Cell Transplantation最新文献

A descriptive qualitative study was conducted to explore risk perception, self-management challenges, and coping strategies among Chinese hematopoietic stem cell transplantation (HSCT) patients, using the Health Action Process Approach (HAPA) as the guiding framework. Purposive sampling, based on the principle of information power, was employed to recruit 20 HSCT patients from a hospital in south-central China between May and August 2024. The HAPA model informed the development of semi-structured interview questions, and the data were analyzed using a combination of thematic analysis and framework analysis. The findings indicate that both risk perception and self-efficacy play a critical role in motivating patient engagement in self-management. Main barriers to self-management included difficulties in symptom control, lifestyle modification, psychological adjustment, and healthcare-related financial burdens. Effective coping strategies reported by participants involved the use of digital tools, seeking professional medical advice, maintaining self-management journals, and drawing on family and social support networks. In clinical practice, healthcare professionals may capitalize on the heightened risk perception and self-efficacy during the peri-transplant period to promote the transition from risk perception to actionable self-management behaviors. In contrast, during the early post-discharge phase, when both risk perception and self-efficacy tend to decline, tailored support systems and resource allocation are helpful for maintaining the transition from risk perception to self-management action.

Posaconazole (POS) tablets were approved for prophylaxis of invasive fungal disease (IFD) in patients with hematological disorders undergoing haploidentical allogeneic stem cell transplantation (haplo-HSCT). There is limited research on drug-drug interactions (DDIs) between POS, cyclosporine A (CsA), and mycophenolate mofetil (MMF), as well as the impact of POS on acute graft versus host disease (aGVHD) in haplo-HSCT patients receiving POS for secondary antifungal prophylaxis (SAP). This study aims to investigate the DDI between POS, CsA, and MMF, as well as the incidence of aGVHD in haplo-HSCT patients with prior-IFD. This is a single-arm, open-label, prospective trial. Plasma concentrations of POS, mycophenolic acid (MPA), and CsA were monitored within 30 days post-transplantation. In addition, the incidences of aGVHD and IFD were observed. Forty-six patients with prior-IFD were enrolled. POS reached a steady state by week 2, with the mean through blood concentration (TBC) of 0.54 ± 0.07 μg/mL. MPA achieved target levels by week 3 without dose adjustment, with a mean TBC of 0.84 ± 0.08 mg/L. The CsA TBC levels required individualized dose modifications. The incidences of grade II-IV and grade III-IV aGVHD were 47.83% and 21.74%, respectively. The breakthrough rate of SAP was 4.35% at 100 days and 10.86% at 6 months. The conclusions indicate that POS tablets do not require dose adjustments for MMF; however, CsA dosing must be individualized. POS tablets appear to be effective and well-tolerated for SAP in haplo-HSCT (the Chinese Clinical Trial Registry: www.chictr.org.cn (ChiCTR2200059472)).

Tubal factor infertility remains a major cause of female reproductive dysfunction. Current therapeutic options, such as surgical repair or in vitro fertilization, only bypass but do not restore the dysfunctional uterine tube. Recent advances in tissue engineering and regenerative medicine (TERM) highlight biomaterials and organoid systems as promising tools to regenerate oviductal tissue and thus support natural conception. The manuscript comprehensively reviews 42 studies focused solely on TERM of the uterine tubes. Current status of uterine tube tissue engineering demonstrates that natural polymers, including collagen and decellularized extracellular matrix, provide biocompatible scaffolds capable of mimicking native extracellular environments. Synthetic polymers enable adjustment of mechanical properties and reproducibility, while hydrogels offer a biomimetic 3D microenvironment that supports epithelial differentiation, angiogenesis, and embryo development. Moreover, uterine tube-derived organoids, in which the polymeric component plays a crucial role, provide physiologically relevant in vitro models for studying pathology, drug testing, and translational applications. Recent advances in 3D bioprinting and magnetic bioprinting have enabled the development of artificial uterine tube models that better mimic native tissue architecture and cell organization. These findings underscore the translational potential of biomaterial-based strategies for uterine tube regeneration. Their integration into reproductive medicine may offer novel therapeutic avenues for restoring tubal function, improving fertility outcomes, and advancing patient-specific approaches in the management of female infertility.

Selective depletion of TCRαβ+ and CD45RA+ subsets of apheresed hematopoietic progenitor cells, HPC(A), enables haploidentical hematopoietic stem cell transplant (haplo-HSCT) by circumventing risks of graft-versus-host disease. Here, we analyze our institution's large series of ex vivo T-cell depletion processes to review procedure performance and explore factors that affect depletion efficiency and graft composition. Over 6 years, 91 haploidentical donors underwent peripheral blood CD34+ stem cell mobilization with granulocyte-colony stimulating factor, with 12 (13%) receiving additional pre-emptive plerixafor. HPC(A) was split into two fractions for TCRαβ and CD45RA depletion with the CliniMACS PLUS device. TCRαβ depletion resulted in a median 4.3 (interquartile range, 4.1-4.5) log reduction, with CD34 recovery at 98% (94%-103%) and TCRγδ+ cell recovery at 89% (74%-98%). CD45RA depletion resulted in a median 4.8 (4.3-5.2) log reduction, with CD3+/CD45RO+ cell recovery at 41% (34%-47%) and CD34 recovery at 58% (51%-68%). TCRαβ depletion efficiency was maintained even when total nucleated cell counts exceeded the maximal specified number, provided the target fraction was within capacity of the depletion kit. Platelet contamination did not affect depletion efficacy or CD34 recovery. Age increases the proportion of CD45RO+ memory cells and TCRαβ subset in HPC(A), while plerixafor increases the latter. Although statistically significant correlation exists between pre-depletion cell composition and depletion performance for some cell subsets, the post-depletion product still met pre-specified threshold without being affected to a clinically relevant extent, over a wide range of input cell numbers. Such robustness of the depletion systems is critical for successful performance of haplo-HSCT.

Patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) are typically placed in a laminar air flow room until hematopoietic reconstitution occurs. In this study, we compared the differences in clinical outcomes between patients receiving allo-HSCT in a conventional laminar flow room (n = 200) and those receiving allo-HSCT in a plasma sterilizer environment (n = 201). The overall infection rates (20.4% vs 25.5%, P = 0.224) and the sites of infection (sepsis, perianal infection, and catheter-related infection) were comparable between the two groups. Additionally, the engraftment times were comparable between the two groups in terms of time to allo-HSCT, leukocyte engraftment time, and platelet engraftment time. The 100-day posttransplantation clinical outcomes were also comparable between the two groups in terms of the probability of overall survival (98.5% vs 99.5%, P = 0.316), leukemia-free survival (96.5% vs 96.5%, P = 0.991), the cumulative incidence of relapse (2.0% vs 3.0%, P = 0.523), non-relapse mortality (1.5% vs 0.5%, P = 0.316) and acute graft-versus-host disease (23.4% vs 22.0%, P = 0.723). Thus, our results demonstrated that receiving allo-HSCT via a plasma sterilizer did not increase the risk of pre-engraftment infection, and the clinical outcomes of these patients were comparable to those of patients in a conventional laminar flow room.

Recent advances in biomedical technologies have extended the boundaries of previously established regulatory guidelines pertaining to stem cell research. These guidelines constrained the study of human pluripotent stem cells (hPSCs) and their derivatives from use under various conditions, including the introduction of hPSCs into the brains of host animals because of concerns of humanizing the brains of animal species. Other guidelines constrained the use of hPSCs in creating human-animal chimeras because of the potential contribution of human stem cells not only to the brain but also to the germline. Some regulatory guidelines forbid the growing of human embryos ex vivo beyond the stage of primitive streak development because of concerns regarding the creation of human forms of life ex vivo. At the subcellular level, there are guidelines regulating the transfer of mitochondria within human embryos. At the molecular level, there are guidelines regulating genome editing to prevent permanent genetic alterations in germline cells. These and other issues related to stem cells have been reviewed, and new research guidelines established by the International Society for Stem Cell Research (ISSCR) for its membership. Because many of the recommended changes by the ISSCR impact research being conducted by members of the American Society for Neural Therapy and Repair (ASNTR), the ASNTR established a task force to review relevant recommendations by the ISSCR to determine which new guidelines to adopt for research conducted by the ASNTR society membership. The final ASNTR recommendations are presented in this document.

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal. They play a critical role in cell therapy due to their powerful immunomodulatory and regenerative effects. Recent studies suggest that one of the key therapeutic mechanisms of MSCs seems to derive from their paracrine product, called extracellular vesicles (EVs). The EVs contain much DNA, messenger RNA (mRNA), microRNA, and protein components, which can exert intracellular communication to target cells. In clinical applications, the MSC-EVs have been widely used in tissue repair and immune disorder diseases. However, there are serval issues need to be considered such as how to accomplish the large-scale production of EVs and how to verify the exact mechanism of EVs. In this review, we summarize the current progress of MSC-EVs and discuss the challenges and future of MSC-EVs.

Diabetic foot ulcers (DFUs) are associated with a high risk of amputations and a 50% 5-year survival rate due at least in part to the limited angiogenic and wound healing capacity of patients with diabetes. Cell therapy via intramuscular injection of peripheral blood mononuclear cells showed encouraging but limited results. Such limitations may arise from the limited ability of therapeutic cells to adhere to the target tissue. The development of a methodology able to support the targeted delivery of viable angiogenic cells would improve cell therapy outcomes in DFU. Here, we optimized a protocol for the production of autologous extracellular matrix (ECM)-rich pericyte-based cell sheets for cell delivery. Pericytes were isolated from skeletal muscle biopsies of DFU patients and non-diabetic controls and characterized by flow cytometry and immunofluorescence. Human umbilical vein endothelial cells used for the optimization of collagen IV deposition showed a positive correlation with seeding density and a negative one with sub-culture passaging (P < 0.05). Macromolecular crowding significantly increased collagen IV deposition both in human umbilical vein endothelial cells and in patient-derived pericytes (P < 0.01) without affecting proliferation (P > 0.05). Finally, DFU patient-derived pericytes effectively deposited ECM supporting their use for autologous cell sheet production.

Mitochondrial transplantation has emerged as a promising strategy for treating ischemic diseases by restoring mitochondrial function in damaged tissues. This study investigated the therapeutic potential of mitochondria isolated from placenta-derived mesenchymal stem cells (PD-MSCs) in a murine critical limb ischemia (CLI) model. The isolated mitochondria were characterized to confirm their structural integrity, purity, and ATP production capacity before transplantation into an ischemic hindlimb. Results showed that mitochondrial transplantation significantly improved blood flow and muscle regeneration compared with MSC transplantation, as evidenced by laser Doppler perfusion imaging and histological analysis. Enhanced ATP production and increased oxidative phosphorylation complex protein levels were observed, supporting energy metabolism in ischemic conditions. Mitochondrial transplantation also reduced mitochondrial reactive oxygen species (mROS) levels and increased antioxidant enzyme expression, including SOD-2, leading to reduced oxidative stress and apoptosis, as indicated by decreased Bax, cytosolic cytochrome c, and cleaved caspase-3 levels. Furthermore, mitochondrial transplantation promoted angiogenesis and increased vascular density in ischemic muscles by enhancing endothelial cell function. Overall, PD-MSC-derived mitochondrial transplantation demonstrated proved more effective over MSC transplantation in reducing inflammation, restoring mitochondrial function, and supporting tissue recovery, highlighting its promise as an effective therapeutic approach for CLI and other ischemic conditions by directly addressing mitochondrial dysfunction and overcoming the limitations of conventional cell therapies.

This study revealed that adipose-derived mesenchymal stem cell-facilitated ciprofloxacin therapy effectively protected the kidney parenchyma and functional integrity against acute pyelonephritis damage in rodents. In vitro studies revealed that adipose-derived mesenchymal stem cell-derived media significantly suppressed the number of bacterial colony formation units (P < 0.0001). Additionally, the combination of adipose-derived mesenchymal stem cell-ciprofloxacin was superior to either treatment alone on suppressing lipopolysaccharide-induced inflammatory reactions in macrophages and peripheral blood-derived mononuclear cells and attenuated lipopolysaccharide-induced apoptosis/DNA damage in uroepithelial cells (Simian virus Hydrologic Unit Code 1) (all P < 0.0001). Sprague-Dawley rats were categorized into groups 1 (sham-control)/2 (acute pyelonephritis)/3 (acute pyelonephritis-ciprofloxacin)/4 (acute pyelonephritis- adipose-derived mesenchymal stem cell)/5 (acute pyelonephritis-adipose-derived mesenchymal stem cell-ciprofloxacin), and kidneys were harvested by day 5 after acute pyelonephritis induction. The in vivo results revealed that the day-5 mortality rate and creatinine levels at days 2 and 5 were significantly greater in group 2 than in groups 1 and 5 (P = 0.01), whereas the kidney injury score and inflammatory cell infiltration in the kidney were highest in group 2, lowest in group 1, and significantly greater in groups 3 and 4 than in group 5; however, there was no difference between groups 3 and 4 (all P < 0.0001). The upstream inflammatory signaling (toll-like receptor-4, myeloid differentiation primary response 88, tumor necrosis factor receptor associated factor 6 and nuclear factor-kappa B) and downstream inflammatory signaling (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) biomarkers exhibited identical patterns of kidney injury scores among the groups (all P < 0.0001). The results of the present study showed that adipose-derived mesenchymal stem cell-facilitated ciprofloxacin reduced inflammatory signaling-induced kidney parenchymal damage and acute pyelonephritis-induced mortality and preserved kidney function.