Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing: Considerations for Manufacture of Cell Therapies

Giulia Detela, Owen W Bain, Hae-Won Kim, David J Williams, Chris Mason, Anthony Mathur, Ivan B Wall

Research output: Contribution to journalArticle

Abstract

Human mesenchymal stromal cells (hMSCs) are excellent candidates for cell therapy but their expansion to desired clinical quantities can be compromised by ex vivo processing, due to differences between donor material and process variation. The aim of this article is to characterize growth kinetics of healthy baseline "reference" hMSCs using typical manual processing. Bone-marrow derived hMSCs from ten donors are isolated based on plastic adherence, expanded, and analyzed for their growth kinetics until passage 4. Results indicate that hMSC density decreases with overall time in culture (p < 0.001) but no significant differences are observed between successive passages after passage 1. In addition, fold increase in cell number dropped between passage 1 and 2 for three batches, which correlated to lower performance in total fold increase and expansion potential of these batches, suggesting that proliferative ability of hMSCs can be predicted at an early stage. An indicative bounded operating window is determined between passage 1 and 3 (PDL < 10), despite the high inter-donor variability present under standardized hMSC expansion conditions used. hMSC growth profile analysis will be of benefit to cell therapy manufacturing as a tool to predict culture performance and attainment of clinically-relevant yields, therefore stratifying the patient population based on early observation.

Original languageEnglish
Article number1700085
JournalBiotechnology Journal
Volume13
Issue number2
Early online date25 Jan 2018
DOIs
Publication statusPublished - 2 Feb 2018

Bibliographical note

© 2018 The Authors. Biotechnology Journal Published by WILEY-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding: Priority Research Centers Program, National Research Foundation of Korea, Ministry of Education, Science, and Technology (grant no. 2009-0093829); Engineering and Physical Science Research Council Industrial Doctoral Training Centre in Bioprocess Engineering Leadership (EP/G034656/1) and the UK Stem Cell Foundation.

Keywords

  • Adipogenesis
  • Adolescent
  • Bone Marrow Cells/cytology
  • Cell Adhesion
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy
  • Cells, Cultured
  • Chondrogenesis
  • Culture Media/chemistry
  • Humans
  • Male
  • Mesenchymal Stem Cells/cytology
  • Osteogenesis
  • Tissue Donors

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