Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells

Ling, L.; Ren, X.; Hassan, A. Binte Mohd; Mah, S.; Smith, R.A.; Tan, C.; van Wijnen, A.; Raghunath, Michael; Nurcombe, V.; Hui, J.; Cool, S.

doi:10.1016/j.jcyt.2019.03.463

Publication type:	Conference poster
Type of review:	Peer review (abstract)
Title:	Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells
Authors:	Ling, L. Ren, X. Hassan, A. Binte Mohd Mah, S. Smith, R.A. Tan, C. van Wijnen, A. Raghunath, Michael Nurcombe, V. Hui, J. Cool, S.
et. al:	No
DOI:	10.1016/j.jcyt.2019.03.463
Proceedings:	Cytotherapy : 25th Annual ISCT Meeting
Volume(Issue):	21
Issue:	5
Page(s):	S71
Conference details:	25th Annual ISCT Meeting, Melbourne, Australia, 1 June – 29 May 2019
Issue Date:	May-2019
Publisher / Ed. Institution:	Elsevier
ISSN:	1465-3249 1477-2566
Language:	English
Subjects:	Mesenchymal stem cell (MSC) therapy; Musculoskeletal regeneration
Subject (DDC):	610.28: Biomedicine, biomedical engineering
Abstract:	Background & Aim: Mesenchymal stem cell (MSC) therapy offers significant potential for musculoskeletal regeneration following trauma or disease. However, the low abundance of MSCs in human bone marrow aspirates necessitates further expansion in culture before their clinical application. Such ex vivo expansion can lead to a loss of stem cell characteristics, and thus unpredictable therapeutic outcomes. This has necessitated moves to develop strategies that lead to retention of MSC potency over serial passages. Studies of the MSC secretome have highlighted the importance of endogenous FGF2 for their survival and maintenance of stemness. In this study, we aimed to establish a glycosaminoglycan-rich culture microenvironment that would bind and activate endogenous FGF2 to increase the growth of multipotent MSCs suitable for therapeutic application. Methods, Results & Conclusion: We show that MSC potency and therapeutic efficacy can be enhanced by sustaining endogenous FGF2 signalling through supplementation with an affinity-selected heparan sulfate co-factor (termed HS8) generated by peptide-based affinity chromatography. Also, HS8 improves the bioavailability of FGF2, so providing MSCs access to active FGF2. This results in a significant increase in the pool of MSCs and sustained growth of multipotent MSCs over extended passaging. Importantly, this increase in cell division does not accelerate telomere loss, or adversely affect colony-forming ability, cell surface marker expression or multipotentiality. When used to treat osteochondral injury to the femoral trochlear groove of NIH nude rats, improvements in ICRS II and O'Driscoll scores were observed, with > 70% of defects treated with MSCs supplemented with HS8 achieving high scores compared with ∼ 50% for control. In a follow-on micropig osteochondral defect study, treatment with MSCs supplemented with HS8 showed significant increases in ICRS II and O'Driscoll scores compared to control. Moreover, Magnetic Resonance Imaging (MRI) analysis demonstrated reduced osteochondral lesioning following treatment with MSCs supplemented with HS8, with Instron biomechanical testing highlighting an associated improvement in biomechanical properties over control. Collectively, these data show that modulation of endogenous FGF2 signals by select heparan glycosaminoglycans represents an effective strategy for the bioprocessing of human mesenchymal stem cells with sustained therapeutic potency.
URI:	https://digitalcollection.zhaw.ch/handle/11475/29875
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Ling, L., Ren, X., Hassan, A. B. M., Mah, S., Smith, R. A., Tan, C., van Wijnen, A., Raghunath, M., Nurcombe, V., Hui, J., & Cool, S. (2019). Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells [Conference poster]. Cytotherapy : 25th Annual ISCT Meeting, 21(5), S71. https://doi.org/10.1016/j.jcyt.2019.03.463

Ling, L. et al. (2019) ‘Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells’, in Cytotherapy : 25th Annual ISCT Meeting. Elsevier, p. S71. Available at: https://doi.org/10.1016/j.jcyt.2019.03.463.

L. Ling et al., “Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells,” in Cytotherapy : 25th Annual ISCT Meeting, May 2019, vol. 21, no. 5, p. S71. doi: 10.1016/j.jcyt.2019.03.463.

LING, L., X. REN, A. Binte Mohd HASSAN, S. MAH, R.A. SMITH, C. TAN, A. VAN WIJNEN, Michael RAGHUNATH, V. NURCOMBE, J. HUI und S. COOL, 2019. Biomimicry of glycosaminoglycans in the bone marrow microenvironment favour the expansion of highly potent human mesenchymal stem cells. In: Cytotherapy : 25th Annual ISCT Meeting. Conference poster. Elsevier. Mai 2019. S. S71

Ling, L., X. Ren, A. Binte Mohd Hassan, S. Mah, R.A. Smith, C. Tan, A. van Wijnen, et al. 2019. “Biomimicry of Glycosaminoglycans in the Bone Marrow Microenvironment Favour the Expansion of Highly Potent Human Mesenchymal Stem Cells.” Conference poster. In Cytotherapy : 25th Annual ISCT Meeting, 21:S71. Elsevier. https://doi.org/10.1016/j.jcyt.2019.03.463.

Ling, L., et al. “Biomimicry of Glycosaminoglycans in the Bone Marrow Microenvironment Favour the Expansion of Highly Potent Human Mesenchymal Stem Cells.” Cytotherapy : 25th Annual ISCT Meeting, vol. 21, no. 5, Elsevier, 2019, p. S71, https://doi.org/10.1016/j.jcyt.2019.03.463.