Abstract
Background aims
Cell therapy for adrenal insufficiency is a potential method for physiological glucocorticoid
and mineralocorticoid replacement. We have previously shown that mouse mesenchymal
stromal cells (MSCs) differentiated into steroidogenic cells by the viral vector–mediated
overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1), an essential
regulator of steroidogenesis, and their implantation extended the survival of bilateral
adrenalectomized (bADX) mice.
Methods
In this study, we examined the capability of NR5A1-induced steroidogenic cells prepared
from human adipose tissue-derived MSCs (MSC [AT]) and the therapeutic effect of the
implantation of human NR5A1-induced steroidogenic cells into immunodeficient bADX
mice.
Results
Human NR5A1-induced steroidogenic cells secreted adrenal and gonadal steroids and
exhibited responsiveness to adrenocorticotropic hormone and angiotensin II in vitro. In vivo, the survival time of bADX mice implanted with NR5A1-induced steroidogenic cells
was significantly prolonged compared with that of bADX mice implanted with control
MSC (AT). Serum cortisol levels, which indicate hormone secretion from the graft,
were detected in bADX mice implanted with steroidogenic cells.
Conclusions
This is the first report to demonstrate steroid replacement by the implantation of
steroid-producing cells derived from human MSC (AT). These results indicate the potential
of human MSC (AT) to be a source of steroid hormone-producing cells.
Key Words
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Article info
Publication history
Published online: May 05, 2023
Accepted:
April 10,
2023
Received:
December 16,
2022
Identification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
