Bone marrow donor selection and characterization of MSCs is critical for pre-clinical and clinical cell dose production
Autor: | Kristen Valanoski, Alpa Trivedi, Sawyer Smith, Stuart L. Gibb, Lindsay R. Vivona, Daniel R. Potter, James Murphy, Martin A. Schreiber, Shibani Pati, Philip J. Norris, Maximillian Lin, Byron Miyazawa, Mars Stone |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Swine medicine.medical_treatment Cell Culture Techniques lcsh:Medicine Regenerative Medicine Medical and Health Sciences 0302 clinical medicine Conditioned Stem Cell Research - Nonembryonic - Human Electric Impedance Stem cell therapy medicine.diagnostic_test Cell Differentiation Hematology General Medicine Stem-cell therapy Endothelial stem cell medicine.anatomical_structure Viability 030220 oncology & carcinogenesis Differentiation Stem Cell Research - Nonembryonic - Non-Human Female Development of treatments and therapeutic interventions Immunology Bone Marrow Cells Biology Mesenchymal Stem Cell Transplantation General Biochemistry Genetics and Molecular Biology Donor Selection Immunophenotyping Flow cytometry 03 medical and health sciences Clinical Research Donor variability medicine Animals Humans Cell Lineage Cell Shape Cell Proliferation Transplantation 5.2 Cellular and gene therapies Cluster of differentiation Donor selection Bioprocessing Research Mesenchymal stem cell lcsh:R Endothelial Cells Mesenchymal Stem Cells Stem Cell Research Culture Media 030104 developmental biology Cell culture Culture Media Conditioned Cancer research Bone marrow Biomarkers |
Zdroj: | Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-16 (2019) Journal of Translational Medicine Journal of translational medicine, vol 17, iss 1 |
ISSN: | 1479-5876 |
Popis: | Background Cell based therapies, such as bone marrow derived mesenchymal stem cells (BM-MSCs; also known as mesenchymal stromal cells), are currently under investigation for a number of disease applications. The current challenge facing the field is maintaining the consistency and quality of cells especially for cell dose production for pre-clinical testing and clinical trials. Here we determine how BM-donor variability and thus the derived MSCs factor into selection of the optimal primary cell lineage for cell production and testing in a pre-clinical swine model of trauma induced acute respiratory distress syndrome. Methods We harvested bone marrow and generated three different primary BM-MSCs from Yorkshire swine. Cells from these three donors were characterized based on (a) phenotype (morphology, differentiation capacity and flow cytometry), (b) in vitro growth kinetics and metabolic activity, and (c) functional analysis based on inhibition of lung endothelial cell permeability. Results Cells from each swine donor exhibited varied morphology, growth rate, and doubling times. All expressed the same magnitude of standard MSC cell surface markers by flow cytometry and had similar differentiation potential. Metabolic activity and growth potential at each of the passages varied between the three primary cell cultures. More importantly, the functional potency of the MSCs on inhibition of endothelial permeability was also cell donor dependent. Conclusion This study suggests that for production of MSCs for cell-based therapy, it is imperative to examine donor variability and characterize derived MSCs for marker expression, growth and differentiation characteristics and testing potency in application dependent assays prior to selection of the optimal cell lineage for large scale expansion and dose production. Electronic supplementary material The online version of this article (10.1186/s12967-019-1877-4) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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