Toward the latest advancements in cardiac regeneration using induced pluripotent stem cells (iPSCs) technology: approaches and challenges.

A novel approach to treating heart failures was developed with the introduction of iPSC technology. Knowledge in regenerative medicine, developmental biology, and the identification of illnesses at the cellular level has exploded since the discovery of iPSCs. One of the most frequent causes of mortality associated with cardiovascular disease is the loss of cardiomyocytes (CMs), followed by heart failure. A possible treatment for heart failure involves restoring cardiac function and replacing damaged tissue with healthy, regenerated CMs. Significant strides in stem cell biology during the last ten years have transformed the in vitro study of human illness and enhanced our knowledge of the molecular pathways underlying human disease, regenerative medicine, and drug development. We seek to examine iPSC advancements in disease modeling, drug discovery, iPSC-Based cell treatments, and purification methods in this article.

Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy.

Cell therapy has emerged as one of the most promising approaches to treating disease in recent decades. The application of stem cells in anti-tumor therapy is determined by their varying capacity for proliferation, migration, and differentiation. These capacities are derived from different sources. The use of stem cell carriers in cancer treatment is justified by the following three reasons: (I) shield therapeutic agents from swift biological deterioration; (II) reduce systemic side effects; and (III) increase local therapeutic levels since stem cells have an innate ability to target tumors. The quantity of stem cells confined to the tumor microenvironment determines this system's anti-tumor activity. Nevertheless, there are limitations to the use of different types of stem cells. When immune cells are used in cell therapy, it may lead to cytokine storms and improper reactions to self-antigens. Furthermore, the use of stem cells may result in cancer. Additionally, after an intravenous injection, cells could not migrate to the injury location. Exosomes derived from different cells were thus proposed as possible therapeutic options. Exosomes are becoming more and more well-liked because of their small size, biocompatibility, and simplicity in storage and separation. A number of investigations have shown that adding various medications and microRNAs to exosomes may enhance their therapeutic effectiveness. Thus, it is essential to evaluate studies looking into the therapeutic effectiveness of encapsulated exosomes. In this review, we looked at studies on encapsulated exosomes' use in regenerative medicine and the treatment of cancer. The results imply that the therapeutic potential increases when encapsulated exosomes are used rather than intact exosomes. Therefore, in order to optimize the effectiveness of the treatment, it is advised to implement this technique in accordance with the kind of therapy.

Cytokines secreted from bone marrow-derived mesenchymal stem cells promote apoptosis of CD34+ leukemic stem cells as anti-cancer therapy.

Objective: The effect of mesenchymal stem cells (MSCs) on the immortal characteristics of malignant cells, particularly hematologic cancer cells, remains a topic of debate, with the underlying mechanisms still requiring further elucidation. We explored the in vitro effect of the bone marrow-derived MSCs (BM-MSCs) on CD34+ leukemic stem cells (LSCs) enriched from the KG1-a cell line by assessing apoptosis, measuring cytokine levels, and examining TERT protein expression. Additionally, the potential signaling pathways implicated in this process, such as P53, PTEN, NF-κB, ERK1/2, Raf-1, and H-RAS, were also investigated. Methods: CD34+ LSCs were enriched from the KG1-a cell line with the magnetic activated cell sorting (MACS) method. Two cell populations (BM-MSCs and CD34+ LSCs) were co-cultured on trans well plates for seven days. Next, CD34+ LSCs were collected and subjected to Annexin V/PI assay, cytokine measurement, and western blotting. Results: BM-MSCs caused a significant increase in early and late apoptosis in the CD34+LSCs. The significant presence of interleukin (IL)-2 and IL-4 was evident in the co-cultured media. In addition, BM-MSCs significantly increased the protein expression of P53, PTEN, NF-κB, and significantly decreased p-ERK1/2, Raf-1, H-RAS, and TERT. Conclusion: The mentioned effects of IL-2 and IL-4 cytokines released from BM-MSCs on CD34+ LSCs as therapeutic agents were applied by the components of P53, PTEN, NF-κB, p-ERK1/2, Raf-1, and H-RAS signaling pathways.

Stem cells-derived exosomes as cardiac regenerative agents.

Heart failure is a root cause of morbidity and mortality worldwide. Due to the limited regenerative capacity of the heart following myocardial injury, stem cell-based therapies have been considered a hopeful approach for improving cardiac regeneration. In recent years, different kinds of cell products have been investigated regarding their potential to treat patients with heart failure. Despite special attention to cell therapy and its products, therapeutic efficacy has been disappointing, and clinical application is not affordable. In the past few years, a subset of small extracellular vehicles (EVs), commonly known as "exosomes," was reported to grant regenerative and cardioprotective signals at a value similar to their donor cells. The conceptual advantage is that they may be ideally used without evoking a relevant recipient immune response or other adverse effects associated with viable cells. The evidence related to their beneficial effects in animal models of heart failure is rapidly growing. However, there is remarkable heterogeneity regarding source cells, isolation process, effective dosage, and delivery mode. This brief review will focus on the latest research and debates on regenerative potential and cardiac repair of exosomes from different sources, such as cardiac/non-cardiac stem, somatic cells, and progenitor cells. Overall, the current state of research on exosomes as an experimental therapy for heart diseases will be discussed.

L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression.

BACKGROUND: Stem cell-based therapy has emerged as an attractive approach for regenerative medicine. Poor survival and maintenance of the cells used in regenerative medicine are considered as serious barriers to enhance the efficacy of the cell therapy. Using some antioxidants has been reported to prevent the aging of stem cells, and finding effective factors to reduce the senescence of these cells has impressive potential in cell therapy. The PI3K pathway adversely regulates the transcription factors known as FOXO, which are thought to have an inhibitory influence on cell proliferation. By downregulating FOXO and other targets, PI3K signaling controls the growth of cells. For this reason, the aim of the present study is to investigate the effect of L-carnitine (LC) as antioxidant on the cell proliferation and the protein expression of PI3K and FOXO. METHODS: For understanding the in vitro effect of LC on the PI3K and FOXO-1 expression of C-kit+ hematopoietic progenitor cells, the bone marrow mononuclear cells were isolated, and C-kit+ cells was enriched by the magnetic-activated cell sorting (MACS). Next, the identification of enriched C-kit+ cells were done by flowcytometry and immunocytochemistry. Then, C-kit+ cells were treated with 0.2 mM LC, the cells were collected at the end of the treatment period (48 h), and the proteins were extracted. In the following, the protein expression of PI3K and FOXO-1 was measured by western blotting. In addition, flowcytometry was done to assess the Ki-67 expression as a key marker for cell proliferation investigation. RESULTS: 0.2 mM LC cause to significantly decrease in the protein expression of PI3K and FOXO-1 (*P<0.05 and **P<0.01, respectively). Also, the expression of Ki-67 was significantly increased in the presence of 0.2 mM LC (***P<0.001). CONCLUSION: Briefly, LC can be considered an effective factor in increasing the proliferation of C-kit+ cells via some signaling pathways.

The role of the hematopoietic stem/progenitor cells-derived extracellular vesicles in hematopoiesis.

Hematopoietic stem cells (HSCs) are tightly regulated by specific microenvironments called niches to produce an appropriate number of mature blood cell types. Self-renewal and differentiation are two hallmarks of hematopoietic stem and progenitor cells, and their balance is critical for proper functioning of blood and immune cells throughout life. In addition to cell-intrinsic regulation, extrinsic cues within the bone marrow niche and systemic factors also affect the fate of HSCs. Despite this, many paracrine and endocrine factors that influence the function of hematopoietic cells remain unknown. In hematological malignancies, malignant cells remodel their niche into a permissive environment to enhance the survival of leukemic cells. These events are accompanied by loss of normal hematopoiesis. It is well known that extracellular vehicles (EVs) mediate intracellular interactions under physiological and pathological conditions. In other words, EVs transfer biological information to surrounding cells and contribute not only to physiological functions but also to the pathogenesis of some diseases, such as cancers. Therefore, a better understanding of cell-to-cell interactions may lead to identification of potential therapeutic targets. Recent reports have suggested that EVs are evolutionarily conserved constitutive mediators that regulate hematopoiesis. Here, we focus on the emerging roles of EVs in normal and pathological conditions, particularly in hematological malignancies. Owing to the high abundance of EVs in biological fluids, their potential use as biomarkers and therapeutic tools is discussed.

Investigation the apoptotic effect of silver nanoparticles (Ag-NPs) on MDA-MB 231 breast cancer epithelial cells via signaling pathways.

Background: The discovery of novel cancer therapeutic strategies leads to the development of nanotechnology-based methods for cancer treatment. Silver nanoparticles (Ag-NPs) have garnered considerable interest owing to their size, shape, and capacity to modify chemical, optical, and photonic properties. This study aimed to investigate the impact of Ag-NPs on inducing of apoptosis in MDA-MB 231 cells by examining specific signaling pathways. Materials and methods: The cytotoxicity of Ag-NPs was determined using an MTT assay in MDA-MB 231 cells. The apoptotic effects were assessed using the Annexin-V/PI assay. Real-time PCR and western blotting were conducted to analyze the expression of apoptosis-related genes and proteins, respectively. Levels of ERK1/2 and cyclin D1 were measured using ELISA. Cell cycle assay was determined by flow cytometry. Cell migration was evaluated by scratch assay. Results: The results revealed that Ag-NPs triggered apoptosis and cell cycle arrest in MDA-MB 231 cells. The expression level of Bax (pro-apoptotic gene) was increased, while Bcl-2 (anti-apoptotic gene) expression was decreased. Increased apoptosis was correlated with increased levels of p53 and PTEN. Additionally, notable alterations were observed in protein expression related to the Janus kinase/Signal transducers (JAK/STAT) pathway, including p-AKT. Additionally, reduced expression of h-TERT was observed following exposure to Ag-NPs. ELISA results demonstrated a significant reduction in p-ERK/Total ERK and cyclin D1 levels in Ag-NPs-exposed MDA-MB 231 cells. Western blotting analysis also confirmed the reduction of p-ERK/Total ERK and cyclin D1. Decreased level of cyclin D is associated with suppression of cell cycle progression. The migratory ability of MDA-MB-231 cells was reduced upon treatment with Ag-NPs. Conclusions: Our findings revealed that Ag-NPs influenced the proliferation, apoptosis, cell cycle, and migration in MDA-MB 231 cells, possibly by modulating protein expression of the AKT/ERK/Cyclin D1 axis.

The link between seizures and prolactin: A study on the effects of anticonvulsant medications on hyperprolactinemia in rats.

Seizures are a common neurological disorder that affects people of all ages. These sudden, uncontrolled electrical disturbances in the brain can cause a variety of symptoms, including convulsions, loss of consciousness, and abnormal sensations. While seizures have long been recognized as a potential cause of hormonal imbalances, recent research has shed new light on the link between seizures and prolactin. The study involved 30 adult female Wistar rats, which were divided into a control group (treated with normal saline) and four treatment groups: chronic group (treated with 30 mg/kg pentylenetetrazol intraperitoneally three days a week for 10 weeks), chronic + Levetiracetam (50 mg/kg, gavage), chronic + Cabergoline (0.05 mg/kg, gavage), and chronic + Levetiracetam (25 mg/kg) + cabergoline (0.025). The drugs were administered three days a week for 10 weeks. Field action potentials were recorded from the CA1 area of the hippocampus using eLab after anesthetizing the animals with a ketamine-xylazine combination (70 +7 mg/kg). The prolactin levels were measured using the ELISA method after serum preparation. The findings indicate that the use of levetiracetam as an anticonvulsant drug resulted in a significant decrease in the amount of prolactin and spike number of convulsive activities compared to the chronic group. However, the amplitudes of convulsive activities did not show a significant difference between the control and other treatment groups. In conclusion, investigating the possibility of subclinical seizures and utilizing anticonvulsant medications in hyperprolactinemia that is resistant to treatment are crucial in treating infertility.

Targeting the stem cell niche micro-environment as therapeutic strategies in aging.

Adult stem cells (ASCs) reside throughout the body and support various tissue. Owing to their self-renewal capacity and differentiation potential, ASCs have the potential to be used in regenerative medicine. Their survival, quiescence, and activation are influenced by specific signals within their microenvironment or niche. In better words, the stem cell function is significantly influenced by various extrinsic signals derived from the niche. The stem cell niche is a complex and dynamic network surrounding stem cells that plays a crucial role in maintaining stemness. Studies on stem cell niche have suggested that aged niche contributes to the decline in stem cell function. Notably, functional loss of stem cells is highly associated with aging and age-related disorders. The stem cell niche is comprised of complex interactions between multiple cell types. Over the years, essential aspects of the stem cell niche have been revealed, including cell-cell contact, extracellular matrix interaction, soluble signaling factors, and biochemical and biophysical signals. Any alteration in the stem cell niche causes cell damage and affects the regenerative properties of the stem cells. A pristine stem cell niche might be essential for the proper functioning of stem cells and the maintenance of tissue homeostasis. In this regard, niche-targeted interventions may alleviate problems associated with aging in stem cell behavior. The purpose of this perspective is to discuss recent findings in the field of stem cell aging, heterogeneity of stem cell niches, and impact of age-related changes on stem cell behavior. We further focused on how the niche affects stem cells in homeostasis, aging, and the progression of malignant diseases. Finally, we detail the therapeutic strategies for tissue repair, with a particular emphasis on aging.

Adipose Tissue-Mesenchymal Stem Cells Caused to Change the Methylation Status of hTERT Gene Promoter CpG Islands of Molt-4 Leukemia Cells as Cell-based Therapy.

BACKGROUND: DNA methylation was considered as prognostic information in some hematological malignancies. Previous studies have reported the in vitro and in vivo biology role of mesenchymal stem cells (MSCs) on leukemic cells. The aim of this study was to investigate the effect of MSCs on the promoter methylation status of hTERT as a catalytic subunit of telomerase enzyme. METHODS: In the experimental study, the Molt-4 leukemic cells were co-cultured with MSCs for 7 days. At the end of the co-culture period, the Molt-4 cells were collected, DNA and protein were extracted. Then methylation specific-PCR and western blotting were done for evaluating the hTERT gene promoter methylation status and cyclin D1 and hTERT protein expression, respectively. In the following, the flow cytometry was done for cell cycle distribution assay. RESULTS: It was found that MSCs resulted in a significant decrease in the cyclin D1 and hTERT protein expression levels. Also, MSCs caused changes in the methylation status of the CpG islands in the hTERT gene promoter region. The following results showed that MSCs caused a significant increase in the number of cells at G0/G1 phase and arrest the G0/G1 phase as well as decrease in the cell proliferation of Molt-4 cells. CONCLUSION: It is concluded that co-culture of MSCs with Molt-4 cells could be involved in changing the methylation status of hTERT gene promoter, cell cycle and hTERT protein expression; it could be potentially beneficial for further investigations regarding the cell transplantation and cell-based therapy.

The effects of encapsulation on NK cell differentiation potency of C-kit+ hematopoietic stem cells via identifying cytokine profiles.

Natural killer cells (NK cells) can kill cancerous cells without prior sensitization. This feature makes them appealing candidates for cellular therapy. Due to the degradation rate and controlled release of these matrices, hydrogels hold great promise in cell differentiation. The study aims to investigate the effect of encapsulated alginate-gelatin on the differentiation potential of C-kit+ cells toward NK cells which are mediated by cytokines detection. Under both encapsulated and unencapsulated conditions, C-kit+ cells can differentiate into NK cells. In the following, real-time PCR and western blotting were done to investigate the mRNA and protein expression, respectively. Determine cytokine profiles from the collected culture medium conducted a Cytokine antibody array. The differentiated cells were then co-cultured with Molt-4 cells to examine the expression levels of INF-γ, TNF-α, and IL-10 using real-time-PCR. There was a substantial change in protein expression of the Notch pathway. Also, the encapsulation increased the mRNA expression of INF-γ and TNF-α in Molt-4 cells. Based on these findings, the encapsulation effects on the differentiation of C-kit+ cells toward NK cells could be related to the secreted cytokines such as interleukin-10 and INF-γ and the Notch protein expression.

Granulocyte differentiation of rat bone marrow resident C-kit+ hematopoietic stem cells induced by mesenchymal stem cells could be considered as new option in cell-based therapy.

Mesenchymal stem cells (MSCs) are effective in hematopoietic engraftment and tissue repair in stem cell transplantation. In addition, these cells control the process of hematopoiesis by secreting growth factors and cytokines. The aim of the present study is to investigate the effect of rat bone marrow (BM)-derived MSCs on the granulocyte differentiation of rat BM-resident C-kit+ hematopoietic stem cells (HSCs). The mononuclear cells were collected from rat BM using density gradient centrifugation and MSCs and C-kit+ HSCs were isolated. Then, cells were divided into two groups and differentiated into granulocytes; C-kit+ HSCs alone (control group) and co-cultured C-kit+ HSCs with MSCs (experimental group). Subsequently, the granulocyte-differentiated cells were collected and subjected to real-time PCR and Western blotting for the assessment of their telomere length (TL) and protein expressions, respectively. Afterwards, culture medium was collected to measure cytokine levels. CD34, CD16, CD11b, and CD18 granulocyte markers expression levels were significantly increased in the experimental group compared to the control group. A significant change was also observed in the protein expression of Wnt and ß-catenin. In addition, MSCs caused an increase in the TL of granulocyte-differentiated cells. MSCs could affect the granulocyte differentiation of C-kit+ HSCs via increasing TL and Wnt/ß-catenin protein expression.

Investigation of L-carnitine effects on CD44+ cancer stem cells from MDA-MB-231 breast cancer cell line as anti-cancer therapy.

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells, capable of metastasis, recurrence, and drug resistance in breast cancer patients. Therefore, targeting BCSCs appears to be a promising strategy for the treatment and prevention of breast cancer metastasis. Mounting evidence supports the fact that carnitine, a potent antioxidant, modulates various mechanisms by enhancing cellular respiration, inducing apoptosis, and reducing proliferation and inflammatory responses in tumor cells. The objective of this study was to investigate the impact of L-carnitine (LC) on the rate of proliferation and induction of apoptosis in CD44+ CSCs. To achieve this, the CD44+ cells were enriched using the Magnetic-activated cell sorting (MACS) isolation method, followed by treatment with LC at various concentrations. Flow cytometry analysis was used to determine cell apoptosis and proliferation, and western blotting was performed to detect the expression levels of proteins. Treatment with LC resulted in a significant decrease in the levels of p-JAK2, p-STAT3, Leptin receptor, and components of the leptin pathway. Moreover, CD44+ CSCs-treated cells with LC exhibited a reduction in the proliferation rate, accompanied by an increase in the percentage of apoptotic cells. Hence, it was concluded that LC could potentially influence the proliferation and apoptosis of CD44+ CSC by modulating the expression levels of specific protein.

Oxidative stress regulation and related metabolic pathways in epithelial-mesenchymal transition of breast cancer stem cells.

Epithelial-mesenchymal transition (EMT) is a cell remodeling process in which epithelial cells undergo a reversible phenotype switch via the loss of adhesion capacity and acquisition of mesenchymal characteristics. In other words, EMT activation can increase invasiveness and metastatic properties, and prevent the sensitivity of tumor cells to chemotherapeutics, as mesenchymal cells have a higher resistance to chemotherapy and immunotherapy. EMT is orchestrated by a complex and multifactorial network, often linked to episodic, transient, or partial events. A variety of factors have been implicated in EMT development. Based on this concept, multiple metabolic pathways and master transcription factors, such as Snail, Twist, and ZEB, can drive the EMT. Emerging evidence suggests that oxidative stress plays a significant role in EMT induction. One emerging theory is that reducing mitochondrial-derived reactive oxygen species production may contribute to EMT development. This review describes how metabolic pathways and transcription factors are linked to EMT induction and addresses the involvement of signaling pathways.

Synergistic effect of chrysin and radiotherapy against triple-negative breast cancer (TNBC) cell lines.

PURPOSE: Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 20% of cases. Due to the lack of a molecular target, limited options are available for TNBC treatment. Radiation therapy (RT) is a treatment modality for the management of TNBC following surgery; however, it has a detrimental effect on surrounding healthy tissues/cells at a higher rate. METHODS: We examined the effect of RT in combination with chrysin as a possible radiosensitizing agent in an MDA-MB-231 cell line as a model of a TNBC. The growth inhibitory effects of chrysin were examined using an MTT assay. Flow cytometry was performed to evaluate apoptosis and expression of hypoxia-induced factor-1α (HIF-1α). The protein expression of p-STAT3/STAT3 and Cyclin D1 was examined using western blotting. Real-time PCR determined apoptotic-related genes (Bax, BCL2, p53). RESULTS: Treatment of MDA-MB-231 cells with chrysin in combination with RT caused synergistic antitumor effects, with an optimum combination index (CI) of 0.495. Our results indicated that chrysin synergistically potentiated RT-induced apoptosis in MDA-MB-231 compared with monotherapies (chrysin and/or RT alone). Expression of HIF-1α was decreased in the cells exposed to combinational therapy. The apoptotic effect of combinational therapy was correlated with increased Bax (pro-apoptotic gene) and p53 levels along with reduced expression of Bcl-2 (anti-apoptotic gene). Increased apoptosis was associated with reduced expression of Cyclin D1, p-STAT3. CONCLUSION: These findings highlight the potential effect of chrysin as a radiosensitizer, indicating the synergistic anti-cancer effect of chrysin and RT in TNBC. Further investigation is warranted in this regard.

L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways.

BACKGROUND: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components. METHODS: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively. RESULTS: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway. CONCLUSION: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

Cellular and Molecular Mechanisms Involved in Hematopoietic Stem Cell Aging as a Clinical Prospect.

There is a hot topic in stem cell research to investigate the process of hematopoietic stem cell (HSC) aging characterized by decreased self-renewal ability, myeloid-biased differentiation, impaired homing, and other abnormalities related to hematopoietic repair function. It is of crucial importance that HSCs preserve self-renewal and differentiation ability to maintain hematopoiesis under homeostatic states over time. Although HSC numbers increase with age in both mice and humans, this cannot compensate for functional defects of aged HSCs. The underlying mechanisms regarding HSC aging have been studied from various perspectives, but the exact molecular events remain unclear. Several cell-intrinsic and cell-extrinsic factors contribute to HSC aging including DNA damage responses, reactive oxygen species (ROS), altered epigenetic profiling, polarity, metabolic alterations, impaired autophagy, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, nuclear factor- (NF-) κB pathway, mTOR pathway, transforming growth factor-beta (TGF-ß) pathway, and wingless-related integration site (Wnt) pathway. To determine how deficient HSCs develop during aging, we provide an overview of different hallmarks, age-related signaling pathways, and epigenetic modifications in young and aged HSCs. Knowing how such changes occur and progress will help researchers to develop medications and promote the quality of life for the elderly and possibly alleviate age-associated hematopoietic disorders. The present review is aimed at discussing the latest advancements of HSC aging and the role of HSC-intrinsic factors and related events of a bone marrow niche during HSC aging.

Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor- Mesenchymal Stem Cell Interaction for Therapeutic Interventions.

Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

An Overview of Autophagy in Hematopoietic Stem Cell Transplantation.

Autophagy is a fundamental homeostatic process crucial for cellular adaptation in response to metabolic stress. Autophagy exerts its effect through degrading intracellular components and recycling them to produce macromolecular precursors and energy. This physiological process contributes to cellular development, maintenance of cellular/tissue homeostasis, immune system regulation, and human disease. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only preferred therapy for most bone marrow-derived cancers. Unfortunately, HSCT can result in several serious and sometimes untreatable conditions due to graft-versus-host disease (GVHD), graft failure, and infection. These are the major cause of morbidity and mortality in patients receiving the transplant. During the last decade, autophagy has gained a considerable understanding of its role in various diseases and cellular processes. In light of recent research, it has been confirmed that autophagy plays a crucial role in the survival and function of hematopoietic stem cells (HSCs), T-cell differentiation, antigen presentation, and responsiveness to cytokine stimulation. Despite the importance of these events to HSCT, the role of autophagy in HSCT as a whole remains relatively ambiguous. As a result of the growing use of autophagy-modulating agents in the clinic, it is imperative to understand how autophagy functions in allogeneic HSCT. The purpose of this literature review is to elucidate the established and implicated roles of autophagy in HSCT, identifying this pathway as a potential therapeutic target for improving transplant outcomes.

Mesenchymal stem cells cause induction of granulocyte differentiation of rat bone marrow C-kit+ hematopoietic stem cells through JAK3/STAT3, ERK, and PI3K signaling pathways.

Objectives: Hematopoietic stem cells (HSCs) are the cells that give rise to different types of blood cells during the hematopoiesis process. Mesenchymal stromal cells (MSCs) as key elements in the bone marrow (BM) niche interact with hematopoietic progenitor cells (HPCs) by secreting cytokines, which control HPCs maintenance and fate. Here we report that BM-MSCs are capable of inducing granulocytic differentiation of the C-Kit+ HSCs via activating JAK3/STAT3, ERK, and PI3K signaling pathways. Materials and Methods: For this purpose, BM-MSCs and C-kit+ HSCs were isolated. Next, cells were divided into two groups and differentiated into granulocytes: C-kit+ HSCs alone (control group) and co-cultured C-kit+ HSCs with MSCs (experimental group). Afterward, the gene and protein expression were assessed by real-time PCR and western blotting, respectively. Results: It was found that BM-MSCs resulted in increased JAK3/STAT3, ERK, and PI3K protein expression in granulocyte differentiated C-kit+ HSCs. Conclusion: It should be concluded that MSCs could affect the granulocyte differentiation of C-kit+ HSCs via increasing JAK3/STAT3, ERK, and PI3K signaling pathways.