineage differentiation capacity. MenSCs significantly increased proliferation of CD4+ cells at ratios 1:2, 1:4 and 1:8. IFNγ pre-treated BMSCs but not MenSCs significantly suppressed CD4+ T cells proliferation. Such proliferation promoting capacity of MenSCs was not correlated with IDO activity as these cells showed the high IDO activity following IFNγ treatment. CONCLUSION: Although augmentation of T cell proliferation by MenSCs can be a basis for maintenance of endometrial homeostasis to cope with ascending infections, this may not fulfill the requirement for immunological tolerance to a semi-allogeneic fetus. However, more investigation is needed to examine whether or not the immunomodulatory properties of these cells are affected by endometrial microenvironment during pregnancy.

Promotion of excisional wound repair by a menstrual blood-derived stem cell-seeded decellularized human amniotic membrane.

This is the first study demonstrating the efficacy of menstrual blood-derived stem cell (MenSC) transplantation via decellularized human amniotic membrane (DAM), for the promotion of skin excisional wound repair. The DAM was seeded with MenSCs at the density of 3 × 104 cells/cm2 and implanted onto a rat's 1.50 × 1.50 cm2 full-thickness excisional wound defect. The results of wound closure and histopathological examinations demonstrated that the MenSC-seeded DAM could significantly improve the wound healing compared with DAM-treatment. All in all, our data indicated that the MenSCs can be a potential source for cell-based therapies to regenerate skin injuries.