Mesenchymal Stem Cells Expressing Insulin‐like Growth Factor‐I (MSCIGF) Promote Fracture Healing and Restore New Bone Formation in Irs1 Knockout Mice: Analyses of MSCIGF Autocrine and Paracrine Regenerative Effects
Froilán Granero-Moltó,Timothy J. Myers,Jared A. Weis,Lara Longobardi,Tieshi Li,Yun Yan,Natasha Case,Janet Rubin,Anna Spagnoli +8 more
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It was found that systemically transplanted MSCIGF through autocrine and paracrine actions improved the fracture mechanical strength and increased new bone content while accelerating mineralization and it was determined that IGF‐I adapted the response of transplants MSCigF to promote their differentiation into osteoblasts.Abstract:
Failures of fracture repair (nonunions) occur in 10% of all fractures. The use of mesenchymal stem cells (MSC) in tissue regeneration appears to be rationale, safe, and feasible. The contributions of MSC to the reparative process can occur through autocrine and paracrine effects. The primary objective of this study is to find a novel mean, by transplanting primary cultures of bone marrow-derived MSCs expressing insulin-like growth factor-I (MSC(IGF)), to promote these seed-and-soil actions of MSC to fully implement their regenerative abilities in fracture repair and nonunions. MSC(IGF) or traceable MSC(IGF)-Lac-Z were transplanted into wild-type or insulin-receptor-substrate knockout (Irs1(-/-)) mice with a stabilized tibia fracture. Healing was assessed using biomechanical testing, microcomputed tomography (μCT), and histological analyses. We found that systemically transplanted MSC(IGF) through autocrine and paracrine actions improved the fracture mechanical strength and increased new bone content while accelerating mineralization. We determined that IGF-I adapted the response of transplanted MSC(IGF) to promote their differentiation into osteoblasts. In vitro and in vivo studies showed that IGF-I-induced osteoglastogenesis in MSCs was dependent of an intact IRS1-PI3K signaling. Furthermore, using Irs1(-/-) mice as a nonunion fracture model through altered IGF signaling, we demonstrated that the autocrine effect of IGF-I on MSC restored the fracture new bone formation and promoted the occurrence of a well-organized callus that bridged the gap. A callus that was basically absent in Irs1(-/-) left untransplanted or transplanted with MSCs. We provided evidence of effects and mechanisms for transplanted MSC(IGF) in fracture repair and potentially to treat nonunions.read more
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Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model
Taisuke Furuta,Shigeru Miyaki,Hiroyuki Ishitobi,Toshihiko Ogura,Yoshio Kato,Naosuke Kamei,Kenji Miyado,Yukihito Higashi,Mitsuo Ochi +8 more
TL;DR: Exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process and suggest that exosomes in CM facilitate the acceleration of fracture healing.
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The key regulatory roles of the PI3K/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration.
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Nanoparticles and their potential for application in bone.
TL;DR: This review will highlight potential nanoparticle applications in bone, focusing on cell labeling as well as drug and gene delivery, which could lead to new therapeutic strategies to improve bone regeneration or to treat bone disorders.
The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration
TL;DR: A review of the literature related to the roles of the PI3K/Akt pathway in the functionalities of mesenchymal stem cells and the involvement of the pathway in biomaterials-increased MSC functinalities is presented in this paper.
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Silver nanoparticles promote osteogenesis of mesenchymal stem cells and improve bone fracture healing in osteogenesis mechanism mouse model
Ruizhong Zhang,PY Lee,Vincent C.H. Lui,Yan Chen,Xuelai Liu,Chun-Nam Lok,Michael To,Kelvin W.K. Yeung,Kenneth K. Y. Wong +8 more
TL;DR: A novel application is demonstrated in that these nanoparticles were efficient in promoting osteoblastic differentiation in both in-vitro and in- vivo studies, which may provide a new treatment direction for bone fracture in the future.
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