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Article ; Online: Bone formation by human paediatric marrow stromal cells in a functional allogeneic immune system.

Palomares Cabeza, Virginia / Fahy, Niamh / Kiernan, Caoimhe H / Lolli, Andrea / Witte-Bouma, Janneke / Fahmy Garcia, Shorouk / Merino, Ana / Kops, Nicole / Ridwan, Yanto / Wolvius, Eppo B / Brama, Pieter A J / Hoogduijn, Martin J / Farrell, Eric

Biomaterials

2024 Volume 306, Page(s) 122471

Abstract: Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in ... ...

Abstract	Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in immunodeficient pre-clinical models. However, an insight into the interactions between the allogeneic immune system and the human MSC-derived bone grafts has not been fully achieved yet. The choice of a potent source of MSCs isolated from pediatric donors with consistent differentiation and high proliferation abilities, as well as low immunogenicity, could increase the chance of success for bone allografts. In this study, we employed an immunodeficient animal model humanised with allogeneic immune cells to study the immune responses towards chondrogenically differentiated human pediatric MSCs (ch-pMSCs). We show that ch-differentiated pMSCs remained non-immunogenic to allogeneic CD4 and CD8 T cells in an in vitro co-culture model. After subcutaneous implantation in mice, ch-pMSC-derived grafts were able to initiate bone mineralisation in the presence of an allogeneic immune system for 3 weeks without the onset of immune responses. Re-exposing the splenocytes of the humanised animals to pMSCs did not trigger further T cell proliferation, suggesting an absence of secondary immune responses. Moreover, ch-pMSCs generated mature bone after 8 weeks of implantation that persisted for up to 6 more weeks in the presence of an allogeneic immune system. These data collectively show that human allogeneic chondrogenically differentiated pediatric MSCs might be a safe and potent option for bone defect repair in the tissue engineering and regenerative medicine setting.
MeSH term(s)	Humans ; Mice ; Animals ; Child ; Osteogenesis ; Bone Marrow ; Mesenchymal Stem Cells ; Stromal Cells ; Cell Differentiation ; Hematopoietic Stem Cell Transplantation ; Bone Marrow Cells ; Cells, Cultured
Language	English
Publishing date	2024-01-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2024.122471
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Article ; Online: In Vitro Mineralisation of Tissue-Engineered Cartilage Reduces Endothelial Cell Migration, Proliferation and Tube Formation.

Ji, Encheng / Leijsten, Lieke / Witte-Bouma, Janneke / Rouchon, Adelin / Di Maggio, Nunzia / Banfi, Andrea / van Osch, Gerjo J V M / Farrell, Eric / Lolli, Andrea

Cells

2023 Volume 12, Issue 8

Abstract: Tissue engineering bone via endochondral ossification requires the generation of a cartilage template which undergoes vascularisation and remodelling. While this is a promising route for bone repair, achieving effective cartilage vascularisation remains ... ...

Abstract	Tissue engineering bone via endochondral ossification requires the generation of a cartilage template which undergoes vascularisation and remodelling. While this is a promising route for bone repair, achieving effective cartilage vascularisation remains a challenge. Here, we investigated how mineralisation of tissue-engineered cartilage affects its pro-angiogenic potential. To generate in vitro mineralised cartilage, human mesenchymal stromal cell (hMSC)-derived chondrogenic pellets were treated with β-glycerophosphate (BGP). After optimising this approach, we characterised the changes in matrix components and pro-angiogenic factors by gene expression analysis, histology and ELISA. Human umbilical vein endothelial cells (HUVECs) were exposed to pellet-derived conditioned media, and migration, proliferation and tube formation were assessed. We established a reliable strategy to induce in vitro cartilage mineralisation, whereby hMSC pellets are chondrogenically primed with TGF-β for 2 weeks and BGP is added from week 2 of culture. Cartilage mineralisation determines loss of glycosaminoglycans, reduced expression but not protein abundance of collagen II and X, and decreased VEGFA production. Finally, the conditioned medium from mineralised pellets showed a reduced ability to stimulate endothelial cell migration, proliferation and tube formation. The pro-angiogenic potential of transient cartilage is thus stage-dependent, and this aspect must be carefully considered in the design of bone tissue engineering strategies.
MeSH term(s)	Humans ; Tissue Engineering/methods ; Cartilage/metabolism ; Calcification, Physiologic ; Human Umbilical Vein Endothelial Cells ; Cell Proliferation
Language	English
Publishing date	2023-04-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12081202
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Article: The response of human macrophages to 3D printed titanium antibacterial implants does not affect the osteogenic differentiation of hMSCs.

Garmendia Urdalleta, Amaia / Van Poll, Mathijs / Fahy, Niamh / Witte-Bouma, Janneke / Van Wamel, Willem / Apachitei, Iulian / Zadpoor, Amir A / Fratila-Apachitei, Lidy E / Farrell, Eric

Frontiers in bioengineering and biotechnology

2023 Volume 11, Page(s) 1176534

Abstract: Macrophage responses following the implantation of orthopaedic implants are essential for successful implant integration in the body, partly through intimate crosstalk with human marrow stromal cells (hMSCs) in the process of new bone formation. Additive ...

Abstract	Macrophage responses following the implantation of orthopaedic implants are essential for successful implant integration in the body, partly through intimate crosstalk with human marrow stromal cells (hMSCs) in the process of new bone formation. Additive manufacturing (AM) and plasma electrolytic oxidation (PEO) in the presence of silver nanoparticles (AgNPs) are promising techniques to achieve multifunctional titanium implants. Their osteoimmunomodulatory properties are, however, not yet fully investigated. Here, we studied the effects of implants with AgNPs on human macrophages and the crosstalk between hMSCs and human macrophages when co-cultured
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2023.1176534
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Article ; Online: Cartilage Oligomeric Matrix Protein-Derived Peptides Secreted by Cartilage Do Not Induce Responses Commonly Observed during Osteoarthritis.

Andrés Sastre, Enrique / Zaucke, Frank / Witte-Bouma, Janneke / van Osch, Gerjo J V M / Farrell, Eric

Cartilage

2020 Volume 13, Issue 2_suppl, Page(s) 1229S–1236S

Abstract: Objective: To evaluate if 3 peptides derived from the cartilage oligomeric matrix protein (COMP), which wounded zones of cartilage secrete into synovial fluid, possess biological activity and might therefore be involved in the regulation of specific ... ...

Abstract	Objective: To evaluate if 3 peptides derived from the cartilage oligomeric matrix protein (COMP), which wounded zones of cartilage secrete into synovial fluid, possess biological activity and might therefore be involved in the regulation of specific aspects of joint regeneration. Methods: The 3 peptides were produced by chemical synthesis and then tested Discussion and conclusions: The 3 peptides tested do not regulate TGF-β signaling, angiogenesis and vascular tube formation, or synovial inflammation
MeSH term(s)	Cartilage/metabolism ; Cartilage Oligomeric Matrix Protein ; Cytokines ; Endothelial Cells/metabolism ; Humans ; Osteoarthritis/metabolism
Chemical Substances	Cartilage Oligomeric Matrix Protein ; Cytokines
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2515870-3
ISSN	1947-6043 ; 1947-6035
ISSN (online)	1947-6043
ISSN	1947-6035
DOI	10.1177/1947603520961170
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Article ; Online: Allogeneic Chondrogenic Mesenchymal Stromal Cells Alter Helper T Cell Subsets in CD4+ Memory T Cells.

Kiernan, Caoimhe H / Asmawidjaja, Patrick S / Fahy, Niamh / Witte-Bouma, Janneke / Wolvius, Eppo B / Brama, Pieter A J / Lubberts, Erik / Farrell, Eric

Tissue engineering. Part A

2020 Volume 26, Issue 9-10, Page(s) 490–502

Abstract: Implantation of chondrogenically differentiated mesenchymal stromal cells (MSCs) leads to bone ... ...

Abstract	Implantation of chondrogenically differentiated mesenchymal stromal cells (MSCs) leads to bone formation
MeSH term(s)	CD4-Positive T-Lymphocytes/metabolism ; Cell Differentiation/physiology ; Cells, Cultured ; Chondrogenesis/genetics ; Chondrogenesis/physiology ; Coculture Techniques ; Humans ; Interleukin-6/metabolism ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism ; T-Lymphocytes, Helper-Inducer/metabolism
Chemical Substances	Interleukin-6
Language	English
Publishing date	2020-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.TEA.2019.0177
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Article ; Online: Chondrogenically Primed Human Mesenchymal Stem Cells Persist and Undergo Early Stages of Endochondral Ossification in an Immunocompetent Xenogeneic Model.

Fahy, Niamh / Palomares Cabeza, Virginia / Lolli, Andrea / Witte-Bouma, Janneke / Merino, Ana / Ridwan, Yanto / Wolvius, Eppo B / Hoogduijn, Martin J / Farrell, Eric / Brama, Pieter A J

Frontiers in immunology

2021 Volume 12, Page(s) 715267

Abstract: Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the ... ...

Abstract	Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the process of endochondral ossification and form mature bone
MeSH term(s)	Animals ; Biomarkers ; Bone Regeneration ; Calcification, Physiologic ; Cell Differentiation/genetics ; Cells, Cultured ; Chondrogenesis/genetics ; Humans ; Immunity ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice ; Models, Animal ; Monocytes/immunology ; Monocytes/metabolism ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Tissue Engineering ; X-Ray Microtomography
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-09-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.715267
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Article: Pediatric Mesenchymal Stem Cells Exhibit Immunomodulatory Properties Toward Allogeneic T and B Cells Under Inflammatory Conditions.

Palomares Cabeza, Virginia / Hoogduijn, Martin Johannes / Kraaijeveld, Rens / Franquesa, Marcella / Witte-Bouma, Janneke / Wolvius, Eppo B / Farrell, Eric / Brama, Pieter A J

Frontiers in bioengineering and biotechnology

2019 Volume 7, Page(s) 142

Abstract: Mesenchymal stem cells from pediatric patients (pMSCs) are an attractive cell source in regenerative medicine, due to their higher proliferation rates and better differentiation abilities compared to adult MSCs (aMSCs). We have previously characterized ... ...

Abstract	Mesenchymal stem cells from pediatric patients (pMSCs) are an attractive cell source in regenerative medicine, due to their higher proliferation rates and better differentiation abilities compared to adult MSCs (aMSCs). We have previously characterized the immunomodulatory abilities of pMSCs on T cells under co-culture. It has also been reported that aMSCs can inhibit B cell proliferation and maturation under inflammatory conditions. In this study, we therefore aimed to clarify the immunomodulatory effect of pMSCs toward T and B cells in an inflammatory microenvironment. Bone marrow derived pMSCs were primed to simulate inflammatory conditions by exposure with 50 ng/mL of IFN-γ for 3 days. To analyze the interaction between pMSCs and T cells, CD3/CD28 stimulated peripheral blood mononuclear cells (PBMCs) were co-cultured with primed or unprimed pMSCs. To investigate B cell responses, quiescent B cells obtained from spleens by CD43 negative selection were stimulated with anti-IgM, anti-CD40, IL-2, and co-cultured with either IFN-γ primed or unprimed pMSC. pMSC phenotype, B and T cell proliferation, and B cell functionality were analyzed. Gene expression of indoleamine 2,3-dioxygenease (IDO), as well as the expression of HLA-ABC, HLA-DR and the co-stimulatory molecules CD80 and CD86 was upregulated on pMSCs upon IFN-γ priming. IFN-γ did not alter the immunomodulatory abilities of pMSCs upon CD4
Language	English
Publishing date	2019-06-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2019.00142
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Article ; Online: Bio-inspired polymeric iron-doped hydroxyapatite microspheres as a tunable carrier of rhBMP-2.

Fernandes Patrício, Tatiana M / Mumcuoglu, Didem / Montesi, Monica / Panseri, Silvia / Witte-Bouma, Janneke / Garcia, Shorouk Fahmy / Sandri, Monica / Tampieri, Anna / Farrell, Eric / Sprio, Simone

Materials science & engineering. C, Materials for biological applications

2020 Volume 119, Page(s) 111410

Abstract: Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in ... ...

Abstract	Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release profiles. The comparison with hybrid non-magnetic and with non-mineralized microspheres highlights the role of nanocrystalline, nanosize mineral phases when they exhibit surface charged groups enabling the chemical linking with the growth factor and thus moderating the release kinetics. All the microspheres show excellent osteogenic ability with human mesenchymal stem cells whereas the hybrid mineralized ones show a slow and sustained release of rhBMP-2 along 14 days of soaking into cell culture medium with substantially bioactive effect, as reported by assay with C2C12 BRE-Luc cell line. It is also shown that the release extent can be modulated by the application of pulsed electromagnetic field, thus showing the potential of remote controlling the bioactivity of the new micro-devices which is promising for future application of hybrid biomimetic microspheres in precisely designed and personalized therapies.
MeSH term(s)	Bone Morphogenetic Protein 2 ; Bone Regeneration ; Durapatite ; Humans ; Iron ; Microspheres ; Osteogenesis ; Recombinant Proteins ; Transforming Growth Factor beta
Chemical Substances	Bone Morphogenetic Protein 2 ; Recombinant Proteins ; Transforming Growth Factor beta ; recombinant human bone morphogenetic protein-2 ; Durapatite (91D9GV0Z28) ; Iron (E1UOL152H7)
Language	English
Publishing date	2020-08-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012160-X
ISSN	1873-0191 ; 0928-4931
ISSN (online)	1873-0191
ISSN	0928-4931
DOI	10.1016/j.msec.2020.111410
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Article: Data on the surface morphology of additively manufactured Ti-6Al-4V implants during processing by plasma electrolytic oxidation

van Hengel, Ingmar A.J. / Riool, Martijn / Fratila-Apachitei, Lidy E. / Witte-Bouma, Janneke / Farrell, Eric / Zadpoor, Amir A. / Zaat, Sebastian A.J. / Apachitei, Iulian

Data in Brief. 2017 Aug., v. 13

2017

Abstract: Additively manufactured Ti-6Al-4V implants were biofunctionalized using plasma electrolytic oxidation. At various time points during this process scanning electron microscopy imaging was performed to analyze the surface morphology (van Hengel et al., ... ...

Abstract	Additively manufactured Ti-6Al-4V implants were biofunctionalized using plasma electrolytic oxidation. At various time points during this process scanning electron microscopy imaging was performed to analyze the surface morphology (van Hengel et al., 2017) [1]. This data shows the changes in surface morphology during plasma electrolytic oxidation. Data presented in this article are related to the research article “Selective laser melting porous metallic implants with immobilized silver nanoparticles kill and prevent biofilm formation by methicillin-resistant Staphylococcus aureus” (van Hengel et al., 2017) [1].
Keywords	biofilm ; methicillin-resistant Staphylococcus aureus ; nanosilver ; oxidation
Language	English
Dates of publication	2017-08
Size	p. 385-389.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2017.06.015
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Article ; Online: Isolating Pediatric Mesenchymal Stem Cells with Enhanced Expansion and Differentiation Capabilities.

Knuth, Callie An / Kiernan, Caoimhe H / Palomares Cabeza, Virginia / Lehmann, Johannes / Witte-Bouma, Janneke / Ten Berge, Derk / Brama, Pieter A / Wolvius, Eppo B / Strabbing, Elske M / Koudstaal, Maarten J / Narcisi, Roberto / Farrell, Eric

Tissue engineering. Part C, Methods

2018 Volume 24, Issue 6, Page(s) 313–321

Abstract: Mesenchymal stem cells/marrow stromal cells (MSCs) are attractive for applications ranging from research and development to use in clinical therapeutics. However, the most commonly studied MSCs, adult bone marrow MSCs (A-MSCs), are limited by significant ...

Abstract	Mesenchymal stem cells/marrow stromal cells (MSCs) are attractive for applications ranging from research and development to use in clinical therapeutics. However, the most commonly studied MSCs, adult bone marrow MSCs (A-MSCs), are limited by significant donor variation resulting in inconsistent expansion rates and multilineage differentiation capabilities. We have recently obtained permission to isolate pediatric MSCs (P-MSCs) from surplus iliac crest bone chips. Here, we developed a simple and easily replicable isolation protocol yielding P-MSCs, which adhere to MSC defining guidelines. After confirming immunophenotypic marker expression, we compared expansion rates, senescence, morphology, and trilineage differentiation of P-MSCs to A-MSCs for multiple donors. We found P-MSCs have faster in vitro replication, consistently show significantly lower senescence, and are capable of more reproducible multilineage differentiation than A-MSCs. We, therefore, believe P-MSCs are a promising candidate for use in research applications and potentially as part of an allogeneic therapeutic treatment.
MeSH term(s)	Adult ; Bone Marrow Cells/cytology ; Cell Culture Techniques ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Child ; Humans ; Male ; Mesenchymal Stem Cells/cytology
Language	English
Publishing date	2018-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2420585-0
ISSN	1937-3392 ; 1937-3384
ISSN (online)	1937-3392
ISSN	1937-3384
DOI	10.1089/ten.TEC.2018.0031
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