Bone Regeneration With Osteogenically Enhanced Mesenchymal Stem Cells and Their Extracellular Matrix Proteins

Clough, Bret H.; McCarley, Matthew R.; Krause, U.; Zeitouni, Suzanne; Froese, Jeremiah J; McNeill, Eoin P.; Chaput, Christopher D.; Sampson, H. Wayne; Gregory, Carl A.

doi:10.1002/jbmr.2320

Cited by 44 publications

(74 citation statements)

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“…Recently, we confirmed that OEhMSCs do not inherently activate proliferation of immunologically mismatched lymphocytes [52], but it was unclear whether lymphocyte exposure had a detrimental effect on OEhMSC viability. To address this question, GFP-labeled OEhMSCs were attached to BGS and exposed to immunologically mismatched PBMNCs.…”

Section: Resultsmentioning

confidence: 99%

“…Osteogenically enhanced human mesenchymal stem cells were generated by culture for 8 days in the presence of 10 μM GW9662 and osteogenic supplementation, as previously described [50–52]. …”

Section: Methodsmentioning

confidence: 99%

“…Bioconditioned gelatin sponge was generated by growth of OEhMSCs on clinical-grade Gelfoam (Pfizer, NY, USA or Ethicon, NJ, USA) followed by decellularization, as previously described [52]. …”

Section: Methodsmentioning

confidence: 99%

“…After microcomputed tomography (μCT) scanning, spines were fixed, decalcified, embedded, and sectioned using standard techniques [52]. Masson trichrome staining was performed using a commercially acquired kit (American MasterTech Scientific Inc., Lodi, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Using this approach, we have generated a form of hMSC that has enhanced osteogenic potential (hereafter referred to as osteogenically enhanced hMSCs, or OEhMSCs) and the enhanced capacity to generate substantial amounts of extracellular matrix (ECM) containing a cocktail of collagen types found primarily in anabolic bone tissue. When the ECM is combined with the OEhMSCs, the material has excellent osteogenic capacity and thus could serve as an effective replacement for bone graft [51,52]. …”

Section: Introductionmentioning

confidence: 99%

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An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

et al. 2017

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BACKGROUND CONTEXT Spine pain and the disability associated with it are epidemic in the United States. According to the National Center for Health Statistics, more than 650,000 spinal fusion surgeries are performed annually in the United States, and yet there is a failure rate of 15%–40% when standard methods employing current commercial bone substitutes are used. Autologous bone graft is the gold standard in terms of fusion success, but the morbidity associated with the procedure and the limitations in the availability of sufficient material have limited its use in the majority of cases. A freely available and immunologically compatible bone mimetic with the properties of live tissue is likely to substantially improve the outcome of spine fusion procedures without the disadvantages of autologous bone graft. PURPOSE This study aimed to compare a live human bone tissue analog with autologous bone grafting in an immunocompromised rat model of posterolateral fusion. DESIGN/SETTING This is an in vitro and in vivo preclinical study of a novel human stem cell–derived construct for efficacy in posterolateral lumbar spine fusion. METHODS Osteogenically enhanced human mesenchymal stem cells (OEhMSCs) were generated by exposure to conditions that activate the early stages of osteogenesis. Immunologic characteristics of OEhMSCs were evaluated in vitro. The secreted extracellular matrix from OEhMSCs was deposited on a clinical-grade gelatin sponge, resulting in bioconditioned gelatin sponge (BGS). Bioconditioned gelatin sponge was used alone, with live OEhMSCs (BGS+OEhMSCs), or with whole human bone marrow (BGS+hBM). Efficacy for spine fusion was determined by an institutionally approved animal model using 53 nude rats. RESULTS Bioconditioned gelatin sponge with live OEhMSCs did not cause cytotoxicity when incubated with immunologically mismatched lymphocytes, and OEhMSCs inhibited lymphocyte expansion in mixed lymphocyte assays. Bioconditioned gelatin sponge with live OEhMSC and BGS+hBM constructs induced profound bone growth at fusion sites in vivo, with a comparable rate of fusion with syngeneic bone graft (negative [0 of 10], BGS alone [0 of 10], bone graft [7 of 10], BGS+OEhMSC [10 of 15], and BGS+hBM [8 of 8]). CONCLUSIONS Collectively, these studies demonstrate that BGS+OEhMSC constructs possess low immunogenicity and drive vertebral fusion with efficiency matching syngeneic bone graft in rodents. We also demonstrate that BGS serves as a promising scaffold for spine fusion when combined with hBM.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

et al. 2017

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Conditioning of 3D Printed Nanoengineered Ionic–Covalent Entanglement Scaffolds with iP‐hMSCs Derived Matrix

Sears

Mondragón

Richards

et al. 2020

Adv Healthcare Materials

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Additive manufacturing is a promising method for producing customized three-dimensional (3D) bioactive constructs for regenerative medicine. Here, we report 3D printed highly osteogenic scaffolds using nanoengineered ionic-covalent entanglement ink (NICE) for bone tissue engineering. This NICE ink consists of ionic-covalent entanglement reinforced with Laponite, a two-dimensional (2D) nanosilicate (nSi) clay, allowing for the printing of anatomic-sized constructs with high accuracy. In addition, the 3D printed structure is able to maintain high structural stability in physiological conditions without any significant swelling or deswelling. While the presence of nSi imparts osteoinductive characteristics to the NICE scaffolds, this was further augmented by depositing pluripotent stem cellderived extracellular matrix (ECM) on the surface of the scaffolds. This was achieved by stimulating human induced pluripotent stem cell-derived mesenchymal stem cells (iP-hMSCs) with 2-chloro-5nitrobenzanilide, a PPARγ inhibitor that enhances Wnt pathway, resulting in the deposition of an ECM characterized by high levels of collagens VI and XII found in anabolic bone. The osteoinductive characteristics of these bioconditioned NICE (bNICE) scaffolds is demonstrated through osteogenic differentiation of bone marrow derived human mesenchymal stem cells (hMSCs). A significant increase in the expression of osteogenic gene markers including bone morphogenic protein-2, osteocalcin and osteopontin was observed on ECM-coated scaffolds compared to bare scaffolds, as well as improved mineralization. This approach of augmenting the bioactivity of 3D printed scaffolds by depositing an anabolic bone ECM will provide a unique strategy to design personalized bone graft geometries for in situ bone regeneration.Received: ((will be filled in by the editorial staff))Revised: ((will be filled in by the editorial staff))

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Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides

Toosi

Behravan

2019

BioFactors

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Bone is one of the most frequently transplanted tissues. The bone structure and its physiological function and stem cells biology were known to be closely related to each other for many years. Bone is considered a home to the well‐known systems of postnatal mesenchymal stem cells (MSCs). These bone resident MSCs provide a range of growth factors (GF) and cytokines to support cell growth following injury. These GFs include a group of proteins and peptides produced by different cells which are regulators of important cell functions such as division, migration, and differentiation. GF signaling controls the formation and development of the MSCs condensation and plays a critical role in regulating osteogenesis, chondrogenesis, and bone/mineral homeostasis. Thus, a combination of both MSCs and GFs receives high expectations in regenerative medicine, particularly in bone repair applications. It is known that the delivery of exogenous GFs to the non‐union bone fracture site remarkably improves healing results. Here we present updated information on bone tissue engineering with a specific focus on GF characteristics and their application in cellular functions and tissue healing. Moreover, the interrelation of GFs with the damaged bone microenvironment and their mechanistic functions are discussed.

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Bone Regeneration With Osteogenically Enhanced Mesenchymal Stem Cells and Their Extracellular Matrix Proteins

Cited by 44 publications

References 40 publications

An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses

Conditioning of 3D Printed Nanoengineered Ionic–Covalent Entanglement Scaffolds with iP‐hMSCs Derived Matrix

Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides

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