PMID- 37511568
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20230731
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 14
DP  - 2023 Jul 22
TI  - Hypoimmunogenic Human Pluripotent Stem Cells as a Powerful Tool for Liver 
      Regenerative Medicine.
LID - 10.3390/ijms241411810 [doi]
LID - 11810
AB  - Induced pluripotent stem cells (iPSC) have huge potential as cell therapy for 
      various diseases, given their potential for unlimited self-renewal and capability 
      to differentiate into a wide range of cell types. Although autologous iPSCs 
      represents the ideal source for patient-tailored regenerative medicine, the high 
      costs of the extensive and time-consuming production process and the 
      impracticability for treating acute conditions hinder their use for broad 
      applications. An allogeneic iPSC-based strategy may overcome these issues, but it 
      carries the risk of triggering an immune response. So far, several approaches 
      based on genome-editing techniques to silence human leukocyte antigen class I 
      (HLA-I) or II (HLA-II) expression have been explored to overcome the immune 
      rejection of allogeneic iPSCs. In this study, we employed the CRISPR/Cas9 
      (clustered regularly interspaced short palindromic repeats/CRISPR associated 
      protein 9) system to delete the beta2-Microglobulin (B2M) and the Class II Major 
      Histocompatibility Complex Transactivator (CIITA) genes, essential for the 
      correct surface expression of HLA-I and HLA-II proteins. The resulting 
      hypoimmunogenic iPSC line has a normal karyotype, expresses the pluripotency stem 
      cell markers, and is capable of differentiating into the three embryonic germ 
      layers. Furthermore, we showed that it specifically retains the ability to 
      differentiate towards different liver cells, such as endothelial-like cells, 
      hepatocyte-like cells, and hepatic stellate-like cells. Our results indicate that 
      hypoimmunogenic iPSCs could give a new cost-effective and off-the-shelf 
      opportunity for cell therapy in liver diseases.
FAU - Trionfini, Piera
AU  - Trionfini P
AUID- ORCID: 0000-0002-6599-0709
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Romano, Elena
AU  - Romano E
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Varinelli, Marco
AU  - Varinelli M
AUID- ORCID: 0000-0001-9046-9555
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Longaretti, Lorena
AU  - Longaretti L
AUID- ORCID: 0000-0002-4366-4152
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Rizzo, Paola
AU  - Rizzo P
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Giampietro, Roberta
AU  - Giampietro R
AUID- ORCID: 0000-0002-2349-5224
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Caroli, Annalina
AU  - Caroli A
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Aiello, Sistiana
AU  - Aiello S
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Todeschini, Marta
AU  - Todeschini M
AUID- ORCID: 0000-0003-3422-8815
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Casiraghi, Federica
AU  - Casiraghi F
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Remuzzi, Giuseppe
AU  - Remuzzi G
AUID- ORCID: 0000-0002-6194-3446
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Benigni, Ariela
AU  - Benigni A
AUID- ORCID: 0000-0002-4721-5485
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
FAU - Tomasoni, Susanna
AU  - Tomasoni S
AUID- ORCID: 0000-0002-7212-2512
AD  - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.
LA  - eng
GR  - GGP20073/Telethon Foundation/
GR  - NA/Roche (Italy)/
PT  - Journal Article
DEP - 20230722
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Humans
MH  - Regenerative Medicine
MH  - *Pluripotent Stem Cells
MH  - Gene Editing/methods
MH  - *Induced Pluripotent Stem Cells
MH  - Histocompatibility Antigens Class I/genetics/metabolism
MH  - Liver
PMC - PMC10380710
OTO - NOTNLM
OT  - cell therapy
OT  - endothelial cells
OT  - hepatic stellate cells
OT  - hepatocytes
OT  - hypoimmunogenic iPSC
OT  - regenerative medicine
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:50
MHDA- 2023/07/31 06:43
PMCR- 2023/07/22
CRDT- 2023/07/29 01:25
PHST- 2023/06/07 00:00 [received]
PHST- 2023/07/13 00:00 [revised]
PHST- 2023/07/19 00:00 [accepted]
PHST- 2023/07/31 06:43 [medline]
PHST- 2023/07/29 11:50 [pubmed]
PHST- 2023/07/29 01:25 [entrez]
PHST- 2023/07/22 00:00 [pmc-release]
AID - ijms241411810 [pii]
AID - ijms-24-11810 [pii]
AID - 10.3390/ijms241411810 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jul 22;24(14):11810. doi: 10.3390/ijms241411810.