Technologies for large-scale umbilical cord-derived MSC expansion: Experimental performance and cost of goods analysis

Author(s)

Mizukami, Amanda ^[1] ; Pereira Chilima, Tania D. ^[2] ; Orellana, Maristela D. ^[1] ; Abreu Neto, Mario ^[1] ; Covas, Dimas T. ^[1] ; Farid, Suzanne S. ^[2] ; Swiech, Kamilla ^{[3, 1]}

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Hemotherapy Ctr Ribeirao Preto, BR-14051140 Ribeirao Preto, SP - Brazil

^[2] UCL, Adv Ctr Biochem Engn, Dept Biochem Engn, Gower St, London WC1E 6BT - England

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Biochemical Engineering Journal; v. 135, p. 36-48, JUL 15 2018.
• Web of Science Citations: 10

Abstract

The translation of cell therapies into clinical practice requires a scalable, efficient and cost-effective manufacturing process. This paper presents an integrated experimental and cost analysis of different cell culture technologies for umbilical cord-derived mesenchymal stromal/stem cell expansion: a multi-layer vessel (ML), a stirred tank bioreactor with microcarrriers (STR), a hollow fiber bioreactor (HF) and a packed-bed bioreactor (PB). The results showed that the cell proliferation rate, expansion fold and harvesting efficiency were highest in HF (36.8 +/- 1.7 h; 9.8 +/- 1.0 - fold; 100%). The STR, ML and PB achieved a similar level of cell number with high expansion folds (8.8 +/- 0.39, 8.7 +/- 0.90, 6.9 +/- 1.3 - fold, respectively). However, harvesting efficiency was lowest with PB (18% +/- 0.77), followed by STR (61% +/- 15.7). The cells retained their functional properties post culture in all the technologies evaluated. The experimental results were incorporated into an advanced decisional tool comprising a bioprocess economics model and a stochastic model so as to evaluate the commercial economic feasibility and robustness of different candidate technologies for MSC manufacture. The model predicted that HF would be the least cost-effective option despite its advantageous experimental performance, due to its high consumable and equipment costs. ML ranked first in cost-effectiveness and robustness in this scenario followed by STR. The results also demonstrated how the bioprocess economics model can be used to direct improvements to the culture platforms so as to achieve commercial success according to the reimbursement level. (C) 2018 The Authors. Published by Elsevier B.V. (AU)

• FAPESP's process: 13/23599-5 - Expansion of mesenchymal stromal cells derived from human umbilical cord matrix in bioreactors in serum/xeno-free conditions
• Grantee: Amanda Mizukami Martins
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/23228-4 - In vitro expansion of mesenchymal stromal cells and secretome characterization: therapeutic and biotechnological applications
• Grantee: Amanda Mizukami Martins
• Support Opportunities: Scholarships in Brazil - Doctorate