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Background: Increasing evidence suggests the safety and efficacy of mesenchymal stromal cells (MSC) as advanced therapy medicinal products because of their immunomodulatory properties and supportive role in hematopoiesis. Although bone marrow remains the most common source for obtaining off-the-shelf MSC, cord blood (CB) represents an alternative source, which can be collected noninvasively and without major ethical concerns. However, the low estimated frequency and inconsistency of successful isolation represent open challenges for the use of CB-derived MSC in clinical trials. This study explores whether CB may represent a suitable source of MSC for clinical use and analyzes several in vitro parameters useful to better define the quality of CB-derived MSC prior to clinical application.
Methods: CB units (n = 50) selected according to quality criteria (CB volume ≥ 20 ml, time from collection ≤ 24 h) were cultured using a standardized procedure for CB-MSC generation. MSC were analyzed for their growth potential and secondary colony-forming capacity. Immunophenotype and multilineage differentiation potential of culture-expanded CB-MSC were assessed to verify MSC identity. The immunomodulatory activity at resting conditions and after inflammatory priming (IFN-γ-1b and TNF-α for 48 hours) was explored to assess the in vitro potency of CB-MSC prior to clinical application. Molecular karyotyping was used to assess the genetic stability after prolonged MSC expansion.
Results: We were able to isolate MSC colonies from 44% of the processed units. Our results do not support a role of CB volume in determining the outcome of the cultures, in terms of both isolation and proliferative capacity of CB-MSC. Particularly, we have confirmed the existence of two different CB-MSC populations named short- and long-living (SL- and LL-) CBMSC, clearly diverging in their growth capacity and secondary colony-forming efficiency. Only LL-CBMSC were able to expand consistently and to survive for longer periods in vitro, while preserving genetic stability. Therefore, they may represent interesting candidates for therapeutic applications. We have also observed that LL-CBMSC were not equally immunosuppressive, particularly after inflammatory priming and despite upregulating priming-inducible markers.
Conclusions: This work supports the use of CB as a potential MSC source for clinical applications, remaining more readily available compared to conventional sources. We have provided evidence that not all LL-CBMSC are equally immunosuppressive in an inflammatory environment, suggesting the need to include the assessment of potency among the release criteria for each CB-MSC batch intended for clinical use, at least for the treatment of immune disorders as GvHD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260040 | PMC |
http://dx.doi.org/10.1186/s13287-016-0465-2 | DOI Listing |
Am J Clin Pathol
December 2024
Department of Pathology and Laboratory Medicine, Cleveland Clinic Foundation, Cleveland, OH, United States.
Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.
Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.
Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).
Clin Transl Oncol
December 2024
Department of Medical Oncology, Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Purpose: The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain.
Methods: This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined.
Dermatol Ther (Heidelb)
December 2024
Department of Cell Biology and Physiology, The Neuroscience Center, College of Life Sciences, Brigham Young University, Provo, UT, 84602, USA.
Introduction: Retinol has a long history of treating skin conditions, including photoaging. However, skin irritation with repeated use of retinol is well documented. The present study assessed the effectiveness of a novel topical formulation, referred to as retinol topical formulation (RTF), to improve the quality of skin health.
View Article and Find Full Text PDFKnee Surg Sports Traumatol Arthrosc
December 2024
Sporthopaedicum, Berlin, Germany.
Purpose: Sulcus-deepening trochleoplasty (TP) effectively treats patellofemoral (PF) instability (PFI) caused by high-grade trochlear dysplasia (TD), but current evidence is based on small case series. We hypothesised, that TP would result in significant functional improvements and a low re-dislocation rate but would not accelerate the progression of PF cartilage deterioration.
Methods: We retrospectively reviewed all TP cases performed by a single surgeon between 2015 and 2021.
Mol Genet Metab Rep
December 2024
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Introduction: For patients with acute intermittent porphyria (AIP), a true attack could be difficult to distinguish from chronic abdominal pain. This study focused on treatment responses from two patients with confirmed elevated biochemical data (delta-aminolevulinic acid (ALA), porphobilinogen (PBG)) and clinical evidence for acute attacks before starting givosiran.
Methods: Data from patients who participated in the phase III givosiran trial in Taiwan between May 2018 and May 2021 were reviewed.
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