PMID- 35877325
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220729
IS  - 2306-5354 (Print)
IS  - 2306-5354 (Electronic)
IS  - 2306-5354 (Linking)
VI  - 9
IP  - 7
DP  - 2022 Jun 23
TI  - Large-Scale Expansion of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a 
      Stirred Suspension Bioreactor Enabled by Computational Fluid Dynamics Modeling.
LID - 10.3390/bioengineering9070274 [doi]
LID - 274
AB  - Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) hold great 
      potential to generate novel and curative cell therapy products. However, the 
      current large-scale cultivation of hUCMSCs is based on empirical 
      geometry-dependent methods, limiting the generation of high-quantity and 
      high-quality hUCMSCs for clinical therapy. Herein, we develop a novel scale-up 
      strategy based on computational fluid dynamics (CFD) to effectively expand the 
      hUCMSCs in a 3D tank bioreactor. Using a standardized hUCMSCs line on 
      microcarriers, we successfully translated and expanded the hUCMSCs from a 200 mL 
      spinner flask to a 1.5 L computer-controlled bioreactor by matching the shear 
      environment and suspending the microcarrier. Experimental results revealed that 
      the batch-cultured hUCMSCs in bioreactors with an agitation speed of 40 rpm 
      shared a more favorable growth and physiological state, similar to that run at 45 
      rpm in a 200 mL spinner flask, showing comparability in both culture systems. 
      Notably, the maximum cell density reached up to 27.3 x 10(5) cells/mL in 
      fed-batch culture, 2.9 folds of that of batch culture and 20.2 times of seeding 
      cells. As such, efficient process optimization and scale-up expansion of hUCMSCs 
      were achieved in the microcarrier-based bioreactor system by the developed CFD 
      simulation strategy, which provided an alternative toolbox to generate massive 
      and standardized curative cell therapy products.
FAU - Zhang, Junhong
AU  - Zhang J
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., Shanghai 200237, China.
FAU - Peng, Yan
AU  - Peng Y
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., Shanghai 200237, China.
FAU - Guo, Meijin
AU  - Guo M
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., Shanghai 200237, China.
FAU - Li, Chao
AU  - Li C
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., Shanghai 200237, China.
LA  - eng
PT  - Journal Article
DEP - 20220623
PL  - Switzerland
TA  - Bioengineering (Basel)
JT  - Bioengineering (Basel, Switzerland)
JID - 101676056
PMC - PMC9312327
OTO - NOTNLM
OT  - UC-mesenchymal stem cells
OT  - computational fluid dynamics
OT  - microcarrier-based bioreactors
OT  - scale-up expansion
OT  - three-dimensional suspension culture
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/26 06:00
MHDA- 2022/07/26 06:01
PMCR- 2022/06/23
CRDT- 2022/07/25 12:43
PHST- 2022/05/14 00:00 [received]
PHST- 2022/06/15 00:00 [revised]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/07/25 12:43 [entrez]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/07/26 06:01 [medline]
PHST- 2022/06/23 00:00 [pmc-release]
AID - bioengineering9070274 [pii]
AID - bioengineering-09-00274 [pii]
AID - 10.3390/bioengineering9070274 [doi]
PST - epublish
SO  - Bioengineering (Basel). 2022 Jun 23;9(7):274. doi: 10.3390/bioengineering9070274.