Inter- and intra-donor variability in bone marrow-derived mesenchymal stromal cells

• Verfasst von: Trivedi, Alpa [VerfasserIn]
• Verfasst von: Lin, Maximillian [VerfasserIn]
• Verfasst von: Miyazawa, Byron [VerfasserIn]
• Verfasst von: Nair, Alison [VerfasserIn]
• Verfasst von: Vivona, Lindsay [VerfasserIn]
• Verfasst von: Fang, Xiaohui [VerfasserIn]
• Verfasst von: Bieback, Karen [VerfasserIn]
• Verfasst von: Schäfer, Richard [VerfasserIn]
• Verfasst von: Spohn, Gabriele [VerfasserIn]
• Verfasst von: McKenna, David [VerfasserIn]
• Verfasst von: Zhuo, Hanjing [VerfasserIn]
• Verfasst von: Matthay, Michael A. [VerfasserIn]
• Verfasst von: Pati, Shibani [VerfasserIn]
• Titel: Inter- and intra-donor variability in bone marrow-derived mesenchymal stromal cells
• Titelzusatz: implications for clinical applications
• Verf.angabe: Alpa Trivedi, Maximillian Lin, Byron Miyazawa, Alison Nair, Lindsay Vivona, Xiaohui Fang, Karen Bieback, Richard Schäfer, Gabriele Spohn, David McKenna, Hanjing Zhuo, Michael A. Matthay, Shibani Pati
• E-Jahr: 2024
• Jahr: September 2024
• Umfang: 14 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 30. März 2024, Artikelversion: 21. August 2024 ; Gesehen am 21.10.2024
• Titel Quelle: Enthalten in: Cytotherapy
• Ort Quelle: New York, NY : Elsevier, 1999
• Jahr Quelle: 2024
• Band/Heft Quelle: 26(2024), 9 vom: Sept., Seite 1062-1075
• ISSN Quelle: 1477-2566
• DOI: doi:10.1016/j.jcyt.2024.03.486
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: ARDS
• Sach-SW: bone marrow
• Sach-SW: clinical trials
• Sach-SW: donor variability
• Sach-SW: mesenchymal stromal cells
• K10plus-PPN: 1906328099

Abstract

Background aims - Mesenchymal stromal cells (MSCs) are attractive as a therapeutic modality in multiple disease conditions characterized by inflammation and vascular compromise. Logistically they are advantageous because they can be isolated from adult tissue sources, such as bone marrow (BM). The phase 2a START clinical trial determined BM-MSCs to be safe in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Herein, we examine a subset of the clinical doses of MSCs generated for the phase 2a START trial from three unique donors (1-3), where one of the donors’ donated BM on two separate occasions (donor 3 and 3W). - Methods - The main objective of this study was to correlate properties of the cells from the four lots with plasma biomarkers from treated patients and relevant to ARDS outcomes. To do this we evaluated MSC donor lots for (i) post-thaw viability, (ii) growth kinetics, (iii) metabolism, (iv) surface marker expression, (v) protein expression, (vi) immunomodulatory ability and (vii) their functional effects on regulating endothelial cell permeability. - Results - MSC-specific marker expression and protection of thrombin-challenged endothelial barrier permeability was similar among all four donor lots. Inter and intra-donor variability was observed in all the other in vitro assays. Furthermore, patient plasma ANG-2 and protein C levels at 6 hours post-transfusion were correlated to cell viability in an inter- and intra-donor dependent manner. - Conclusions - These findings highlight the potential of donor dependent (inter-) and collection dependent (intra-) effects in patient biomarker expression.