Phenolated alginate hydrogel induced osteogenic properties of mesenchymal stem cells via Wnt signaling pathway.

Osteogenic properties of phenolated alginate (1.2 %) hydrogel containing collagen (0.5 %)/nano-hydroxyapatite (1 %) were studied on human mesenchymal stem cells in vitro. The phenolation rate and physical properties of the hydrogel were assessed using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), swelling ratio, gelation time, mechanical assay, and degradation rate. The viability of encapsulated cells was monitored on days 7, 14, and 21 using an MTT assay. Osteoblast differentiation was studied using western blotting, and real-time PCR. Using PCR array analysis, the role of the Wnt signaling pathway was also investigated. Data showed that the combination of alginate/collagen/nanohydroxyapatite yielded proper mechanical features. The addition of nanohydroxyapatite, and collagen reduced degradation, swelling rate coincided with increased stiffness. Elasticity and pore size were also diminished. NMR and FTIR revealed suitable incorporation of collagen and nanohydroxyapatite in the structure of alginate. Real-time PCR analysis and western blotting indicated the expression of osteoblast-related genes such as Runx2 and osteocalcin. PCR array revealed the induction of numerous genes related to Wnt signaling pathways during the maturation of human stem cells toward osteoblast-like cells. In vivo data indicated that transplantation of phenolated alginate/collagen/nanohydroxyapatite hydrogel led to enhanced de novo bone formation in rats with critical-sized calvarial defects. Phenolated alginate hydrogel can promote the osteogenic capacity of human amniotic membrane mesenchymal stem cells in the presence of nanohydroxyapatite and collagen via engaging the Wnt signaling pathway.

Application of mesenchymal stem cell sheet for regeneration of craniomaxillofacial bone defects.

Bone defects are among the most common damages in human medicine. Due to limitations and challenges in the area of bone healing, the research field has turned into a hot topic discipline with direct clinical outcomes. Among several available modalities, scaffold-free cell sheet technology has opened novel avenues to yield efficient osteogenesis. It is suggested that the intact matrix secreted from cells can provide a unique microenvironment for the acceleration of osteoangiogenesis. To the best of our knowledge, cell sheet technology (CST) has been investigated in terms of several skeletal defects with promising outcomes. Here, we highlighted some recent advances associated with the application of CST for the recovery of craniomaxillofacial (CMF) in various preclinical settings. The regenerative properties of both single-layer and multilayer CST were assessed regarding fabrication methods and applications. It has been indicated that different forms of cell sheets are available for CMF engineering like those used for other hard tissues. By tackling current challenges, CST is touted as an effective and alternative therapeutic option for CMF bone regeneration.

A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds.

Certain polymeric materials such as polyurethanes (PUs) are the most prevalent class of used biomaterials in regenerative medicine and have been widely explored as vascular substitutes in several animal models. It is thought that PU-based biomaterials possess suitable hemo-compatibility with comparable performance related to the normal blood vessels. Despite these advantages, the possibility of thrombus formation and restenosis limits their application as artificial functional vessels. In this regard, various surface modification approaches have been developed to enhance both hemo-compatibility and prolong patency. While critically reviewing the recent advances in vascular tissue engineering, mainly PU grafts, this paper summarizes the application of preferred cell sources to vascular regeneration, physicochemical properties, and some possible degradation mechanisms of PU to provide a more extensive perspective for future research.

The efficiency of PCL/HAp electrospun nanofibers in bone regeneration: a review.

Electrospinning is a method which produces various nanofiber scaffolds for different tissues was attractive for researchers. Nanofiber scaffolds could be made from several biomaterials and polymers. Quality and virtues of final scaffolds depend on used biomaterials (even about single substance, the origin is effective), additives (such as some molecules, ions, drugs, and inorganic materials), electrospinning parameter (voltage, injection speed, temperature, …), etc. In addition to its benefits, which makes it more attractive is the possibility of modifications. Common biomaterials in bone tissue engineering such as poly-caprolactone (PCL), hydroxyapatite (HAp), and their important features, electrospinning nanofibers were widely studied. Related investigations indicate the critical role of even small parameters (like the concentration of PCL or HAp) in final product properties. These changes also, cause deference in cell proliferation, adhesion, differentiation, and in vivo repair process. In this review was focussed on PCL/HAp based nanofibers and additives that researchers used for scaffold improvement. Then, reviewing properties of gained nanofibers, their effect on cell behaviour, and finally, their valency in bone tissue engineering studies (in vitro and in vivo).

Efficacy of mesenchymal stromal cells and cellular products in improvement of symptoms for COVID-19 and similar lung diseases.

At the end of 2019, respiratory coronavirus diseases 2019 (COVID-19) appeared and spread rapidly in the world. Besides several mutations, the outcome of this pandemic was the death up to 15% of hospitalized patients. Mesenchymal stromal cell therapy as a therapeutic strategy seemed successful in treatment of several diseases. Not only mesenchymal stromal cells of several tissues, but also their secreted extracellular vesicles and even secretome indicated beneficial therapeutic function. All of these three options were studied for treatment of COVID-19 as well as those respiratory diseases that have similar symptom. Fortunately, most of the outcomes were promising and optimistic. In this paper, we review in-vivo and clinical studies which have been used different sources of mesenchymal stromal cell, secreted extracellular vesicles, and secretome to improve and treat symptoms of COVID-19 and similar lung diseases.

DNA damage repair response in mesenchymal stromal cells: From cellular senescence and aging to apoptosis and differentiation ability.

Mesenchymal stromal cells (MSCs) are heterogeneous and contain several populations, including stem cells. MSCs' secretome has the ability to induce proliferation, differentiation, chemo-attraction, anti-apoptosis, and immunomodulation activities in stem cells. Moreover, these cells recognize tissue damage caused by drugs, radiation (e.g., Ultraviolet, infra-red) and oxidative stress, and respond in two ways: either MSCs differentiate into particular cell lineages to preserve tissue homeostasis, or they release a regenerative secretome to activate tissue repairing mechanisms. The maintenance of MSCs in quiescence can increase the incidence and accumulation of various forms of genomic modifications, particularly upon environmental insults. Thus, dysregulated DNA repair pathways can predispose MSCs to senescence or apoptosis, reducing their stemness and self-renewal properties. For instance, DNA damage can impair telomere replication, activating DNA damage checkpoints to maintain MSC function. In this review, we aim to summarize the role of DNA damage and associated repair responses in MSC senescence, differentiation and programmed cell death.

Combination of nanotechnology with vascular targeting agents for effective cancer therapy.

As a young science, nanotechnology promptly integrated into the current oncology practice. Accordingly, various nanostructure particles were developed to reduce drug toxicity and allow the targeted delivery of various diagnostic and therapeutic compounds to the cancer cells. New sophisticated nanosystems constantly emerge to improve the performance of current anticancer modalities. Targeting tumor vasculature is an attractive strategy to fight cancer. Though the idea was swiftly furthered from basic science to the clinic, targeting tumor vasculature had a limited potential in patients, where tumors relapse due to the development of multiple drug resistance and metastasis. The aim of this review is to discuss the advantages of nanosystem incorporation with various vascular targeting agents, including (i) endogen anti-angiogenic agents; (ii) inhibitors of angiogenesis-related growth factors; (iii) inhibitors of tyrosine kinase receptors; (iv) inhibitors of angiogenesis-related signaling pathways; (v) inhibitors of tumor endothelial cell-associated markers; and (vi) tumor vascular disrupting agents. We also review the efficacy of nanostructures as natural vascular targeting agents. The efficacy of each approach in cancer therapy is further discussed.