Engineering of a functional bone organ through endochondral ossification.
Celeste Scotti,Elia Piccinini,Hitoshi Takizawa,Atanas Todorov,Paul Bourgine,Adam Papadimitropoulos,Andrea Barbero,Markus G. Manz,Ivan Martin +8 more
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TLDR
The generation by appropriately instructed hMSC of an ectopic “bone organ” with a size, structure, and functionality comparable to native bones is reported, providing a model useful for fundamental and translational studies of bone morphogenesis and regeneration, as well as for the controlled manipulation of hematopoietic stem cell niches in physiology and pathology.Abstract:
Embryonic development, lengthening, and repair of most bones proceed by endochondral ossification, namely through formation of a cartilage intermediate. It was previously demonstrated that adult human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) can execute an endochondral program and ectopically generate mature bone. Here we hypothesized that hMSCs pushed through endochondral ossification can engineer a scaled-up ossicle with features of a “bone organ,” including physiologically remodeled bone, mature vasculature, and a fully functional hematopoietic compartment. Engineered hypertrophic cartilage required IL-1β to be efficiently remodeled into bone and bone marrow upon subcutaneous implantation. This model allowed distinguishing, by analogy with bone development and repair, an outer, cortical-like perichondral bone, generated mainly by host cells and laid over a premineralized area, and an inner, trabecular-like, endochondral bone, generated mainly by the human cells and formed over the cartilaginous template. Hypertrophic cartilage remodeling was paralleled by ingrowth of blood vessels, displaying sinusoid-like structures and stabilized by pericytic cells. Marrow cavities of the ossicles contained phenotypically defined hematopoietic stem cells and progenitor cells at similar frequencies as native bones, and marrow from ossicles reconstituted multilineage long-term hematopoiesis in lethally irradiated mice. This study, by invoking a “developmental engineering” paradigm, reports the generation by appropriately instructed hMSC of an ectopic “bone organ” with a size, structure, and functionality comparable to native bones. The work thus provides a model useful for fundamental and translational studies of bone morphogenesis and regeneration, as well as for the controlled manipulation of hematopoietic stem cell niches in physiology and pathology.read more
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Bone marrow–on–a–chip replicates hematopoietic niche physiology in vitro
Yu Suke Torisawa,Catherine S. Spina,Tadanori Mammoto,Akiko Mammoto,James C. Weaver,Tracy Tat,James J. Collins,Donald E. Ingber +7 more
TL;DR: A method for fabricating 'bone marrow–on–a–chip' that permits culture of living marrow with a functional hematopoietic niche in vitro by first engineering new bone in vivo, removing it whole and perfusing it with culture medium in a microfluidic device is described.
Journal ArticleDOI
Bone physiology as inspiration for tissue regenerative therapies.
TL;DR: A systematic parallelization of fundamental well-established biology of bone, updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and critical discussion of how individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches are suggested.
Journal ArticleDOI
Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects.
TL;DR: This review focuses on the recent advances in bone tissue engineering, specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects.
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3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering
TL;DR: This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma‐irradiated alginate bioink incorporating Arg‐Gly‐Asp adhesion peptides, and can be reinforced with a network of printed polycaprolactone fibers, resulting in a ≈350 fold increase in construct compressive modulus.
Journal ArticleDOI
Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation
Andreas Reinisch,Andreas Reinisch,Nathalie Etchart,Daniel Thomas,Nicole A. Hofmann,Margareta Fruehwirth,Subarna Sinha,Charles Chan,Kshemendra Senarath-Yapa,Eun Young Seo,Taylor Wearda,Udo F. Hartwig,Christine Beham-Schmid,Slave Trajanoski,Qiong Lin,Wolfgang Wagner,Christian Dullin,Frauke Alves,Frauke Alves,Michael Andreeff,Irving L. Weissman,Michael T. Longaker,Katharina Schallmoser,Katharina Schallmoser,Ravindra Majeti,Dirk Strunk,Dirk Strunk +26 more
TL;DR: A genome-wide methylation, transcription, and in vivo evaluation of MSCs from human bone marrow, white adipose tissue, umbilical cord, and skin is performed and a tractable human niche model for studying homing and engraftment of human hematopoietic cells in normal and neoplastic states is demonstrated.
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