Knockout of integrin β1 in induced pluripotent stem cells accelerates skin-wound healing by promoting cell migration in extracellular matrix
Abstract Background Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin β1 (Itgb1) is the major integrin subunit that mediat...
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Published in | Stem cell research & therapy Vol. 13; no. 1; pp. 1 - 389 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BioMed Central
30.07.2022
BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Background
Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin β1 (Itgb1) is the major integrin subunit that mediates iPSC-ECM adhesion, suggesting that knocking out
Itgb1
might be an effective method for enhancing the therapeutic efficacy of iPSCs.
Methods
We knocked out
Itgb1
in mouse iPSCs and evaluated its effects on the therapeutic potential of topically applied iPSCs, as well as their underlying in vivo and in vitro mechanisms.
Results
The
Itgb1
-knockout (
Itgb1-
KO) did not change iPSC pluripotency, function, or survival in the absence of embedding in an ECM gel but did accelerate wound healing, angiogenesis, blood perfusion, and survival in skin-wound lesions. However, embedding in an ECM gel inhibited the in vivo effects of wild-type iPSCs but not those of
Itgb1-
knockout iPSCs. Additionally, in vitro results showed that
Itgb1-
knockout decreased iPSC-ECM adhesion while increasing ECM-crossing migration. Moreover, ECM coating on the culture surface did not change cell survival, regardless of
Itgb1
status; however, the in vivo and in vitro functions of both
Itgb1
-knockout and wild-type iPSCs were not affected by the presence of agarose gel, which does not contain integrin-binding sites. Knockout of Integrin α4 (Itga4) did not change the above-mentioned cellular and therapeutic functions of iPSCs.
Conclusions
Itgb1
-knockout increased iPSCs migration and the wound-healing-promoting effect of topically applied iPSCs. These findings suggest the inhibition of Itgb1 expression is a possible strategy for increasing the efficacy of iPSC therapies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1757-6512 1757-6512 |
DOI: | 10.1186/s13287-022-03085-7 |