The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide “off-the-shelf” cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient’s immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an “off-the-shelf” medical product.
The properties of mesenchymal stem cells (MSCs), especially their self-renewal and ability to differentiate into different cell lines, are widely discussed. Considering the fact that MSCs isolated from perinatal tissues reveal higher differentiation capacity than most adult MSCs, we examined mesenchymal stem cells isolated from Wharton’s jelly of umbilical cord (WJ-MSCs) in terms of pluripotency markers expression. Our studies showed that WJ-MSCs express some pluripotency markers—such as NANOG, OCT-4, and SSEA-4—but in comparison to iPS cells expression level is significantly lower. The level of expression can be raised under hypoxic conditions. Despite their high proliferation potential and ability to differentiate into different cells type, WJ-MSCs do not form tumors in vivo, the major caveat of iPS cells. Owing to their biological properties, high plasticity, proliferation capacity, and ease of isolation and culture, WJ-MSCs are turning out to be a promising tool of modern regenerative medicine.
Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3β activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies.
Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are multipotent stem cells that can be used in regenerative medicine. However, to reach the high therapeutic efficacy of WJ-MSCs, it is necessary to obtain a large amount of MSCs, which requires their extensive in vitro culturing. Numerous studies have shown that in vitro expansion of MSCs can lead to changes in cell behavior; cells lose their ability to proliferate, differentiate and migrate. One of the important measures of cells’ migration potential is their elasticity, determined by atomic force microscopy (AFM) and quantified by Young’s modulus. This work describes the elasticity of WJ-MSCs during in vitro cultivation. To identify the properties that enable transmigration, the deformability of WJ-MSCs that were able to migrate across the endothelial monolayer or Matrigel was analyzed by AFM. We showed that WJ-MSCs displayed differences in deformability during in vitro cultivation. This phenomenon seems to be strongly correlated with the organization of F-actin and reflects the changes characteristic for stem cell maturation. Furthermore, the results confirm the relationship between the deformability of WJ-MSCs and their migration potential and suggest the use of Young’s modulus as one of the measures of competency of MSCs with respect to their possible use in therapy.
In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality in regenerative medicine. They hold great promise for treating civilization-wide diseases, including cardiovascular diseases, such as acute myocardial infarction and critical limb ischemia. MSCs isolated from Wharton’s jelly (WJ-MSCs) may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits for patients. The efficacy of WJ-MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Ischemic limb disease is caused by insufficient nutrient and oxygen supplies resulting from damaged peripheral arteries. The lack of nutrients and oxygen causes severe tissue damage in the limb, thereby resulting in severe morbidities and mortality. The therapeutic effects of the conventional treatments are still not sufficient. Cell transplantations in small animal model (mice) are vital for deciphering the mechanisms of MSCs’ action in muscle regeneration. The stimulation of angiogenesis is a promising strategy for the treatment of ischemic limbs, restoring blood supply for the ischemic region. In the present study, we focus on the therapeutic properties of the human WJ-MSCs derived product, Cardio. We investigated the role of CardioCell in promoting angiogenesis and relieving hindlimb ischemia. Our results confirm the healing effect of CardioCell and strongly support the use of the WJ-MSCs in regenerative medicine.
The growing number of female reproductive system disorders creates a need for novel treatment methods. Tissue engineering brings hope for patients, which enables damaged tissue reconstruction. For this purpose, epithelial cells are cultured on three-dimensional scaffolds. One of the most promising materials is chitosan, which is known for its biocompatibility and biodegradability. The aim of the following study was to verify the potential of chitosan-based biomaterials for pelvic organ prolapse regeneration. The scaffolds were obtained under microwave-assisted conditions in crosslinking reactions, using dicarboxylic acids and aminoacid as crosslinkers, including l-glutamic acid, adipic acid, malonic acid, and levulinic acid. The products were characterized over their physicochemical and biological properties. FT–IR analysis confirmed formation of amide bonds. The scaffolds had a highly porous structure, which was confirmed by SEM analysis. Their porosity was above 90%. The biomaterials had excellent swelling abilities and very good antioxidant properties. The cytotoxicity study was performed on vaginal epithelial VK2/E6E7 and human colon cancer HCT116 cell lines. The results showed that after certain modifications, the proposed scaffolds could be used in pelvic organ prolapse (POP) treatment.