Сord blood hematopoietic stem cells ex vivo enhance the bipotential commitment of adipose mesenchymal stromal progenitors.

Autor: Buravkova LB; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia; Faculty of Fundamental Medicine, Moscow State University, Moscow, Russia., Ezdakova MI; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Andrianova IV; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Gornostaeva AN; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia., Bobyleva PI; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia; Faculty of Fundamental Medicine, Moscow State University, Moscow, Russia. Electronic address: blastoblast@gmail.com., Andreeva ER; Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Mar 01; Vol. 268, pp. 118970. Date of Electronic Publication: 2020 Dec 29.
DOI: 10.1016/j.lfs.2020.118970
Abstrakt: Aims: Stroma-dependent ex vivo expansion of hematopoietic stem progenitor cells (HSPCs) is a valid approach for cell therapy needs. Our goal was to verify whether HSPCs can affect stromal cells to optimize their functions during ex vivo expansion.
Main Methods: HSPCs from cord blood (cb) were cocultured with growth-arrested adipose mesenchymal stromal cells (MSCs). Commitment-related transcriptional and secretory profiles as well as hematopoiesis-supportive activity of intact and osteo-induced MSCs were examined.
Key Findings: During expansion, cbHSPCs affected the functional state of MSCs, contributing to the formation of early stromal progenitors with a bipotential osteo-adipogenic profile. This was evidenced by the upregulation of certain MSC genes of osteo- and adipodifferentiation (ALPL, RUNX2, BGLAP, CEBPA, ADIPOQ), as well as by elevated alkaline phosphatase activity and altered osteoprotein patterns. Joint paracrine profiles upon coculture were characterized by a balance of "positive" (GM-SCF) and "negative" (IP-10, MIP-1α, MCP-3) myeloid regulators, effectively supporting expansion of both committed and primitive cbHSPCs. Short-term (72 h) osteoinduction prior to coculture resulted in more pronounced shift of the bipotential transcriptomic and osteoprotein profiles. The increased proportions of late primitive CD133 - /CD34 + cbHSPCs and unipotent CFUs suggested that cbHSPCs after expansion on osteo-MSCs were more committed versus cbHSPCs from coculture with non-differentiated MSCs.
Significance: During ex vivo expansion, cbHSPCs can drive the bipotential osteo-adipogenic commitment of MSCs, providing a specific hematopoiesis-supportive milieu. Short-term preliminary osteo-induction enhanced the development of the bipotential profile, leading to more pronounced functional polarization of cbHSPCs, which may be of interest in an applied context.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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