PMID- 37271923
OWN - NLM
STAT- MEDLINE
DCOM- 20230817
LR  - 20230818
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 10
IP  - 23
DP  - 2023 Aug
TI  - Developing Hypoimmunogenic Human iPSC-Derived Oligodendrocyte Progenitor Cells as 
      an Off-The-Shelf Cell Therapy for Myelin Disorders.
PG  - e2206910
LID - 10.1002/advs.202206910 [doi]
LID - 2206910
AB  - Demyelinating disorders are among the most common and debilitating diseases in 
      neurology. Canavan disease (CD) is a lethal demyelinating disease caused by 
      mutation of the aspartoacylase (ASPA) gene, which leads to the accumulation of 
      its substrate N-acetyl-l-aspartate (NAA), and consequently demyelination and 
      vacuolation in the brain. In this study, hypoimmunogenic human induced 
      pluripotent stem cell (iPSC)-derived oligodendrocyte progenitor cells (OPC) are 
      developed from a healthy donor as an "off-the-shelf" cell therapy. 
      Hypoimmunogenic iPSCs are generated through CRISPR/Cas9 editing of the human 
      leukocyte antigen (HLA) molecules in healthy donor-derived iPSCs and 
      differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) 
      mice and exhibit widespread distribution in the brain. The engrafted OPCs mature 
      into oligodendrocytes that express the endogenous wildtype ASPA gene. 
      Consequently, the transplanted mice exhibit elevated human ASPA expression and 
      enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are 
      able to rescue major pathological features of CD, including defective 
      myelination, extensive vacuolation, and motor function deficits. Moreover, the 
      hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The 
      hypoimmunogenic OPCs can be used as "off-the-shelf" universal donor cells to 
      treat various CD patients and many other demyelinating disorders, especially 
      autoimmune demyelinating diseases, such as multiple sclerosis.
CI  - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Feng, Lizhao
AU  - Feng L
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Chao, Jianfei
AU  - Chao J
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Ye, Peng
AU  - Ye P
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Luong, Qui
AU  - Luong Q
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Sun, Guoqiang
AU  - Sun G
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Cui, Qi
AU  - Cui Q
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Flores, Sergio
AU  - Flores S
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Jackson, Natasha
AU  - Jackson N
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Shayento, Afm Nazmul Hoque
AU  - Shayento ANH
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Sun, Guihua
AU  - Sun G
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Liu, Zhenqing
AU  - Liu Z
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Hu, Weidong
AU  - Hu W
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
AD  - Department of Immunology and Theranostics, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
FAU - Shi, Yanhong
AU  - Shi Y
AUID- ORCID: 0000-0002-3938-5839
AD  - Department of Neurodegenerative Diseases, Beckman Research Institute of City of 
      Hope, 1500 E. Duarte Rd., Duarte, CA, 91010, USA.
LA  - eng
GR  - P30 CA033572/CA/NCI NIH HHS/United States
GR  - U01 NS122101/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20230604
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Myelin Sheath/metabolism/pathology
MH  - *Induced Pluripotent Stem Cells/pathology
MH  - *Oligodendrocyte Precursor Cells/pathology
MH  - Oligodendroglia/metabolism
MH  - *Multiple Sclerosis
MH  - *Canavan Disease/genetics/metabolism/pathology
PMC - PMC10427412
OTO - NOTNLM
OT  - Canavan disease
OT  - allogeneic cell therapy
OT  - demyelinating diseases
OT  - iPSCs
OT  - off-the-shelf cell therapy
OT  - oligodendrocyte progenitor cells (OPC)
OT  - universal donor
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/05 06:42
MHDA- 2023/08/17 06:43
PMCR- 2023/06/04
CRDT- 2023/06/05 00:14
PHST- 2023/04/27 00:00 [revised]
PHST- 2022/11/23 00:00 [received]
PHST- 2023/08/17 06:43 [medline]
PHST- 2023/06/05 06:42 [pubmed]
PHST- 2023/06/05 00:14 [entrez]
PHST- 2023/06/04 00:00 [pmc-release]
AID - ADVS5754 [pii]
AID - 10.1002/advs.202206910 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2023 Aug;10(23):e2206910. doi: 10.1002/advs.202206910. Epub 2023 
      Jun 4.