Hypoxia preconditioned mesenchymal stem cell-derived exosomes induce ex vivo expansion of umbilical cord blood hematopoietic stem cells CD133+ by stimulation of Notch signaling pathway.
Biotechnol Prog
; 38(1): e3222, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34734683
ABSTRACT
Mesenchymal stem cells (MSCs) are crucial cells that play an essential role in the maintenance, self-renewal, and proliferation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow niche. It has been proven that MSCs can be used as a feeder layer for the proliferation of HSCs to enhance the number of HPCs and HSCs. Recently, it has been demonstrated that MSC-derived exosome (MSC-DE) has critical roles in different biological processes in bone marrow (BM). In the current research, we examined the importance of hypoxia-preconditioned MSC-derived exosomes (HP-MSC-DE) and normoxia-preconditioned MSC-derived exosomes (NP-MSC-DE) in the self-renewal and long-term clonogenic potential of umbilical cord blood hematopoietic stem cells (UCB-HSCs). We showed that the secretion rate and component of the exosome (EXO) were changed in HP-MSC-DE compared to NP-MSC-DE. Notably, the Jagged-1 (Notch ligand) content of EXO was much more plentiful in HP-MSC-DE compared to NP-MSC-DE. The addition of HP-MSC-DE enriched by Jagged-1 to the co-culture system stimulates the Notch pathway on the membrane of UCB-HSCs CD133+ and enhances proliferation. HP-MSC-DE induction using an anti-Jagged-1 antibody suppresses all biological functions of the Jagged-1 protein. Importantly, HP-MSC-DE containing Jagged-1 could change the biology of HSCs CD133+ and increase the self-renewal capacity, quiescence, and clonogenic potential of CD133+ cells. Moreover, they support generating a large number of primitive cells. Our study signified the importance of HP-MSC-DE in the proliferation of UCB-HSCs CD133+, which manifested therapeutic applications of EXO in the enhanced number of HSCs and subsequently alleviated bone marrow transplantation.
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MEDLINE
Assunto principal:
Exossomos
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Células-Tronco Mesenquimais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article