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De Sousa, P.A., Perfect, L., Ye, J., Samuels, K., Piotrowska, E., Gordon, M., Mate, R., Abranches, E., Wishart, T.M. 
ORCID: 0000-0002-1973-6654, Dockrell, D.H. and Courtney, A.,
2024.
Hyaluronan in mesenchymal stromal cell lineage differentiation from human pluripotent stem cells: application in serum free culture.
Stem Cell Research and Therapy, 15: 130.
ISSN 1757-6512
Abstract
Background: Hyaluronan (HA) is an extracellular glycosaminoglycan polysaccharide with widespread roles throughout development and in healthy and neoplastic tissues. In pluripotent stem cell culture it can support both stem cell renewal and differentiation. However, responses to HA in culture are influenced by interaction with a range of cognate factors and receptors including components of blood serum supplements, which alter results. These may contribute to variation in cell batch production yield and phenotype as well as heighten the risks of adventitious pathogen transmission in the course of cell processing for therapeutic applications.
Main: Here we characterise differentiation of a human embryo/pluripotent stem cell derived Mesenchymal Stromal Cell (hESC/PSC-MSC)-like cell population by culture on a planar surface coated with HA in serum-free media qualified for cell production for therapy. Resulting cells met minimum criteria of the International Society for Cellular Therapy for identification as MSC by expression of. CD90, CD73, CD105, and lack of expression for CD34, CD45, CD14 and HLA-II. They were positive for other MSC associated markers (i.e.CD166, CD56, CD44, HLA 1-A) whilst negative for others (e.g. CD271, CD71, CD146). In vitro co-culture assessment of MSC associated functionality confirmed support of growth of hematopoietic progenitors and inhibition of mitogen activated proliferation of lymphocytes from umbilical cord and adult peripheral blood mononuclear cells, respectively. Co-culture with immortalized THP-1 monocyte derived macrophages (Mɸ) concurrently stimulated with lipopolysaccharide as a pro-inflammatory stimulus, resulted in a dose dependent increase in pro-inflammatory IL6 but negligible effect on TNFα. To further investigate these functionalities, a bulk cell RNA sequence comparison with adult human bone marrow derived MSC and hESC substantiated a distinctive genetic signature more proximate to the former.
Conclusion: Cultivation of human pluripotent stem cells on a planar substrate of HA in serum-free culture media systems is sufficient to yield a distinctive developmental mesenchymal stromal cell lineage with potential to modify the function of haematopoietic lineages in therapeutic applications.
| Item Type: | Journal article | ||||||
|---|---|---|---|---|---|---|---|
| Publication Title: | Stem Cell Research and Therapy | ||||||
| Creators: | De Sousa, P.A., Perfect, L., Ye, J., Samuels, K., Piotrowska, E., Gordon, M., Mate, R., Abranches, E., Wishart, T.M., Dockrell, D.H. and Courtney, A. | ||||||
| Publisher: | Springer | ||||||
| Date: | 3 May 2024 | ||||||
| Volume: | 15 | ||||||
| ISSN: | 1757-6512 | ||||||
| Identifiers: |
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| Rights: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Jonathan Gallacher | ||||||
| Date Added: | 24 Oct 2024 14:55 | ||||||
| Last Modified: | 24 Oct 2024 14:55 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/52463 |
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