Objective: This study aimed to elucidate the effects of melanoma-derived exosomes on modulating the differentiation of hematopoietic stem cells (HSCs) towards immunosuppressive myeloid-derived suppressor cells (MDSCs). Materials and Methods: Exosomes were isolated via ultracentrifugation from conditioned media of the B16F10 murine melanoma cell line after adaptation to exosome-free culture conditions. HSCs were extracted from the bone marrow of adult C57BL/6 mice through density gradient separation and MACS column isolation of CD133+ and CD34+ populations. HSCs were cultured with or without B16F10 exosomes for 24 hours. Flow cytometry analyzed the expression of canonical MDSC surface markers CD11b, Ly6G, and Ly6C. Levels of the immunosuppressive cytokines interleukin-10 (IL-10) and tumor necrosis factor beta (TGF-β) in HSC culture supernatants were quantified by ELISA. Results: Compared to untreated controls, HSCs treated with B16F10 exosomes displayed significantly increased percentages of CD11b+Ly6G+ granulocytic MDSCs and CD11b+Ly6C+ monocytic MDSCs, with a notable predominance of the Ly6G+ granulocytic subtype. Additionally, exosome-treated HSCs secreted markedly higher levels of the cytokines IL-10 and TGF-β, which are involved in MDSC-mediated immunosuppression. Conclusions: Our findings demonstrate that melanoma-derived exosomes can orchestrate the differentiation of HSCs into MDSCs with an immunosuppressive phenotype, as evidenced by the upregulation of MDSC surface markers and secreted cytokines. This supports a role for tumor-derived exosomes in driving the systemic expansion and accumulation of immunosuppressive MDSCs through the reprogramming of HSC fate. Elucidating the exosome contents and HSC signaling pathways involved could reveal therapeutic strategies to block this pathway and enhance anti-tumor immunity.
The skin is the largest organ in the human body and plays a significant role in protecting the body from external threats, containing tissues that sustain the body's homeostasis. Wound healing in the skin is a complex process involving the interaction of various cell types in the target tissue, including but not limited to cytokines and growth factors. In extreme cases, disorders of the cardiorespiratory system, such as chronic diseases, may prevent the process of wound healing entirely. Numerous studies have been conducted to discover methods to restore the ability of chronic wounds to cure themselves, but this remains one of the most significant medical problems. Exosomes derived from stem cells have been extensively proposed as a treatment for dermal wound recovery. Different types of stem cells have varying therapeutic potential. Exosomes, a component of paracrine, have the function of enhancing the effectiveness of stem cells. This article discusses the wound healing process as well as the mechanism of stem cell and adipose-derived exosome therapy on cutaneous wound healing and its clinical applications.
Colorectal cancer (CRC) treatment using common chemotherapy approaches has drawbacks such as side effects, costs, and resistance of cancer cells which affects patients’ prolonged survival, and quality of life. The immune cells have pivotal roles in regulating tumor progression in the tumor microenvironment (TME). The most important CRC cellular immunotherapies include the use of tumor-derived cells such as tumor-infiltrating lymphocytes (TILs) and lymph node lymphocytes (LNLs), peripheral blood mononuclear cells (PBMCs), derived cells, including T cells, natural killer (NK) cells, cytokine-induced killer (CIK) cells, and chimeric antigen receptor (CAR) cells. Although adoptive cell therapy has some advantages, some disadvantages have been reported. TILs cells are strictly directed against tumor-specific antigens; however, they are inefficient due to immune editing. CIK cells have a major histocompatibility complex (MHC)-independent cytotoxic effect and need concurrent high-dose interleukin (IL)-2 administration. In addition, chimeric antigen receptor-T cells (CAR-T cells) are MHC-independent that overcome MHC downregulation by the tumor. They are potent in recognizing any cell surface antigen and are applicable to a broad range of patients and T-cell populations. Here, the researchers present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance by referring to data obtained from CRC clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy intervention, in combination with other treatments like chemotherapy, radiotherapy, and targeted therapy, is promising for cancer therapy.
BACKGROUND: The aim of this case study was to investigate the safety and efficacy of the SONG Laser Protocol in the context of dementia. Our hypothesis is that the SONG Laser Protocol, when administered intravenously, may have a beneficial effect on the alpha waves [as assessed by electroencephalography (EEG)] in a patient suffering from dementia. CASE REPORT: This was a case study focusing on a single patient suffering from dementia. The SONG Laser Protocol was delivered in a clinical setting, and the primary outcome measures were the amplitude of alpha waves as seen in EEG, the target frequency of the alpha waves, and the power spectrum density. The pre- and post-SONG Laser Protocol EEGs were compared. A clear increase in alpha wave activity on Day 3 post-SONG Laser Protocol was detected. The alpha wave target frequency increased to 8.0 (normal range 8.0-12.0), and the power spectrum density (PSD) increased by 65%. The patient also expressed feelings of improved well-being following the SONG Laser Protocol. CONCLUSIONS: The SONG Laser Protocol may have a beneficial effect on alpha wave activity in a patient suffering from dementia. Clinical trials are needed to confirm safety and efficacy.
Modeling the human brain in order to study its physiology, development and diseases has been very challenging due to its structural and functional complexity and fragility. Brain organoids, derived from human pluripotent stem cells, opened a new approach to create in vitro 3D models, that more closely resemble the complexity of the brain, as compared to 2D cell cultures. So far, multiple developmental and neurodegenerative diseases have been generated with organoid technology and used as drug screening platforms not only to accelerate the development of more efficient treatments but also to get one step closer to personalized medicine. This review aims to showcase the current applications of brain organoids and review future perspectives and limitations.
