Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review

Immunotherapy employing natural killer (NK) cells has emerged as a transformative approach to treating hematological malignancies. The reprogramming of NK cells by incorporating a chimeric antigen receptor (CAR) equipped with potent signaling domains has demonstrated efficacy in enhancing NK cell responses and improving specificity in recognizing cancerous cells. Despite these advancements, the primary challenge in implementing allogeneic NK cell therapy requiring a viable donor source for clinically relevant doses remains unresolved. This study tested NK cells obtained from leukoreduction filters (LRF) post-blood donation to address the need for an efficient and scalable supply of NK cells for generating anti-BCMA CAR NK cells. LRF-NK cells were isolated under sterile conditions and compared with peripheral blood (PB)-derived NK cells in terms of immunophenotype, proliferation capacity, and functional characteristics. Notably, no significant differences in inherent characteristics were observed between LRF-NK and PB-NK cells. Subsequently, both NK cell populations were employed to generate anti-BCMA CAR-NK cells. The data revealed a high specific cytotoxicity of Anti-BCMA CAR LRF-NK cells during co-culture with U266-B1 cells (70.3 ± 4.78%), surpassing that observed with CCRF-CEM cells (31.3 ± 2.35%) and similar to Anti-BCMA CAR PB-NK cells. Furthermore, the expression of IFN-γ and Granzyme B, following the co-culture of Anti-BCMA CAR LRF-NK cells with target cells, mirrored that observed in Anti-BCMA CAR PB-NK cells. This study provides the rationale and feasibility of utilizing LRF-NK cells as a safe, high-yield, accessible, and optimal cost-effective source for cancer immunotherapy.

Background: Extracellular vesicles are particles ranged from 30 nm to 5μm and subcategorized into three groups; exosomes, microvesicles and apoptotic bodies, each of which have different biological impact. Lack of a standard method for the detection and isolation of MVs has led to a challenging issue that is a worth considering. In this study, we isolated MVs from the conditioned medium of UC-MSCs by four different schemes of ultracentrifugation.

Umbilical cord blood-derived mesenchymal stromal cells (UCB-MSCs) are ideally suited for use in various cell-based therapies. We investigated a novel induction protocol (NIP) to improve the neuronal differentiation of human UCB-MSCs under appropriate conditions. This experimental study was performed in Iranian Blood Transfusion Organization (IBTO), Tehran, Iran. UCB-MSCs were cultured in DMEM medium supplemented with 10% FBS in a humidified incubator in equilibration with 5% CO2 at 37°C. For neuronal differentiation of UCB-MSCs, DMEM was removed and replaced with pre-induction medium containing RA, bFGF, EGF, and basal medium for two days. Then, NGF, IBMX, AsA, and Neurobasal medium were used for six days for this purpose. Real-time PCR was performed to analyze the neuronal differentiation of UCB-MSCs for the first time in Iran. We found that the maximum and minimum levels of gene expression were related to GFAP and nestin, respectively. In addition, our study showed that compared to other neuronal inducers, RA might play the main role in neuronal differentiation and fate of MSCs compared to other neuronal inducers. Our data showed that the combination of chemical (RA, IBMX, AsA) and growth factors (NGF, EGF, bFGF) in NIP may improve the efficiency of neuronal differentiation of UCB-MSCs and may provide a new method for easy and quick application of UCB-MSCs in regenerative medicine in the future. However, the functionality of neuron-like cells must be carefully assessed in animal experiments prior to use in clinical applications.