Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells

J. Bolander, W. Ji, Jeroen Christianus Hermanus Leijten, Liliana Moreira Teixeira, Veerle Bloemen, D. Lambrechts, M. Chaklader, F.P. Luyten

  • 4 Citations

Abstract

Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.
Original languageEnglish
Pages (from-to)758–772
JournalStem cell reports
Volume8
Issue number3
DOIs
StatePublished - 14 Mar 2017

Fingerprint

Periosteum
Bone Morphogenetic Protein 2
Bone and Bones
Serum
Biomimetics
Regenerative Medicine
Osteogenesis
Cartilage
Stem Cells
In Vitro Techniques

Keywords

  • IR-103561
  • METIS-321601

Cite this

Bolander, J., Ji, W., Leijten, J. C. H., Moreira Teixeira, L., Bloemen, V., Lambrechts, D., ... Luyten, F. P. (2017). Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells. Stem cell reports, 8(3), 758–772. DOI: 10.1016/j.stemcr.2017.01.005

Bolander, J.; Ji, W.; Leijten, Jeroen Christianus Hermanus; Moreira Teixeira, Liliana; Bloemen, Veerle; Lambrechts, D.; Chaklader, M.; Luyten, F.P. / Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells.

In: Stem cell reports, Vol. 8, No. 3, 14.03.2017, p. 758–772.

Research output: Scientific - peer-reviewArticle

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abstract = "Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.",
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Bolander, J, Ji, W, Leijten, JCH, Moreira Teixeira, L, Bloemen, V, Lambrechts, D, Chaklader, M & Luyten, FP 2017, 'Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells' Stem cell reports, vol 8, no. 3, pp. 758–772. DOI: 10.1016/j.stemcr.2017.01.005

Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells. / Bolander, J.; Ji, W.; Leijten, Jeroen Christianus Hermanus; Moreira Teixeira, Liliana; Bloemen, Veerle; Lambrechts, D.; Chaklader, M.; Luyten, F.P.

In: Stem cell reports, Vol. 8, No. 3, 14.03.2017, p. 758–772.

Research output: Scientific - peer-reviewArticle

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T1 - Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells

AU - Bolander,J.

AU - Ji,W.

AU - Leijten,Jeroen Christianus Hermanus

AU - Moreira Teixeira,Liliana

AU - Bloemen,Veerle

AU - Lambrechts,D.

AU - Chaklader,M.

AU - Luyten,F.P.

N1 - Open access. In Press, Corrected Proof

PY - 2017/3/14

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N2 - Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.

AB - Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2). Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.

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Bolander J, Ji W, Leijten JCH, Moreira Teixeira L, Bloemen V, Lambrechts D et al. Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells. Stem cell reports. 2017 Mar 14;8(3):758–772. Available from, DOI: 10.1016/j.stemcr.2017.01.005