Human iPSC-derived iMSCs improve bone regeneration in mini-pigs.

Bone Bone quality and biomechanics

Journal

Bone research
ISSN: 2095-4700
Titre abrégé: Bone Res
Pays: China
ID NLM: 101608652

Informations de publication

Date de publication:
2019
Historique:
received: 22 10 2018
revised: 04 06 2019
accepted: 22 07 2019
entrez: 1 11 2019
pubmed: 2 11 2019
medline: 2 11 2019
Statut: epublish

Résumé

Autologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts (HFFs). They were able to differentiate into osteoblasts in vitro, express a plethora of bone morphogenic proteins (BMPs) and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. Radiologically and histomorphometrically, HFF-iMSC + CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC + CPG after 6 weeks. The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans.

Identifiants

pubmed: 31667001
doi: 10.1038/s41413-019-0069-4
pii: 69
pmc: PMC6813363
doi:

Types de publication

Journal Article

Langues

eng

Pagination

32

Informations de copyright

© The Author(s) 2019.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare no competing interests.

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Auteurs

Pascal Jungbluth (P)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Lucas-Sebastian Spitzhorn (LS)

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Jan Grassmann (J)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Stephan Tanner (S)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

David Latz (D)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Md Shaifur Rahman (MS)

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Martina Bohndorf (M)

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Wasco Wruck (W)

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Martin Sager (M)

3Animal Research Institute, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Vera Grotheer (V)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Patric Kröpil (P)

4Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Mohssen Hakimi (M)

5Vivantes Klinikum Am Urban, Dieffenbachstraße 1, 10967 Berlin, Germany.

Joachim Windolf (J)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Johannes Schneppendahl (J)

1Department of Trauma and Hand Surgery, Heinrich Heine University Hospital Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

James Adjaye (J)

2Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.

Classifications MeSH