PMID- 32046184
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 8
IP  - 2
DP  - 2020 Feb 7
TI  - A Versatile Model of Microfluidic Perifusion System for the Evaluation of 
      C-Peptide Secretion Profiles: Comparison Between Human Pancreatic Islets and 
      HLSC-Derived Islet-Like Structures.
LID - 10.3390/biomedicines8020026 [doi]
LID - 26
AB  - A robust and easy-to-use tool for the ex vivo dynamic evaluation of pancreatic 
      islet (PI) function is essential for further development of novel cell-based 
      therapeutic approaches to treating diabetes. Here, we developed four different 
      glucose perifusion protocols (GPPs) in a microfluidic perifusion system (MPS), 
      based entirely on commercially available components. After validation, the GPPs 
      were used to evaluate C-peptide secretion profiles of PIs derived from different 
      donors (healthy, obese, and type 2 diabetic) and from human liver 
      stem-cell-derived islet-like structures (HLSC-ILS). Using this device, we 
      demonstrated that PIs derived from healthy donors displayed a physiological 
      C-peptide secretion profile as characterized by the response to (a) different 
      glucose concentrations, (b) consecutive pulses of high-glucose concentrations, 
      (c) a glucose threshold ranging from 5-8 mM, and (d) a constant high-glucose 
      perifusion in a biphasic manner. Moreover, we were able to detect a dysregulated 
      secretion profile in PIs derived from both obese and type 2 diabetes mellitus 
      (T2DM) donors. Finally, we also evaluated the kinetic secretion profiles of 
      HLSC-ILS, demonstrating that, nonetheless, with a lower amplitude of secretion 
      compared to PI derived from healthy donors, they were already glucose-responsive 
      on day seven post-differentiation. In conclusion, we have provided evidence that 
      our MPS is a versatile device and may represent a valuable tool to study 
      insulin-producing cells in vitro.
FAU - Gomez, Yonathan
AU  - Gomez Y
AD  - Unicyte AG, Molecular Biotechnology Center (MBC), University of Turin. Via Nizza, 
      52, 10126 Turin, Italy.
FAU - Navarro-Tableros, Victor
AU  - Navarro-Tableros V
AD  - i3T Societa per la Gestione Dell'incubatore di Imprese e per il Trasferimento 
      Tecnologico Scarl, University of Turin, 10126 Turin, Italy.
FAU - Tetta, Ciro
AU  - Tetta C
AD  - Unicyte AG, Unicyte srl, Via Lugaro, 15, 10100 Turin, Italy.
FAU - Camussi, Giovanni
AU  - Camussi G
AD  - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 
      Turin, Italy.
FAU - Brizzi, Maria Felice
AU  - Brizzi MF
AD  - Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 
      Turin, Italy.
LA  - eng
GR  - Reg2019/Unicyte (Oberdorf NW, Switzerland)/
PT  - Journal Article
DEP - 20200207
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC7168272
OTO - NOTNLM
OT  - C-peptide
OT  - HLSC-ILS
OT  - T2DM
OT  - human pancreatic islets
OT  - microfluidic
OT  - obese
OT  - perifusion
COIS- Y.G. and C.T are employed by a commercial company (Unicyte AG) and contributed to 
      the study as researcher. Y.G., V.N.-T., C.T., and G.C are named inventors in 
      related patents. G.C. is a component of the scientific advisory board of Unicyte 
      AG. The funders had no role in the design of the study; in the collection, 
      analyses, or interpretation of data; in the writing of the manuscript, or in the 
      decision to publish the results.
EDAT- 2020/02/13 06:00
MHDA- 2020/02/13 06:01
PMCR- 2020/02/07
CRDT- 2020/02/13 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/02/05 00:00 [accepted]
PHST- 2020/02/13 06:00 [entrez]
PHST- 2020/02/13 06:00 [pubmed]
PHST- 2020/02/13 06:01 [medline]
PHST- 2020/02/07 00:00 [pmc-release]
AID - biomedicines8020026 [pii]
AID - biomedicines-08-00026 [pii]
AID - 10.3390/biomedicines8020026 [doi]
PST - epublish
SO  - Biomedicines. 2020 Feb 7;8(2):26. doi: 10.3390/biomedicines8020026.