Multipotent Mesenchymal Stem Cells Research Articles

Enhanced osteogenic differentiation potential of Arnica montana and Bellis perennis in C3H10T1/2 multipotent mesenchymal stem cells.

Arnica montanaandBellis perennisare two medicinal plants that are thought to accelerate bone repair in homoeopathic literature. Mesenchymal stem cells (MSCs) are multipotent stem cells with the ability to differentiate and regenerate bone or osteogenesis.Hence, we aimed to determine the role ofArnica montanaandBellis perennison the osteogenic differentiation of the C3H10T1/2 stem cell line. The cell proliferation ofArnica montanaandBellis perenniswas evaluated by MTT assay. Osteogenic differentiation of C3H10T1/2 was induced by the addition of β-glycerophosphate, ascorbic acid and dexamethasone in the differentiation medium over 3 weeks. Cells were treated with Arnica montana andBellis perennis individually as well as in combination. The osteogenic differentiation potential ofArnica montana andBellis perennis to differentiate C3H10T1/2 into osteoblasts was measured by alkaline phosphatase activity, alizarin red staining and the expression of Osteocalcin using immunostaining and qRT-PCR. Arnica montana and Bellis perennis could enhance C3H10T1/2 cell proliferation at 1600µg. Further, the compound showed the ability to augment osteogenesis as confirmed by increased expression of alkaline phosphatase and enhanced calcium accumulation as seen by the Alizarin Red staining and quantification. Enhanced osteogenesis was further supported by the increased expression of osteocalcin in the treated cells with individual and combined doses of Arnica montana and Bellis perennis. Therefore, the findings provide additional support for the positive impact of Arnica montana and Bellis perennis on bone formation. Our findings suggest that homoeopathic compoundsArnica montanaandBellis perenniscan augment osteogenesis individually as well as in combination.

PRRX1 upregulates PD-L1 in human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in clinical applications for the amelioration of immune disorders, including graft-versus-host disease (GvHD) and Crohn's disease. The immunosuppressive role of Programmed death-ligand 1 (PD-L1) in MSCs is pivotal, yet the regulatory mechanisms governing its expression remain to be fully elucidated. In this study, we explored the influence of paired-related homeobox (PRRX1), a determinant of multipotency and self-renewal in MSCs, on the expression of various surface antigens, notably PD-L1. Multiple isoforms of PRRX1 were found to augment the mRNA levels of MSC markers, such as CD26 and CD317, with all isoforms elevating PD-L1 expression at both mRNA and protein levels. This study reveals that PRRX1 may act as a potential immunomodulatory factor in MSCs by regulating the PD-L1 pathway.

How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation.

Mesenchymal stem cells (MSCs) are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts, chondrocytes and adipocytes. The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes, in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes. Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis. However, the mechanism underlying the adipogenic differentiation of MSCs is not fully understood. Here, the current knowledge of adipogenic differentiation in MSCs is reviewed, focusing on signaling pathways, noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation. Finally, the relationship between maladipogenic differentiation and diseases is briefly discussed. We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Abstract 5614: Mechanical regulation of cisplatin-DNA adduct repair in mesenchymal stem cells

Abstract This study examined whether loss of mechanotransduction in pluripotent mesenchymal stem cells (MSCs) disrupted repair of bulky DNA adducts, such as those induced by ultraviolet light or cisplatin. MSCs are important for the maintenance and responsiveness of skeletal tissues to environmental mechanical challenges. Beyond regulating proliferative and differentiative capacity of MSCs, emerging evidence suggests that physical activity is associated with improved recovery from DNA damage caused by environmental genotoxic stressors associated with stress and aging. Highlighting the possible crosstalk between DNA repair and bone health, defects in nucleotide excision repair (NER), which removes bulky DNA adducts, are associated with myelosuppression and progeroid aging phenotypes that result in bone defects and lipidodystrophies in mice. Cancer, early aging syndromes, and certain musculoskeletal diseases are associated with disruption of the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that transduces environmental mechanical signals from the extracellular matrix into the nucleus of a cell. Loss of LINC complex elements is associated with breast cancer progression and poorer prognosis. We hypothesize that LINC-mediated mechanical stimulation into the nucleus is critical for repair of bulky DNA adducts. Our pilot project showed that mechanical stimulation applied in the form of low intensity vibration (LIV) improved NER of cisplatin-induced DNA adducts in cultured MSCs. Our findings show a 20% increase in repair of cisplatin-induced DNA adducts in LIV treated samples compared to non-vibrated samples at 24 hours (P<0.005). We also quantified the effect of LINC complex disruption on cisplatin-induced DNA damage removal. Intact MSCs showed significant adduct removal after 24 hours, while LINC disruption significantly reduced DNA repair (P<0.001). Furthermore, initial experiments suggest that LINC disrupted cells do not arrest at DNA repair checkpoints, therefore, loss of LINC complex may reduce entry into senescence increasing DNA mutagenesis. In conclusion, these findings suggest a novel interaction between mechanical stimulation, the DNA damage response, and LINC complex in DNA repair in multipotent mesenchymal stem cells. Furthermore, we suggest that LINC-mediated mechanical changes associated with LIV treatment may lead to novel therapeutic approaches to combat deleterious musculoskeletal conditions associated with anti-cancer treatments. Citation Format: Anamaria Gabriella Zavala, Nina Nikitina, Crystal Cantu, Dalia DeLaCruz, Gunes Uzer. Mechanical regulation of cisplatin-DNA adduct repair in mesenchymal stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5614.

Influence of Different Photobiomodulation Parameters on Multi-Potent Adipose Tissue Mesenchymal Cells In Vitro.

Objective: Investigating the effect of different parameters of photobiomodulation (PBM) with low-power laser on multi-potent mesenchymal stem cells (MSCs) derived from adipose tissue in terms of proliferation and cell death. Methods: MSCs were submitted to PBM applications with combinations of the following physical parameters: control group (no intervention), wavelengths of 660 and 830 nm; energy of 0.5, 2, and 4 J; and power of 40 and 100 mW. MSC analysis was performed using MetaXpress® software at 24, 48, and 72 h. Results: Irradiation promoted a significant increase in cell proliferation (p < 0.05), with 830 nm laser, 100 mW, with energy of 0.5, 2, and 4 J in relation to the control group at all times. PBM with 660 nm, power of 40 mW, and energy of 0.5, 2, and 4 J produced greater cell death at 24 h compared with the control group. At the time of 72 h, there was no significant difference concerning cell death. Conclusions: According to the results found, we can conclude that both wavelengths were effective; however, the 830 nm laser was more effective in terms of cell proliferation compared with the 660 nm laser. The 660 nm wavelength showed a significant increase in cell death when compared with the 830 nm laser.

Potential Effect of Bovine Colostrum on Mesenchymal Stem Cells for Regenerative Therapy

Bovine colostrum is the first mammary secretion after parturition; it is rich in Igs and bioactive compounds and could play a role in the development of naturally based products with positive effects on human health. In this discussion, we critically examine the effect of bovine colostrum on the properties of mesenchymal stem cells. Multipotent mesenchymal stem cells (MSCs) are a heterogeneous subset of fibroblast-like cells that can be isolated from various biological tissues, such as bone marrow, umbilical cord, and adipose tissues. They are characterized by their ability to self-renew and differentiate into cells of the mesodermal lineage, including adipocytes, osteocytes, and chondrocytes. Additionally, MSCs display an immunomodulatory capacity due to their ability to interact with effector cells typical of both innate and adaptive immune responses. Considering these important properties, MSCs have gained increasing attention in the field of regenerative medicine in recent decades. To date, most experimental protocols are based on cell culture media supplemented with fetal bovine serum (FBS) to promote the ex vivo expansion of MSCs while preserving their differentiative and immunomodulatory capacities. Future trends could involve the application of bovine colostrum in regenerative medicine.

The exo-microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs).

A major factor in long-term impairment is stroke. Patients with persistent stroke and severe functional disabilities have few therapy choices. Longnoncoding RNAs (lncRNAs) may contribute to the regulation of the pathophysiologic processes of ischemic stroke as shown by altered expression of lncRNAsand microRNA (miRNAs) in blood samples of acute ischemic stroke patients. On the other hand, multipotent mesenchymal stem cells (MSCs) increase neurogenesis, and angiogenesis, dampen neuroinflammation, and boost brain plasticity to improve functional recovery in experimental stroke models. MSCs can be procured from various sources such as the bone marrow, adipose tissue, and peripheral blood. Under the proper circumstances, MSCs can differentiate into a variety of mature cells, including neurons, astrocytes, and oligodendrocytes. Accordingly, the capability of MSCs to exert neuroprotection and also neurogenesis has recently attracted more attention. Nowadays, lncRNAs and miRNAs derived from MSCs have opened new avenues to alleviate stroke symptoms. Accordingly, in this review article, we examined various studies concerning the lncRNAs and miRNAs'role in stroke pathogenesis and delivered an overview of the therapeutic role of MSC-derived miRNAs and lncRNAs in stroke conditions.

Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions of mast cells and T cells

Contact urticaria (CU) is an inflammatory skin disorder triggered by specific substances upon skin contact, leading to immediate acute or chronic manifestations characterized by swelling and redness. While mesenchymal stem cells (MSCs) are increasingly recognized for their therapeutic potential in immune diseases, research on the efficacy and mechanisms of stem cell therapy for urticaria remains scarce. This study investigates the regulatory role of embryonic-stem-cell-derived multipotent MSCs (M-MSCs) administered in a CU mouse model. Therapeutic effects of M-MSC administration were assessed in a Trimellitic anhydride-induced contact urticaria model, revealing significant inhibition of urticarial reactions, including ear swelling, itchiness, and skin lesion. Moreover, M-MSC administration exerted control over effector T cell activities in major lymphoid and peripheral tissues, while also suppressing mast cell degranulation in peripheral tissues. Notably, the inhibitory effects mediated by M-MSCs were found to be TGF-β-dependent. Our study demonstrates the capacity of M-MSCs to regulate contact urticaria in a murine model, harmonizing the activation of inflammatory T cells and mast cells. Additionally, we suggest that TGF-β derived from M-MSCs could play a pivotal role as an inhibitory mechanism in contact urticaria.

Comparison of the therapeutic effect of native and preconditioned human umbilical cord-derived multipotent mesenchymal stromal cells on a rat model of acute pancreatitis

Pancreatitis is a disease characterized by an acute or chronic inflammatory process of the pancreas, induced by the activation of trypsin inside acinocytes. These processes result in necrosis of the organ's parenchyma, abscess formation, and systemic complications, contributing to patient mortality rates ranging from 30-47%. As of now, there is no globally recognized effective treatment for acute pancreatitis. Multipotent mesenchymal stem cells (MMSCs) are potential candidates for treating this disease due to their immunomodulatory properties. The aim of this study was to compare the therapeutic effects of transplanting native human umbilical cord-derived MMSCs (hUC-MMSCs) with hUC-MMSCs preconditioned with H2O2 in a rat model of acute pancreatitis. Materials and methods. Acute pancreatitis in rats was induced by intraperitoneal injection of L-arginine at a dose of 3.5 g/kg body weight at an interval of 1 hour. The rats were then categorized into four groups. Group 1 – negative control, where animals received a physiological solution; group 2 – positive control (pancreatitis). Three days after the onset of signs of developed acute pancreatitis, group 3 rats were intraperitoneally transplanted with native hUC-MMSCs, meeting the minimum criteria of the International Society for Cell and Gene Therapy, at a dose of 1.5×106 cells/kg. Group 4 received the same dose of hUC-MMSCs, but these cells were preconditioned with H2O2 at a concentration of 30 µM for 18 hours. The effects of both native and preconditioned hUC-MMSCs were evaluated at 3, 7, and 14 days after their introduction. Assessment criteria included the α-amylase index, identification of insulin in the islets of Langerhans, and histological analysis. Results. It was demonstrated that, three days post L-arginine administration, the α-amylase level surged by five times compared to the negative control, and blood glucose levels increased by 2.5 times, indicating damage to both the exocrine and endocrine parts of the pancreas. Microscopic examination revealed a 3.5-fold increase in fibrosis of the pancreatic parenchyma compared to the negative control. Three days after the transplantation of native hUC-MMSCs, the α-amylase level in the blood decreased by 1.7 times, and in the variant with preconditioned hUC-MMSCs, it decreased by 2 times compared to Group 2. By day 7, the α-amylase index in the native hUC-MMSCs group decreased by 2.4 times compared to the positive control, and in the preconditioned hUC-MMSCs group, it approached normal levels. A gradual recovery of the pancreatic architecture was observed by day 7, with a faster recovery in the preconditioned MMSCs group. Histological sections revealed a replacement of nuclei-free areas with acinocytes, indicated by a 3-fold decrease in the number of nuclei-free cells in the native hUC-MMSCs transplantation, and almost normal levels in the preconditioned hUC-MMSCs group. Both variants exhibited a positive histochemical PAS-reaction for the identification of insulin in the islets of Langerhans, and blood glucose levels corresponded to the norm. After 14 days, complete recovery of the pancreas was observed in both variants. Conclusion. The study results indicate that hUC-MMSCs transplantation in rats with acute pancreatitis contributes to the restoration of pancreatic parenchyma architecture and function. Moreover, the administration of MMSCs preconditioned with H2O2 significantly enhances the therapeutic effect, expediting the recovery process of the pancreas in animals.

The Optimal Cryo Revival Period of Cryopreserved Wharton's Jelly Derived- Mesenchymal Stem Cells

The workflow of cryopreservation is a challenging step in the standardised preparation of cell therapy products in terms of methods used (i.e., adapted controls of the work environment, quality control, reagents, and equipment). This study aimed to determine the effect of cryopreservation on the stability of mesenchymal stem cell (MSC) characteristics by comparing fresh cells with those that underwent different post-thaw cell recovery periods. The MSCs were derived from human Wharton’s jelly umbilical cord (n = 4). The cells that were cryopreserved for 7 days were revived at 0 h (CRC-0h), 24 h (CRC-24h) and 7 days (CRC-7d) and then evaluated on the basis of cell viability, doubling time, morphology, trilineage differentiation potential, growth kinetics, and MSC surface marker expression. The cell viability of the CRC-0h group was 90%, whereas that of the CRC-24h group was 80%-85%. Cell attachment results showed that CRC-24h had a notably higher attachment rate than the other two groups. The CRC groups showed CD90, CD73 or CD44 expression, which meets the minimum criteria for defining multipotent MSCs. By contrast, CD105 expression was significantly reduced in the CRC groups and was lower than the minimum requirement based on the standards of the International Society for Cellular Therapy. Results suggest that at least 24 h is necessary to improve the quality of MSCs for it to be adequate for cell therapy use.

LINC01638 sustains human mesenchymal stem cell self-renewal and competency for osteogenic cell fate

The skeleton forms from multipotent human mesenchymal stem cells (hMSCs) competent to commit to specific lineages. Long noncoding RNAs (lncRNAs) have been identified as key epigenetic regulators of tissue development. However, regulation of osteogenesis by lncRNAs as mediators of commitment to the bone phenotype is largely unexplored. We focused on LINC01638, which is highly expressed in hMSCs and has been studied in cancers, but not in regulating osteogenesis. We demonstrated that LINC01638 promotes initiation of the osteoblast phenotype. Our findings reveal that LINC01638 is present at low levels during the induction of osteoblast differentiation. CRISPRi knockdown of LINC01638 in MSCs prevents osteogenesis and alkaline phosphatase expression, inhibiting osteoblast differentiation. This resulted in decreased MSC growth rate, accompanied by double-strand breaks, DNA damage, and cell senescence. Transcriptome profiling of control and LINC01638-depleted hMSCs identified > 2000 differentially expressed mRNAs related to cell cycle, cell division, spindle formation, DNA repair, and osteogenesis. Using ChIRP-qPCR, molecular mechanisms of chromatin interactions revealed the LINC01638 locus (Chr 22) includes many lncRNAs and bone-related genes. These novel findings identify the obligatory role for LINC01638 to sustain MSC pluripotency regulating osteoblast commitment and growth, as well as for physiological remodeling of bone tissue.

Safety assessment of the femtosecond laser in corneal limbal graft excision

Objective: to study in vitro survival and preservation of the proliferative activity of limbal stem cells (LSCs) in femtosecond laser-cut limbal tissue fragments. Materials and methods. Limbal fragments were formed from donor cadaver eyes (n = 8) in the upper and lower limbus containing the highest number of limbal stem cells, using a Z8 femtosecond laser (FSL) (Ziemer, Switzerland). The limbal fragments were fragmented into 4 mini-grafts using different energy levels (100, 110, 120%). Mini-grafts from symmetrical sections of the cadaver eyes, which were manually isolated using a microsurgical blade, served as controls. The mini-grafts were cultured for two weeks in culture media intended for limbal epithelial stem cells (LESCs) (Epilife (0.06 mM Ca++) and for multipotent mesenchymal stem cells (MMSCs) (DMEM/F12), with the addition of specific growth factors to selectively stimulate LESCs or MMSCs, respectively. The phenotype of the obtained cultured cells in the «laser» and «knife» groups was determined by flow cytometry using a set of markers (CD166, CD105, CD90, CD29, CD34) for the membrane proteins of LESCs and MMSCs. The ability of cultured cells to adhesion and proliferation in the «laser» and «knife» groups was determined by seeding the third passage of the resulting cultures on Bowman’s membrane of acellular corneas.Results. Primary cell culture was obtained from mini-grafts of all donors in both groups. Cell morphology was consistent with the phenotype of corneal epithelial cells (cobblestone pattern). When cultured in the EpiLife medium (0.06 mM Ca++), we determined the presence of LSCs proliferation from 38.6% of minigrafts; in the DMEM/F12 medium (1 : 1) the presence was determined from 31.8%. Two weeks later, cell yield from mini-grafts in the «laser» and «knife» groups was 77.2% and 63.6%, respectively. Cell growth by the end of week 2 of culturing of mini-grafts obtained by FSL at 120, 110 and 100% energies was 87.5, 71.4 and 71.4%, respectively. It was found that the resulting cell cultures in the «laser» and «knife» groups and in the «120%», «110%» and «100%» subgroups were not different phenotypically. Cytofluorimetric analysis showed that cell cultures in the groups had a mixed pattern of marker expression of both LESCs (CD29+) and MMSCs (CD90+, CD105+). Seeding of the third passage of cell culture in the test groups in all cases demonstrated adhesion and formation of a cell monolayer on the Bowman’s membrane of model corneas.Conclusion. The use of FSL for cutting out limbal grafts seems to be effective and safe in comparison with the traditional mechanical (knife) technique. Cell cultures obtained from FSL-cut mini-grafts were able to grow and migrate for at least 21 days.

Regulation of self-renewal and senescence in primitive mesenchymal stem cells by Wnt and TGFβ signaling

BackgroundThe therapeutic application of multipotent mesenchymal stem cells (MSCs) encounters significant challenges, primarily stemming from their inadequate growth and limited self-renewal capabilities. Additionally, as MSCs are propagated, their ability to self-renew declines, and the exact cellular and molecular changes responsible for this are poorly understood. This study aims to uncover the complex molecular mechanisms that govern the self-renewal of primitive (p) MSCs.MethodsWe grew pMSCs using two types of medium, fetal bovine serum (FM) and xeno-free (XM), at both low passage (LP, P3) and high passage (HP, P20). To evaluate LP and HP pMSCs, we examined their physical characteristics, cell surface markers, growth rate, colony-forming ability, BrdU assays for proliferation, telomerase activity, and potential to differentiate into three lineages. Moreover, we conducted RNA-seq to analyze their transcriptome and MNase-seq analysis to investigate nucleosome occupancies.ResultsWhen grown in FM, pMSCs underwent changes in their cellular morphology, becoming larger and elongated. This was accompanied by a decrease in the expression of CD90 and CD49f, as well as a reduction in CFE, proliferation rate, and telomerase activity. In addition, these cells showed an increased tendency to differentiate into the adipogenic lineage. However, when grown in XM, pMSCs maintained their self-renewal capacity and ability to differentiate into multiple lineages while preserving their fibroblastoid morphology. Transcriptomic analysis showed an upregulation of genes associated with self-renewal, cell cycle regulation, and DNA replication in XM-cultured pMSCs, while senescence-related genes were upregulated in FM-cultured cells. Further analysis demonstrated differential nucleosomal occupancies in self-renewal and senescence-related genes for pMSCs grown in XM and FM, respectively. These findings were confirmed by qRT-PCR analysis, which revealed alterations in the expression of genes related to self-renewal, cell cycle regulation, DNA replication, differentiation, and senescence. To understand the underlying mechanisms, we investigated the involvement of Wnt and TGFβ signaling pathways by modulating them with agonists and antagonists. This experimental manipulation led to the upregulation and downregulation of self-renewal genes in pMSCs, providing further insights into the signaling pathways governing the self-renewal and senescence of pMSCs.ConclusionOur study shows that the self-renewal potential of pMSCs is associated with the Wnt pathway, while senescence is linked to TGFβ.

Apoptotic effects of mesenchymal stem cells’ conditioned medium on colorectal cancer cell lines

Multipotent Mesenchymal stem cells (MSCs) have vigorous immunomodulatory activity, apoptotic effects, and the capacity to migrate to inflammatory and tumor sites. This study focuses on the apoptotic effects of MSCs conditioned medium (CM) on colorectal cancer cell lines. MSCs were preconditioned with lipopolysaccharide (LPS) to induce apoptosis in colorectal cancer cells. The conditioned medium (LPS-CM) from the preconditioned cells was isolated and used to treat colorectal cancer cells (HT29 and SW48). The survival and proliferation of cancer cells were assessed using Trypan blue staining and MTT assay. The apoptosis rate was evaluated through flow cytometry analysis and caspase-3 activity. Additionally, Real-Time PCR was used to measure the mRNA level of apoptotic and anti-apoptotic factors, including bcl2, bax, and p53 genes. The results showed that LPS-CM significantly increased (p < 0.001) the percentage of apoptosis in the SW48 and HT29 cell lines. Caspase-3 activity significantly increased (p < 0.001) in these cell lines after treatment with LPS-CM. The mRNA level of bcl2 was significantly decreased (p < 0.001), while bax and p53 genes were significantly overexpressed (p < 0.001) in the LPS-CM treated cell lines. Notably, the mRNA level of bcl2 and bax genes was significantly altered at a higher concentration of LPS-CM. In conclusion, the conditioned medium from LPS-preconditioned MSCs can effectively induce apoptosis in colorectal cancer cells. This finding suggests that LPS-CM could be a potential strategy for inhibiting the proliferation and progression of colorectal cancer cells.

NexGen regen? Challenges and opportunities for growth factors and signaling agents in periodontal regeneration at intrabony defects

Regeneration of periodontal tissues that have been destroyed by inflammatory periodontitis involves the initiation of tissue engineering and wound healing of multiple tissues involved in the function of the teeth, including the periodontal ligament, cementum, and alveolar bone. Such regeneration is termed guided tissue regeneration and the unique challenges to reconstruct these tissues involves a complex interplay of cells, signaling molecules, and scaffolds. While traditional guided tissue regeneration treatments have involved cell occlusive membranes, bone replacement graft scaffolds, and endogenous multipotent mesenchymal stem cells, the use of adjunctive materials to enhance healing outcomes has been studied and many such adjunctive factors are in common current clinical use. This report will focus on the current and emerging adjunctive growth factors and signaling molecules that can be used to optimize periodontal regeneration in periodontal intrabony defects, their mechanisms of action, the challenges associated with periodontal regeneration, and future avenues for research.

New insights in application of mesenchymal stem cells therapy in tumor microenvironment: pros and cons.

Multipotent mesenchymal stem cells (MSCs) are widely accepted as a useful tool for cell-based therapy of various diseases including malignancies. The therapeutic effects of MSCs are mainly attributed to their immunomodulatory and immunosuppressive properties. Despite the promising outcomes of MSCs in cancer therapy, a growing body of evidence implies that MSCs also show tumorigenic properties in the tumor microenvironment (TME), which might lead to tumor induction and progression. Owing to the broad-spectrum applications of MSCs, this challenge needs to be tackled so that they can be safely utilized in clinical practice. Herein, we review the diverse activities of MSCs in TME and highlight the potential methods to convert their protumorigenic characteristics into onco-suppressive effects.

Immunomodulatory effects of mesenchymal stem cells on B and T cells

Mesenchymal stem cells (MSCs) or adult multipotent progenitor cells with the ability to self-renew and differentiate, are extracted from a variety of tissues, including bone marrow, adipose tissue, umbilical cord blood, Wharton’s jelly, tooth pulp, menstrual blood, and others. Since they are multipotent, cultured MSCs can differentiate into the adipogenic, chondrogenic, and osteogenic lineages after being isolated. Due to their immunomodulatory, immunosuppressive, and regenerative potentials, multipotent mesenchymal stem cells (MSCs) have received extensive scrutiny as an efficient tool for cell-based therapy of inflammatory, immune-mediated, and degenerative illnesses. Mesenchymal stem cells (MSCs) have been the subject of numerous preclinical and clinical research that looked into their therapeutic potential. This potential is primarily supported by MSCs' immunosuppressive characteristics. Even while there is still much to learn about the therapeutic characteristics of MSC transplantation, mounting evidence suggests that T and B cells undergo changes after MSC infusion, most notably the induction of regulatory T (Tregs) and B (Bregs) cells. Tregs and Bregs have been shown to exhibit immunosuppressive properties, and these cells are being considered as potential novel targets for the therapy of inflammatory disorders.

A review on mesenchymal stem cell-based therapies for autoimmune disorders

Mesenchymal stem cells (MSCs) or adult multipotent progenitor cells with the ability to self- renew and differentiate, are extracted from a variety of tissues, including bone marrow, adipose tissue, umbilical cord blood, Wharton’s jelly, tooth pulp, menstrual blood, and others. Since they are multipotent, cultured MSCs can differentiate into the adipogenic, chondrogenic, and osteogenic lineages after being isolated. Due to their immunomodulatory, immunosuppressive, and regenerative potentials, multipotent mesenchymal stem cells (MSCs) have received extensive scrutiny as an efficient tool for cell-based therapy of inflammatory, immune- mediated, and degenerative illnesses. The clinical applications and therapeutic potential of this cell type, the therapeutic mechanisms of MSCs, techniques to increase their therapeutic potentials, such as manipulation and preconditioning, and potential/unexpected risks that should be taken into account as a preliminary step before they are put to clinical use. In large part, due to their distinct immunomodulatory capabilities, MSCs have been touted as an ideal choice for the treatment of immune-related illnesses throughout the past few decades. In this review study we are mainly focusing on the MSC based treatments currently being developed for autoimmune diseases, type 1 diabetes and rheumatoid arthritis.

Histomorphological examination of the alveolar bone in periodontitis in an experiment

RELEVANCE: The article presents the results of an experimental study conducted on Wistar rats. The creation of artificial periodontitis was carried out. The developed method of treatment using multipotent stem cells and an osteogenesis stimulator was applied.&#x0D; AIM: Improvement of methods of treatment of chronic periodontitis by enhancing bone regeneration. To study the histomorphological picture and the nature of clinical changes in the tissues of a pathologically altered periodontal in an experiment.&#x0D; MATERIAL AND METHODS: Experimental studies were conducted at the Department of Therapeutic Dentistry with a course of IDPO, in the central research laboratory, the laboratory of cell cultures, the immuno-histochemical laboratory of the BSMU of the Ministry of Health of Russia. Observation period: 2020-2022 Prior to the experimental studies, multipotent mesenchymal stem cells were isolated from the pulp of a removed retinated human tooth. For the experiment, sexually mature Wistar rats in the amount of 50 individuals were used as a model. Experimental modeling of bone tissue destruction in periodontal was performed on the upper jaw in the area of the second molar and on the incisors of the lower jaw of rats. The obtained MMSCs were mixed with a drug stimulator of osteogenesis. The resulting mixture was introduced into the bone (periodontal) pockets of rats. A Septopak protective bandage was applied to fix the mass. The course of treatment is 3 procedures with an interval of 5 days. Observation of rats after the course of treatment was carried out in terms from 1 to 12 months.&#x0D; RESULTS: Experimental studies have shown a pronounced therapeutic effectiveness of using the method for the treatment of destructive changes in the alveolar bone in periodontitis, the possibility of complete restoration of the dentoalveolar papillae, as well as regeneration of periodontal tissues in the area of experimental destruction of bone tissue in periodontitis during the first 35 days. At the same time, there was a complete absence of signs of inflammation in the main group (bleeding, pathological mobility of teeth and gum discharge during palpation), which confirms the pronounced therapeutic effect of mesenchymal stem cells and an osteogenesis stimulator.