forms are treated by a radical cystectomy, which consists in removing the entire bladder but sometimes also the surrounding tissues (6). It should be noted that recurrences after treatment will occur in 80% of non-invasive BCa cases, which can then progress to an invasive form in 30% of patients (7). In the last three decades, no significant improvement resulted from research to reduce the mortality of the BCa. Immunotherapy has recently raised hopes, but the results still seem limited, even if they may in the future
Spinal cord injury (SCI) is damage to the spinal cord due to trauma or health conditions, resulting in lesions in the spinal cord. Currently, available treatment includes surgical intervention to decompress or stabilize a dislocated loose spine, steroid drugs to reduce inflammation, and subsequent rehabilitation. As there is a rising number of SCI globally, radical treatments to recover spinal cord functions have become highly anticipated. The development of new treatments is indeed progressing. Various therapeutic drug candidates are being developed in clinical trials, including neuroprotective/neurotrophic factors, antibodies for repulsive guidance molecules, and cell transplantation. Among them, with advances in stem cell biology, cell transplantation therapy is currently a promising therapeutic development for SCI. In particular, there have been various reports regarding the realization of regenerative medicine using human induced pluripotent stem cells (iPSCs). This review will introduce the advantages of cell-based therapy based on iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs) and some of their mechanisms of action for functional improvement, which have recently been elucidated. Potential challenges and methodologies to realize the clinical application of iPSC-NS/PCs not only for the subacute phase but also for the chronic phase of SCI will be presented. Finally, we also introduce recent research with a view to the clinical application of spinal cord regenerative therapy and discuss future prospects.
Background:Cell-based therapies are promising for tolerance induction in bone marrow (BM), solid organs, and vascularized composite allotransplantation (VCA). The toxicity of bone marrow transplantation (BMT) protocols precludes this approach from routine clinical applications. To address this problem, we developed a new therapy of Human Umbilical Di-Chimeric (HUDC) cells for tolerance induction in transplantation. This study established in vitro characterization of the created HUDC cells.Methods:We performed sixteen ex vivo polyethylene glycol (PEG)-mediated fusions of human umbilical cord blood (UCB) cells from two unrelated donors. Fusion feasibility was confirmed in vitro by flow cytometry (FC) and confocal microscopy (CM). The HUDC cells' genotype was assessed by lymphocytotoxicity test and short tandem repeat-polymerase chain reaction (STR-PCR) analysis, phenotype by FC, viability by LIVE/DEAD® assay, and apoptosis level by Annexin V staining. We used COMET assay to assess HUDC cells' genotoxicity after the fusion procedure. Clonogenic properties of HUDC cells were evaluated by colony forming unit (CFU) assay. Mixed lymphocyte reaction (MLR) assay assessed immunogenic and tolerogenic properties of HUDC cells.Results:We confirmed the creation of HUDC cells from two unrelated human donors of UCB cells by FC and CM. Human leukocyte antigen (HLA) class I and II typing, and STR-PCR analysis of HUDC cells confirmed the presence of alleles and loci from both unrelated UCB donors (donor chimerism: 49%±8.3%, n=4). FC confirmed the hematopoietic phenotype of HUDC cells. We confirmed high HUDC cells' viability (0.47% of dead cells) and a low apoptosis level of fused HUDC cells (15.9%) compared to positive control of PKH-stained UCB cells (20.4%) before fusion. COMET assay of HUDC cells revealed a lack of DNA damage. CFU assay confirmed clonogenic properties of HUDC cells, and MLR assay revealed a low immunogenicity of HUDC cells.Conclusions:This study confirmed creation of a novel HUDC cell line by ex vivo PEG-mediated fusion of UCB cells from two unrelated donors. The unique concept of creating a HUDC cell line, representing the genotype and phenotype of both, transplant donor and the recipient, introduces a promising approach for tolerance induction in BM, solid organs, and VCA transplantation.
