Reengineering autologous bone grafts with the stem cell activator WNT3A

Wei, Jing; Smith, Andrew A.; Liu, Bo; Li, Jingtao; Hunter, Daniel J.; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Corey W.; Chen, Serafine; Lee, Katherine; Singh, Gurdev; Helms, Jill A.

doi:10.1016/j.biomaterials.2014.12.014

Cited by 44 publications

(63 citation statements)

References 84 publications

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“…Although reports of tissue engineering have been centered on the promotion of osteogenic (e.g. Wnt) [180] or vascular (e.g. VEGF) [181] pathways, a growing number of reports involve modulating inflammation to improve tissue [90, 182, 183] and bone repair by biomimetic approaches [70, 94, 96].…”

Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

“…Thus, there are new opportunities to “re-engineer” the current constructs by the functionalization of scaffolds and by direct cell delivery. The functionalization of scaffolds may involve controlled release of biologics to extend their bioactivity, the recruitment and differentiation of autologous stem cells, the local, temporal control of biologics, and to couple scaffold degradation with new bone growth [180, 184–186]. A more recent approach is to reproduce the sequential release of polarizing macrophage factors, that promote the classical activation into M1-macrophage during the first 24 hours (e.g.…”

Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

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Inflammation, fracture and bone repair

Loi

Córdova

Pajarinen

et al. 2016

Bone

866

807

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The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair.

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Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

Section: Opportunities For Enhancing Bone Repair By Modulating Infmentioning

confidence: 99%

Inflammation, fracture and bone repair

Loi

Córdova

Pajarinen

et al. 2016

Bone

866

807

View full text Add to dashboard Cite

show abstract

“…Both DMPC and DOPC lipids are in a liquid crystalline form at body temperature (which we and other have found to be necessary for Wnt association with liposomes [39]), but DMPC and DOPC differ in their size and saturation -DMPC has a saturated 14 carbon acyl tail, while DOPC is longer (18 carbons) and is monounsaturated. Wnt3A is modified with palmitoleic acid at Ser209 and palmitate at Cys77 [40] (although the relevance of the latter modification in vivo has recently been disputed [41]).…”

Section: Discussionmentioning

confidence: 99%

PEGylated liposomes associate with Wnt3A protein and expand putative stem cells in human bone marrow populations

et al. 2017

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Aim:To fabricate PEGylated liposomes which preserve the activity of hydrophobic Wnt3A protein, and to demonstrate their efficacy in promoting expansion of osteoprogenitors from human bone marrow. Methods: PEGylated liposomes composed of several synthetic lipids were tested for their ability to preserve Wnt3A activity in reporter and differentiation assays. Single-molecule microspectroscopy was used to test for direct association of protein with liposomes. Results: Labeled Wnt3A protein directly associated with all tested liposome preparations. However, Wnt3A activity was preserved or enhanced in PEGylated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes but not in PEGylated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. PEGylated Wnt3A liposomes associated with skeletal stem cell populations in human bone marrow and promoted osteogenesis. Conclusion: Active Wnt protein-containing PEGylated liposomes may have utility for systemic administration for bone repair.

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“…In addition, bone tissue engineering can be more unreliable in aging patients, due to age-related changes in the regenerative niche [82]. Helms and colleagues demonstrated that replenishment of Wnt3a signaling in bioengineered autografts resulted in superior bone forming capacity compared to standard of care in an aged mouse spinal fusion model[83]. By further exploring the stem cell niche environments of the skeleton, researchers can also develop novel strategies to re-create a niche microenvironment for the implanted stem and progenitor cells, which will hopefully increase stem cell viability and contribution to bone regeneration.…”

Section: Looking To the Future: Understanding And Manipulating The Stmentioning

confidence: 99%

Stem and progenitor cells: advancing bone tissue engineering

Tevlin

Walmsley

Marecic

et al. 2015

Drug Deliv. and Transl. Res.

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Background Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic and prosthetic materials. Autologous bone—the best option—is limited in supply, and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. Methods A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. Results In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Conclusion Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell based therapies in the past decade.

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Reengineering autologous bone grafts with the stem cell activator WNT3A

Cited by 44 publications

References 84 publications

Inflammation, fracture and bone repair

Inflammation, fracture and bone repair

PEGylated liposomes associate with Wnt3A protein and expand putative stem cells in human bone marrow populations

Stem and progenitor cells: advancing bone tissue engineering

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