Potential use of human periapical cyst-mesenchymal stem cells (hPCy-MSCs) as a novel stem cell source for regenerative medicine applications

Mesenchymal stem cells (MSCs) are attracting growing interest by the scientific community due to their huge regenerative potential. Thus, the plasticity of MSCs strongly suggests the utilization of these cells for regenerative medicine applications. The main issue about the clinical use of MSCs is related to the complex way to obtain them from healthy tissues; this topic has encouraged scientists to search for novel and more advantageous sources of these cells in easily accessible tissues. The oral cavity hosts several cell populations expressing mesenchymal stem cell like-features, furthermore, the access to oral and dental tissues is simple and isolation of cells is very efficient. Thus, oral-derived stem cells are highly attractive for clinical purposes. In this context, human periapical cyst mesenchymal stem cells (hPCy-MSCs) exhibit characteristics similar to other dental-derived MSCs, including their extensive proliferative potential, cell surface marker profile and the ability to differentiate into various cell types such as osteoblasts, adipocytes and neurons. Importantly, hPCy-MSCs are easily collected from the surgically removed periapical cysts; this reusing of biological waste guarantees a smart source of stem cells without any impact on the surrounding healthy tissues. In this review, we report the most interesting research topics related to hPCy-MSCs with a newsworthy discussion about the future insights. This newly discovered cell population exhibits interesting and valuable potentialities that could be of high impact in the future regenerative medicine applications

Generation of Human Epidermis-Derived Mesenchymal Stem Cell-like Pluripotent Cells and their reprogramming in mouse chimeras

Stem cells can be derived from the embryo (embryonic stem cells, ESCs), from adult tissues (adult stem cells, ASCs), and by induction of fibroblasts (induced pluripotent stem cells, iPSs). Ethical problems, immunological rejection, and difficulties in obtaining human tissues limit the use of ESCs in clinical medicine. Induced pluripotent stem cells are difficult to maintain in vitro and carry a greater risk of tumor formation. Furthermore, the complexity of maintenance and propagation is especially difficult in the clinic. Adult stem cells can be isolated from several adult tissues and present the possibility of self-transplantation for the clinical treatment of a variety of human diseases. Recently, several ASCs have been successfully isolated and cultured in vitro, including hematopoietic stem cells (HSCs) , mesenchymal stem cells (MSCs), epidermis stem cells, neural stem cells (NSCs), adipose-derived stem cells (ADSCs), islet stem cells, and germ line stem cells. Human mesenchymal stem cells originate mainly from bone marrow, cord blood, and placenta, but epidermis-derived MSCs have not yet been isolated. We isolated small spindle-shaped cells with strong proliferative potential during the culture of human epidermis cells and designed a medium to isolate and propagate these cells. They resembled MSCs morphologically and demonstrated pluripotency in vivo; thus, we defined these cells as human epidermis-derived mesenchymal stem cell-like pluripotent cells (hEMSCPCs). These hEMSCPCs present a possible new cell resource for tissue engineering and regenerative medicine

Immunomodulatory effects of human umbilical cord wharton's Jelly-Derived mesenchymal stem cells on differentiation, maturation and endocytosis of monocyte-derived dendritic cells

The Wharton's jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases. In this study, we investigated the immunomodulatory effect of umbilical cord derivedmesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately cocultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cellcell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naive T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses. Copyright © Spring 2013, Iran J Allergy Asthma Immunol. All rights reserved

Regional Variations In The Immunohistochemical Expression Of P75 NGF Receptors Between Term And Post-Term Human Placenta

Background: The placenta has lately attracted increased attention due to its potential as a significant source of many types of stem cells, such as trophoblastic, hematopoietic, epithelial, and mesenchymal stem cells (MSCs). Placental cells are readily and ethically obtainable. In addition, the human placenta has the potential to provide a significant quantity of stem cells that can be readily isolated, expanded, and differentiated into several kinds of cells. Both the maternal and the fetal components of MSCs are present in the human placenta. Previous investigations have found that the origin of mesenchymal stem cells has a significant impact on their capacity to treat diseases. As a result, placental MSCs have a lot of potential for therapeutic use. Compared to the immunomodulatory activity of MSCs derived from mothers, fetal MSCs have a higher capacity to promote immunological health. The p75 protein has been demonstrated to be the most effective marker for the isolation and identification of human bone marrow-derived mesenchymal stem cells. CD271 was considered a versatile marker that would allow the isolation and culture of multipotent stem cells derived from mesenchymal tissue. No prior work reported P75 NGFR utilized in placental tissues as a marker for mesenchymal stem cells in connection to various gestational ages (term, and post-term) and diverse placental locations including (chorionic plate and placental villi sides)

Effect of secretory factors from mesenchymal stem cell pulsed with nicotine on the neutrophils functions

Background and aims: The effects of the mesenchymal stem cells (MSCs) on the neutrophil functions has been revealed in recent documents. Moreover, it has been showed that mesenchymal stem cells (MSCs) express some of the nicotinic receptor subunits. The aim of the present study was to determine the effects of the secretory factors from mesenchymal stem cell pulsed with nicotine on the neutrophil functions. Methods: After isolation of mesenchymal stem cells from bone marrow of rats, these cells pulsed with different concentration of nicotine (0, 0.1, 0.5 and 1 µM) for 48h. Then, neutrophils were co-cultured with MSCs supernatants for 4 h and the functions of neutrophils were evaluated. Results: The results showed that MSCs supernatants pulsed with nicotine could significantly enhance the viability and phagocytic activity of neutrophils more profound that MSCs supernatants without treatment. Furthermore, supernatants of MSCs treated with nicotine significantly reduced the respiratory burst and nitric oxide production of neutrophils more prominent than and /or supernatants of the MSCs without treatment. Conclusion: Collectively, these findings may offer new insight into the potential mechanisms underlying the immunomodulatory and anti-inflammatory effects of nicotine

Comparison of the Modulated Effects of Tretinoin and Calcitriol Treated Mesenchymal Stem Cell Supernatant on Macrophage Functions

Background: According to a number of studies, calcitriol and tretinoin are able to regulate differentiation as well as the growth and of mesenchymal stem cells (MSCs). Nevertheless, the relationship between the supernatant of macrophage and mesenchymal stem cells is still under investigation. In the present work, a comparison is made between the modulated impacts of calcitriol and tretinoin treated mesenchymal stem cell supernatant on macrophage functions. Materials and Methods: The isolation of mesenchymal stem cells was done using mouse bone marrow and the various concentrations of calcitriol (200 and 400 nM) and tretinoin (25, 50, and 100 nM) were used to pulse MSCs for 48 h. Macrophages were then applied to co-culture the supernatant of MSCs for 4 hr. Consequently, macrophages were assessed for respiratory burst. Results:  Based on the obtained results, supernatant of bone marrow‐derived MSCs pulsed with calcitriol and tretinoin can have the potential for decreasing the respiratory burst of macrophages considerably in comparison with the control group.  Conclusion: The anti‐inflammatory M2 macrophage polarization can be accelerated using calcitriol and tretinoin by mesenchymal stem cells

Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications

The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search enginesWeb of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.Junta de Andalucia"5 per mille" research grant 73042

Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas

Muscle-Bound Primordial Stem Cells Give Rise to Myofiber-Associated Myogenic and Non-Myogenic Progenitors

Myofiber cultures give rise to myogenic as well as to non-myogenic cells. Whether these myofiber-associated non-myogenic cells develop from resident stem cells that possess mesenchymal plasticity or from other stem cells such as mesenchymal stem cells (MSCs) remain unsolved. To address this question, we applied a method for reconstructing cell lineage trees from somatic mutations to MSCs and myogenic and non-myogenic cells from individual myofibers that were cultured at clonal density

Mesenchymal stem cells for management of rheumatoid arthritis : immune modulation, repair or both?

The authors are grateful for support to their research from Arthritis Research UK (grants 19271, 19429, 19667, 20050, 20775) and the Medical Research Council (grant no. MR/L020211/1)Peer reviewedPostprin