PMID- 33463310
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20230617
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
VI  - 6
IP  - 7
DP  - 2020 Jul 13
TI  - Decellularized Tissue Matrix Enhances Self-Assembly of Islet Organoids from 
      Pluripotent Stem Cell Differentiation.
PG  - 4155-4165
LID - 10.1021/acsbiomaterials.0c00088 [doi]
AB  - Regenerating human islet organoids from stem cells remains a significant 
      challenge because of our limited knowledge on cues essential for developing the 
      endocrine organoids in vitro. In this study, we discovered that a natural 
      material prepared from a decellularized rat pancreatic extracellular matrix 
      (dpECM) induces the self-assembly of human islet organoids during induced 
      pluripotent stem cell (iPSC) pancreatic differentiation. For the first time, we 
      demonstrated that the iPSC-derived islet organoids formed in the presence of the 
      dpECM are capable of glucose-responsive secretion of both insulin and glucagon, 
      two major hormones that maintain blood glucose homeostasis. The characterization 
      of the organoids revealed that the organoids consisted of all major endocrine 
      cell types, including alpha, beta, delta, and pancreatic polypeptide cells, that were 
      assembled into a tissue architecture similar to that of human islets. The 
      exposure of iPSCs to the dpECM during differentiation resulted in considerably 
      elevated expression of key pancreatic transcription factors such as PDX-1, MAFA, 
      and NKX6.1 and the production of all major hormones, including insulin, glucagon, 
      somatostatin, and pancreatic polypeptide from stem cell-derived organoids. This 
      study highlights the importance of natural, bioactive biomaterials for building 
      microenvironments crucial to regenerating islet organoids from stem cells.
FAU - Bi, Huanjing
AU  - Bi H
AD  - Department of Biomedical Engineering, Binghamton University, State University of 
      New York (SUNY), Binghamton, New York 13902, United States.
FAU - Karanth, Soujanya S
AU  - Karanth SS
AD  - Department of Biomedical Engineering, Binghamton University, State University of 
      New York (SUNY), Binghamton, New York 13902, United States.
FAU - Ye, Kaiming
AU  - Ye K
AUID- ORCID: 0000-0001-7736-9875
AD  - Department of Biomedical Engineering, Binghamton University, State University of 
      New York (SUNY), Binghamton, New York 13902, United States.
AD  - Center of Biomanufacturing for Regenerative Medicine, Binghamton University, 
      State University of New York (SUNY), Binghamton, New York 13902, United States.
FAU - Stein, Roland
AU  - Stein R
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University, 
      Nashville, Tennessee 37232, United States.
FAU - Jin, Sha
AU  - Jin S
AUID- ORCID: 0000-0002-8033-8110
AD  - Department of Biomedical Engineering, Binghamton University, State University of 
      New York (SUNY), Binghamton, New York 13902, United States.
AD  - Center of Biomanufacturing for Regenerative Medicine, Binghamton University, 
      State University of New York (SUNY), Binghamton, New York 13902, United States.
LA  - eng
GR  - R15 EB027391/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200611
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
RN  - 0 (Insulin)
SB  - IM
MH  - Cell Differentiation
MH  - Insulin
MH  - *Islets of Langerhans
MH  - Organoids
MH  - *Pluripotent Stem Cells
OTO - NOTNLM
OT  - detergent-free decellularization
OT  - glucagon
OT  - human induced pluripotent stem cells
OT  - insulin
OT  - islet organoids
OT  - pancreatic extracellular matrix
EDAT- 2021/01/20 06:00
MHDA- 2021/05/15 06:00
CRDT- 2021/01/19 08:40
PHST- 2021/01/19 08:40 [entrez]
PHST- 2021/01/20 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
AID - 10.1021/acsbiomaterials.0c00088 [doi]
PST - ppublish
SO  - ACS Biomater Sci Eng. 2020 Jul 13;6(7):4155-4165. doi: 
      10.1021/acsbiomaterials.0c00088. Epub 2020 Jun 11.