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

• Published in: Life sciences (1973) Vol. 268; p. 118970
• Main Authors: Buravkova, L.B., Ezdakova, M.I., Andrianova, I.V., Gornostaeva, A.N., Bobyleva, P.I., Andreeva, E.R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-03-2021
• Subjects: Adipose tissue-derived mesenchymal stromal cells (MSCs); Alkaline Phosphatase - metabolism; Bipotential commitment; Chemokines - metabolism; Coculture; Coculture Techniques; Colony-Forming Units Assay; Cord blood hematopoietic stem and progenitor cells (cbHSPCs); Core Binding Factor Alpha 1 Subunit - genetics; Fetal Blood - cytology; Gene Expression Regulation; Hematopoietic Stem Cells - cytology; Humans; Immunophenotyping; Mesenchymal Stem Cells - cytology; Osteoproteins; Stromal Cells - cytology; Adipose tissue-derived mesenchymal stromal cells (MSCs); Coculture; Bipotential commitment; Osteoproteins; Cord blood hematopoietic stem and progenitor cells (cbHSPCs)
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118970

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.
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.
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.
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.