Triple-negative breast cancer (TNBC) is a highly aggressive subtype with few treatment options and limited response to radiation therapy due to radioresistance. This study explores the anti-angiogenic and anti-migratory potential of silver nanoparticles (Ag-NPs) as radiosensitizers in TNBC cell lines (MDA-MB-231 and MDA-MB-468). Cells were exposed to Ag-NPs and RT. Cell viability was assessed by MTT and trypan blue exclusion assay. Apoptosis and intracellular reactive oxygen species (ROS) were detected by flow cytometry. Angiogenesis-related genes were evaluated by qPCR, while MMP2 and MMP9 protein levels were determined by western blotting. Cell migration and tube formation were assessed using a scratch assay and an endothelial tube formation assay, respectively. Combination of Ag-NPs with RT exhibited strong synergistic anticancer effects in TNBC cell lines. The combinational treatment significantly enhanced apoptosis and ROS production compared to control and individual treatments. It also reduced VEGFR2 and Tie2 gene expression in both cell lines and decreased MMP2 and MMP9 protein levels in MDA-MB-231 cells. Cell migration and tube formation were significantly impaired in MDA-MB-231 cells exposed to combination therapy. Ag-NPs enhanced the cytotoxic effects of RT in TNBC cell lines by increasing apoptosis and ROS, and suppressing cell migration and angiogenic activity, suggesting their potential as a radiosensitizer to improve therapeutic strategies.

Cancer remains one of the leading causes of mortality worldwide. Among these, hematologic malignancies originating in the bone marrow present unique challenges for in vivo modeling due to their complex pathophysiology and dynamic microenvironment. Over the years, numerous approaches have been developed better to understand cancer initiation, progression, and therapeutic resistance. The advent of three-dimensional (3D) organoid culture has accelerated progress in molecular and cellular oncology by providing physiologically relevant models that recapitulate key aspects of human tissues. Derived from pluripotent stem cells or patient-derived samples, organoids replicate essential structural and functional features of native tissues, thereby enabling detailed investigations of disease progression, immune interactions, and treatment responses. This review outlines the historical development and emerging applications of organoid systems in cancer research. Furthermore, introduce hematologic organoids and how bone marrow (BM), lymph nodes (LNs), thymus, and spleen organoids can replicate the hematologic malignancies for personalized therapies and research studies. Additionally, we highlight the influences of key signaling pathways—including Notch, TGF-β, JAK/STAT, and Hedgehog—in regulating hematopoiesis and leukemogenesis within hematologic organoid platforms. Moreover, advances in co-culture systems that integrate tumor cells with stromal and immune components have provided powerful tools for modeling the hematology tumor microenvironment by enhancing preclinical drug testing and introducing personalized therapeutic strategies. As the field advances, the integration of organoid technology with bioengineering approaches and multi-omics platforms is expected to revolutionize translational research and accelerate the development of novel therapies for hematologic cancers.

The length of a telomere provides insight into the replication history of a cell. Notwithstanding the fact that the telomerase enzyme is produced by stem and progenitor cells, a considerable proportion of the documented telomere degradation takes place at these levels. Sequential transplantation remains a challenge for hematopoietic stem cells (HSCs) transfected with telomerase, despite their ability to maintain telomere length. To optimize stem cell proliferation, additional parameters must be considered [1]. In contrast, unregulated telomere depletion induced by HSCs appears to play a significant role in the pathogenesis of bone marrow failure, as demonstrated by dyskeratosis congenita. It implies that telomerase dysfunction serves as a prevalent ultimate pathogenic mechanism in this heterogeneous hereditary disorder. Although this condition is not well defined, acquired marrow failure syndromes have been linked to mutations in critical telomerase components. In light of the discovery of leukemic stem cells (LSCs) and the desire to develop anti-leukemia treatments for this population, a comprehensive understanding of the telomerase biology within this cell compartment is required. Further research must employ LSC-rich primary samples that have been selected. A more thorough understanding of the correlation between telomere length and telomerase regulation in this specific population may facilitate the creation of innovative approaches or small molecule inhibitors that specifically target the telomerase enzyme complex.

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.

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.

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.

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.

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.

BackgroundThe 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 methodsThe 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.ResultsThe 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.ConclusionsOur 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.

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.

Apple cider vinegar is a fermented compound that contains acetic acid, flavonoids, phenolic compounds, organic acids, minerals, and vitamins. Vitamin A is involved in the development of the immune system and plays regulatory roles in cellular immune responses and humoral immune processes. The aim of this study was to investigate the effect of apple cider vinegar and vitamin A on hematological parameters and immunoglobulin G levels in Gezel lambs. 10 healthy Gazel lambs were used for the study. The lambs were randomly grouped into three groups (control (n = 3), Apple cider vinegar (n = 4), and Vitamin A (n = 3) group). Vitamin A was administrated at a dose of 44,000 IU/kg every ten days for four treatments. ACV was administered orally by drenching (0.5 ml/kg of 6% ACV solution (600 mg ACV), every day, for 40 days). Hematological parameters were determined using standard methods. Total immunoglobulin G concentration was assayed using the turbidimetric immunoassay method. The data obtained before and after drug administration were analyzed by paired T-test and the data of different groups were analyzed using Independent-sample T-test.White blood cells, lymphocytes, and IgG in lambs were significantly increased after administration of Apple cider vinegar (p < 0.05). IgG and lymphocytes were significantly higher in lambs under oral administration of Apple cider vinegar compared to the lambs in the control group (p < 0.05). White blood cells, neutrophils, and IgG were significantly increased in lambs after vitamin A administration (p < 0.05). Neutrophils and IgG were significantly higher in lambs under vitamin A injection compared to the lambs in the control group (p < 0.05). Administration of vitamin A and apple cider vinegar in sheep is safe. They also improve the immune system.

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.

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.

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.

The hormonal protocol is used to increase reproductive efficiency in ewes. The aim of the study was to investigate the effects of 2 prostaglandin F2 alpha (2PGF2 alpha) and compared it with progesterone+ equine chorionic gonadotropin (P4eCG) in nulliparous Ghezel ewes. A total of 132 nulliparous ewes were randomly divided into three groups. The control group (n=42) did not receive any hormonal treatment. The P4eCG group (n=48) used of intravaginal sponge for a 12-day and an injection of 400IU of eCG at the time of sponge removal. The 2PGF2 alpha group (n=42) received the double injection of PGF2 alpha at a 9-day interval. For measurement of the progesterone (P4) concentration, three times (at the start of the experiment, at the time of withdrawal the vaginal sponge and the second injection of PGF(2 alpha) and on days 20 after mating), blood samples were taken from experimental groups ewes. Pregnancy detection was done on the 30-35 days of pregnancy using B-mode ultrasonography. The estrous rate was obtained 100% in all groups. The highest number of nulliparous ewes were in estrus 48 h after the end of the synchronization program (control: 85.8%, 2PGF2 alpha: 85.7%, P4eCG groups: 58.4%). No significant difference was observed in serum P4 concentration at the time 1 and 3 between the groups. The pregnancy and lambing rates were significantly higher (P<0.05) in the P4eCG (85.4% and 85.4%, respectively) and 2PGF(2 alpha) (83.3% and 83.3%, respectively) groups than in the control group (28.6% and 23.8%, respectively). The litter size and twin rates in the P4eCG treatment group (1.19 and 19.5%, respectively) were significantly higher (P<0.05) compared to the 2PGF(2 alpha) (1 and 0%, respectively) and control groups (1 and 0%, respectively). The fecundity rate was no statistically significant difference between the P4eCG (1.02 +/- 0.08) and 2PGF2 alpha (0.83 +/- 0.05) groups (P>0.05). Based on the results, it was concluded that 2PGF2 alpha injection can be employed to synchronize nulliparous estrus ewes in the late breeding season and is a suitable alternative for the P4eCG protocol.

Many studies have shown that bone marrow (BM) stem/progenitor cells have the highest probability of cardiomyocyte differentiation. Regarding the major role of C-kit+ BM stem cells in cell therapy of patients with heart disease and getting cells with higher differentiation potential, this study aimed to investigate the capacity and effect of L-carnitine (LC) on cardiomyogenic differentiation of C-kit+ BM cells through MAPK/ERK signaling pathway. For this purpose, C-kit+ was enriched from the BM mononuclear cell population using a magnetic activating cell sorting technique. The purity of the separated C-kit+ cells was then evaluated by flow cytometry. In the next step, C-Kit+ cells were treated in a cardiomyogenic differentiation culture medium for 21 days once in the presence and once in the absence of 0.2 µM LC (the experimental and control groups). To evaluate the cardiomyogenic differentiation potential of C-kit+ cells, the Desmin cell marker was determined by immunocytochemistry. The expressions of both GATA4 and ERK proteins were measured using western blotting and flow cytometry, respectively. The results show that 95.7 percent of the cells separated by the MACS technique expressed a C-kit+ cell marker. Additionally, it was found that 0.2 mM LC significantly increased the expression of GATA4 protein in the cardiomyogenic differentiated cells. The expression of ERK protein also suggested a significant increase of about 1.60 times in the experimental group in comparison with the control group (*P˂0.05). In brief, it was found that treating C-kit+ BM cells with LC increases cardiomyogenic differentiation by increasing the expression of GATA4. Notably, this effect can take place through MARK/ERK signaling pathway. The results of this research can be valuable in suggesting a treatment solution for cardiovascular diseases.

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.

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 20

Background: Mesenchymal stem cells (MSCs) are undifferentiated cells with the ability of multi-potency, pluripotency, and self-renewal. MSCs show great promise in cancer therapy due to their unique features. MSC secrete various cytokines with multifunctional properties, although their roles are unclear. Methods: We have investigated the influence of secreted cytokines from MSCs on KG-1 cells as a cell model of acute myeloid leukemia (AML). For this purpose, following the culture and characterization of MSCs, a trans-well system was used for co-culturing MSCs and KG-1. To determine apoptosis induction Ki/Caspase-3 assay was conducted for cultured KG-1 alone and in co-culture with MSCs (10:1) on day 7. In the following step, the protein was isolated from both groups (control and experimental) and western blotting was done for investigating the BAX and BCL-2 proteins expression. Results: It was found that MSCs significantly enhanced caspase-3 activity in KG-1 cells (P<0.05). Besides, A significant increase in protein expression of BAX was detected, while BCL-2 displayed a dramatic reduction (P<0.01). Conclusion: As a concluding remark, MSCs have a contributory role in the apoptosis of KG-1 cells that is mediated by Caspase-3, BAX, and BCL2 expression.

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.