PMID- 35733700
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230602
IS  - 0920-9069 (Print)
IS  - 1573-0778 (Electronic)
IS  - 0920-9069 (Linking)
VI  - 74
IP  - 3
DP  - 2022 Jun
TI  - Development of a novel feeding regime for large scale production of human 
      umbilical cord mesenchymal stem/stromal cells.
PG  - 351-369
LID - 10.1007/s10616-022-00523-5 [doi]
AB  - Human umbilical cord mesenchymal stem/stromal cells (hUC-MSCs) have attracted 
      significant research interests in regenerative medicine and cell-based therapies 
      due to their minimally invasive isolation procedure, abundant availability, 
      allogenic nature, improved proliferation capacity and tri-lineage differentiation 
      potential. However, the challenge in harvesting a sufficient number of hUC-MSCs 
      through conventional static culture for downstream application hinders the 
      downstream clinical translation of hUC-MSCs. Hence, an alternative culture method 
      that can facilitate large-scale expansion is highly desirable. Herein, we 
      developed a microcarrier-based dynamic culture system to culture hUC-MSCs 
      combined fed-batch mode with medium refreshment to decrease concentrations of 
      metabolic wastes, improve nutrient supplement and reduce the amount of medium 
      used for cell culture. Instead of refreshing medium based on the pre-determined 
      frequency, the replacement and feeding of medium using the novel feeding regime 
      were carried out based on consumption of nutrients (glucose and glutamine) and 
      production of metabolic waste (lactate and ammonia) to maintain a balanced and 
      benign culture microenvironment. The optimal process allowed over 20 folds 
      increase of cell with a maximum cell density at (24.13 +/- 0.59) x 10(5) cells/mL. 
      In addition, no significant alteration of cell surface markers of hUC-MSCs 
      derived from dynamic conditions was observed compared to static conditions. 
      Impressively, over 99.8% of the cellular population showed the desired positive 
      expression of CD73, CD90 and CD105, while less than 0.2% of the population showed 
      undesired negative expression of CD34, CD45 and HLA-DR. More importantly, 
      hUC-MSCs derived from our dynamic culture condition still maintained their 
      trilineage differentiation capacity. SUPPLEMENTARY INFORMATION: The online 
      version contains supplementary material available at 10.1007/s10616-022-00523-5.
CI  - (c) The Author(s), under exclusive licence to Springer Nature B.V. 2022.
FAU - Dai, Yichen
AU  - Dai Y
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., P.O. box 329#, Shanghai, 200237 China. GRID: 
      grid.28056.39. ISNI: 0000 0001 2163 4895
FAU - Cui, Xiaolin
AU  - Cui X
AD  - Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, 
      Department of Orthopaedic Surgery & Musculoskeletal Medicine, University of 
      Otago, Christchurch, 8011 New Zealand. GRID: grid.29980.3a. ISNI: 0000 0004 1936 
      7830
FAU - Zhang, Ge
AU  - Zhang G
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., P.O. box 329#, Shanghai, 200237 China. GRID: 
      grid.28056.39. ISNI: 0000 0001 2163 4895
AD  - State Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem 
      Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, 200127 China. GRID: grid.16821.3c. ISNI: 0000 0004 0368 8293
FAU - Mohsin, Ali
AU  - Mohsin A
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., P.O. box 329#, Shanghai, 200237 China. GRID: 
      grid.28056.39. ISNI: 0000 0001 2163 4895
FAU - Xu, Huiming
AU  - Xu H
AUID- ORCID: 0000-0003-4823-6920
AD  - State Key Laboratory of Oncogenes and Related Genes, and Renji-MedX Clinical Stem 
      Cell Research Center RenJi Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, 200127 China. GRID: grid.16821.3c. ISNI: 0000 0004 0368 8293
FAU - Zhuang, Yingping
AU  - Zhuang Y
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., P.O. box 329#, Shanghai, 200237 China. GRID: 
      grid.28056.39. ISNI: 0000 0001 2163 4895
FAU - Guo, Meijin
AU  - Guo M
AUID- ORCID: 0000-0002-3171-4802
AD  - State Key Laboratory of Bioreactor Engineering, East China University of Science 
      and Technology, 130 Meilong Rd., P.O. box 329#, Shanghai, 200237 China. GRID: 
      grid.28056.39. ISNI: 0000 0001 2163 4895
LA  - eng
PT  - Journal Article
DEP - 20220310
PL  - United States
TA  - Cytotechnology
JT  - Cytotechnology
JID - 8807027
PMC - PMC9207013
OTO - NOTNLM
OT  - Dynamic culture
OT  - Fed-batch
OT  - Medium refreshment
OT  - Mesenchymal stem/stromal cells
OT  - Microcarrier
COIS- Conflict of interestThe authors declare that they have no conflicts to declare.
EDAT- 2022/06/24 06:00
MHDA- 2022/06/24 06:01
PMCR- 2023/06/01
CRDT- 2022/06/23 02:27
PHST- 2021/06/23 00:00 [received]
PHST- 2022/01/23 00:00 [accepted]
PHST- 2022/06/23 02:27 [entrez]
PHST- 2022/06/24 06:00 [pubmed]
PHST- 2022/06/24 06:01 [medline]
PHST- 2023/06/01 00:00 [pmc-release]
AID - 523 [pii]
AID - 10.1007/s10616-022-00523-5 [doi]
PST - ppublish
SO  - Cytotechnology. 2022 Jun;74(3):351-369. doi: 10.1007/s10616-022-00523-5. Epub 
      2022 Mar 10.