Masoud Soleimani

Monocytes and their differentiated counterparts, M1 macrophages, are critical players in regenerative medicine. Various sources provide monocytes for therapeutic and research purposes, each with distinct advantages and limitations. Umbilical cord blood (UCB) is a promising noninvasive source of monocytes, offering high purity and yield and unique immunological properties that enhance its therapeutic potential. However, the challenges of monocyte isolation and differentiation necessitate optimized methodologies for practical use. This study presents a refined protocol for isolating monocytes from UCB using a five-step gradient centrifugation method, followed by their differentiation into M1 macrophages through cytokine stimulation. The protocol includes erythrocyte sedimentation, mononuclear cell isolation via Ficoll-Paque gradient centrifugation, cold-aggregation purification, adherence selection, and macrophage differentiation via stimulation with GM-CSF, IFN-γ, and LPS. Flow cytometric analysis confirmed high monocyte purity, elevated CD14 and CD45 expression, and minimal contamination from lymphocytes and other immune cells. Differentiated macrophages exhibited increased expression of M1 markers, including CD80 and CD86, and reduced expression of M2-associated markers, confirming successful polarization. This study underscores the feasibility of using UCB-derived monocytes as a viable alternative to traditional sources, with advantages in accessibility, purity, and immunomodulatory potential. The refined isolation and differentiation approach offers a standardized method for generating phenotypically M1 macrophages, facilitating their application in regenerative medicine, immune modulation, and neuroprotection.

Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection, strongly associated with chronic inflammation and cervical cancer progression in women. Persistent HPV infection leads to an inflammatory microenvironment that promotes epithelial dysplasia and immune evasion. Exosomes derived from mesenchymal stem cells (MSC‐exosomes) have emerged as promising immunomodulatory and anti‐inflammatory agents. This review examines current evidence on the interaction between HPV‐induced inflammation and exosomal signaling, with a particular focus on the therapeutic potential of MSC‐exosomes. We discuss their roles in immune regulation, miRNA delivery, suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling, and epithelial regeneration. This anti‐inflammatory effect may also impair local immune surveillance, potentially enabling viral persistence and progression to malignancy. In this narrative review, We reviewed PubMed, Scopus, and Web of Science articles published up to 2024 on MSC‐exosome interactions with immune regulation in HPV‐related diseases. Evidence suggests that while the anti‐inflammatory effects of MSC‐exosomes may help control HPV‐associated inflammation, they can also impair local immune surveillance, potentially facilitating viral persistence and progression toward malignancy. This dual activity positions MSC‐exosomes as a double‐edged sword in the context of HPV pathogenesis. A deeper understanding of this paradox is essential for designing safer, context‐specific MSC‐based therapies that balance anti‐inflammatory benefits with effective antiviral immune responses. Although direct studies on MSC‐exosomes in HPV infections are limited, existing models suggest that they have the capacity to attenuate inflammation and restore cervical tissue homeostasis. This article also highlights knowledge gaps and future research directions necessary to develop MSC‐exosome‐based therapies for HPV‐related cervical diseases.

Predominantly a widespread beta herpesvirus, human cytomegalovirus (HCMV) triggers lifelong latent infection in most of the people, and HCMV vaccine development has been designated a high public health priority. In the current study, the in vitro safety profile and potential immunotoxic effects of a novel messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine designed against human cytomegalovirus (HCMV) were assessed. The aim was to measure inflammation, allergic reactions, complement activation, cytotoxicity, and hemolytic effects of the mRNA-LNP vaccine. Proinflammatory cytokine secretion, evident in human peripheral blood mononuclear cells (hPBMCs) treated with unmodified mRNA-LNP, was markedly attenuated by incorporating modified nucleotides. The vaccine appeared incapable of sparking allergic cytokine production or complement activation. Cell viability assays indicated no pronounced cytotoxicity, and hemolysis assays showed no notable hemolytic activity. The findings suggest that the modified mRNA-LNP vaccine exhibits a promising in vitro safety profile, supporting further development of this vaccine candidate.

This study aimed to investigate the feasibility of using engineered NK-92 cell-derived exosomes to deliver miR-124 to breast cancer cell lines and to assess the anti-tumor effects of these exosomes in breast cancer cell lines. In this study, the NK-92 cell line was genetically engineered to overexpress miR-124. Subsequently, exosomes were isolated from the modified cell line. The effects of these NK-92-miR-124 exosomes were assessed on the proliferation, apoptosis, and migration of three different subtypes of breast cancer cell lines (MCF-7, MDA-MB-231, and SK-BR-3) using MTT assays, Annexin V/PI staining, and scratch tests, respectively. Finally, the results from all experiments were compared with the outcomes obtained from the treatment of breast cancer cell lines with NK-92 exosomes. All comparisons were made under the same experimental conditions. Our findings demonstrated that miR-124 was effectively delivered to breast cancer cell lines via engineered NK-92-derived exosomes. Furthermore, these NK-92-miR-124-loaded exosomes exhibited notable anti-tumor effects, such as reducing cell proliferation and migration across all three breast cancer cell lines. Additionally, they significantly enhanced apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines compared to NK-92-derived exosomes. Our study demonstrated that engineered NK-92-derived exosomes can effectively deliver miR-124 to breast cancer cells, leading to reduced migration and enhanced apoptosis. However, the anti-tumor effects varied among different breast cancer cell lines.

Diffuse large B cell lymphoma (DLBCL) is one of the most aggressive hematological diseases. Angiogenesis is one of the important aspects of DLBCL, providing the basics for tumor growth and metastasis. In this review, we discussed the Vascular Endothelial Growth Factor (VEGF) polymorphisms, the role of VEGF expression and angiogenesis in disease pathophysiology, and the association of VEGF and other angiogenesis parameters in the prognosis of this non-Hodgkin lymphoma. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies related to VEGF and angiogenesis in DLBCL. Keywords included “VEGF,” “angiogenesis,” “DLBCL,” and “anti-angiogenesis therapy.” Relevant articles from the past two decades were prioritized for inclusion. Based on the majority of previous studies, VEGF and the higher score of angiogenesis may play a role in the disease’s aggressiveness. Seemingly, an abnormal vascular network may assist tumor cells in evading the immune system. Regarding improving anti-angiogenesis therapy, it could be considered one member of the combination treatment for DLBCL. The numerous studies highlighting the significance of angiogenesis in lymphoma, yet failing to achieve substantial improvements in patient survival, underscore the need for further research in this field.

Background The success of hematopoietic stem cell transplantation (HSCT) relies significantly on the effective mobilization and collection of hematopoietic stem cells. However, various factors can lead to failure in hematopoietic stem cell mobilization in some patients, including age, type of malignancy, chemotherapy regimens (such as fludarabine, Melphalan, and Lenalidomide), radiotherapy, bone marrow cellularity, and comorbidities. This study investigates the impact of Diabetes Mellitus type 2 on hematopoietic stem cell mobilization outcomes in patients undergoing autologous transplantation. Materials and Methods We conducted a retrospective analysis of 43 patients, comparing mobilization efficiency, engraftment times, and blood product transfusion requirements between diabetic and non-diabetic cohorts. Mobilization was achieved using granulocyte colony-stimulating factor (G-CSF), with the specific dosing regimen and timing of apheresis detailed in the methods section. Results Our findings indicate that diabetic patients exhibited significantly lower CD34 + cell counts and required more engraftment time than their non-diabetic counterparts (P < 0.05). Additionally, diabetic patients had higher rates of blood product transfusions post-transplantation. Conclusion Our findings have shed light on the impact of Diabetes Mellitus type 2 on Hematopoietic Stem Cells mobilization and autologous transplantation, providing crucial insights for the hematopoietic stem cell transplantation field. It is crucial to recognize that diabetes can significantly affect the outcomes of hematopoietic stem cell transplantation. Factors such as poor stem cell mobilization, prolonged engraftment times, and increased need for blood product transfusions underscore the importance of considering diabetes in HSCT candidates.

Acute myeloid leukemia (AML) is an aggressive malignancy with limited treatment options. Enhancing natural killer (NK) cell functionality through artificial antigen-presenting cells (aAPCs) represents a promising immunotherapeutic strategy. This study evaluates the potential of genetically modified K562 cells, expressing CD137L and CD86, to enhance NK cell-mediated cytotoxicity against AML cell lines (HL-60, KG-1, and THP-1). Lentiviral transduction was used to generate aAPCs, confirmed by PCR, RT-PCR, and flow cytometry. Cord NK cells and the NK-92 cell line were co-cultured with aAPCs, and their cytotoxicity against cell lines was assessed using 7-AAD staining. The ability of transduced K562 cells to substitute for interleukin-15 (IL-15) was also evaluated. These cells significantly enhanced NK cell-mediated cytotoxicity, with greater effects observed at higher effector-to-target (E:T) ratios. The aAPCs partially replaced IL-15 in activating cord blood NK cells but were ineffective for NK-92 cells. The aAPCs effectively enhance NK cell cytotoxicity and may reduce cytokine dependence in therapeutic applications. These findings highlight the potential of aAPCs to improve NK cell-based immunotherapies.