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
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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