Premium
Scalable Manufacturing of Human Mesenchymal Stromal Cells in the Vertical‐Wheel Bioreactor System: An Experimental and Economic Approach
Author(s) -
Pinto Diogo,
Bandeiras Cátia,
Fuzeta Miguel,
Rodrigues Carlos A. V.,
Jung Sunghoon,
Hashimura Yas,
Tseng RongJeng,
Milligan William,
Lee Brian,
Ferreira Frederico Castelo,
Silva Cláudia,
Cabral Joaquim M. S.
Publication year - 2019
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201800716
Subject(s) - microcarrier , mesenchymal stem cell , bioreactor , stromal cell , biomedical engineering , laboratory flask , cell culture , cell , microbiology and biotechnology , tissue engineering , regenerative medicine , adipose tissue , chemistry , biology , medicine , cancer research , biochemistry , genetics , organic chemistry
Mesenchymal stromal cells (MSC) hold great promise for tissue engineering applications and cell‐based therapies. Large cell doses (>1 × 10 6 cells kg −1 ) and Good Manufacturing Practices (GMP)‐compliant processes are however required for clinical purposes. Here, a serum‐ and xenogeneic‐free (S/XF) microcarrier‐based culture system is established for the expansion of human umbilical cord matrix (UCM)‐ and adipose tissue (AT)‐derived MSC using the Vertical‐Wheel system (PBS‐0.1 MAG; PBS Biotech). UCM and AT MSC are expanded to maximum cell densities of 5.3 ± 0.4 × 10 5 cell mL −1 ( n = 3) and 3.6 ± 0.7 × 10 5 cell mL −1 ( n = 3), respectively, after 7 days of culture, while maintaining their identity, according to standard criteria. An economic evaluation of the process transfer from T‐flasks to PBS‐0.1 MAG shows a reduction in the costs associated with the production of a dose for an average 70 kg adult patient (i.e., 70 million cells). Costs decrease from $17.0 K to $11.1 K for UCM MSC and from $21.5 K to $11.1 K for AT MSC, proving that the transition to Vertical‐Wheel reactors provides a cost‐effective alternative for MSC expansion. The present work reports the establishment of a scalable and cost‐effective culture platform for the manufacturing of UCM and AT MSC in a S/XF microcarrier‐based system.