3D Culture of Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) Could Improve Bone Regeneration in 3D-Printed Porous Ti6Al4V Scaffolds

Yu, Lingjia; Wu, Yuanhao; Liu, Jieying; Li, Bo; Ma, Bupeng; Li, Yaqian; Huang, Zhenfei; He, Yu; Wang, Hai; Wu, Zhihong; Qiu, Guixing

doi:10.1155/2018/2074021

Cited by 35 publications

(21 citation statements)

References 40 publications

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“…However, despite such a short time, after postmortem examination, it can be concluded that the scaffolds with injected cells have become more integrated with the skull bones than the empty skeleton alone, which may result from the formation of cartilage, impossible to visualize in computed tomography. Similar results were described for maxillary sinus elevation with different bone substitutes and BMSCs [38], although the low survival rate of grafted BMSCs was reported, which resulted from acute inflammation and mechanical damage [39] and indisposed to use the therapy in a clinic.…”

supporting

confidence: 66%

Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord

Kosinski

Figiel-Dabrowska

Lech

et al. 2020

Stem Cells International

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Objective. Bone defects or atrophy may arise as a consequence of injury, inflammation of various etiologies, and neoplastic or traumatic processes or as a result of surgical procedures. Sometimes the regeneration process of bone loss is impaired, significantly slowed down, or does not occur, e.g., in congenital defects. For the bone defect reconstruction, a piece of the removed bone from ala of ilium or bone transplantation from a decedent is used. Replacement of the autologous or allogenic source of the bone-by-bone substitute could reduce the number of surgeries and time in the pharmacological coma during the reconstruction of the bone defect. Application of mesenchymal stem cells in the reconstruction surgery may have positive influence on tissue regeneration by secretion of angiogenic factors, recruitment of other MSCs, or differentiation into osteoblasts. Materials and Methods. Mesenchymal stem cells derived from the umbilical cord (Wharton’s jelly (WJ-MSC)) were cultured in GMP-grade DMEM low glucose supplemented with heparin, 10% platelet lysate, glucose, and antibiotics. In vitro WJ-MSCs were seeded on the bone substitute Bio-Oss Collagen® and cultured in the StemPro® Osteogenesis Differentiation Kit. During the culture on the 1st, 7th, 14th, and 21st day (day in vitro (DIV)), we analyzed viability (confocal microscopy) and adhesion capability (electron microscopy) of WJ-MSC on Bio-Oss scaffolds, gene expression (qPCR), and secretion of proteins (Luminex). In vivo Bio-Oss® scaffolds with WJ-MSC were transplanted to trepanation holes in the cranium to obtain their overgrowth. The computed tomography was performed 7, 14, and 21 days after surgery to assess the regeneration. Results. The Bio-Oss® scaffold provides a favourable environment for WJ-MSC survival. WJ-MSCs in osteodifferentiation medium are able to attach and proliferate on Bio-Oss® scaffolds. Results obtained from qPCR and Luminex® indicate that WJ-MSCs possess the ability to differentiate into osteoblast-like cells and may induce osteoclastogenesis, angiogenesis, and mobilization of host MSCs. In animal studies, WJ-MSCs seeded on Bio-Oss® increased the scaffold integration with host bone and changed their morphology to osteoblast-like cells. Conclusions. The presented construct consisted of Bio-Oss®, the scaffold with high flexibility and plasticity, approved for clinical use with seeded immunologically privileged WJ-MSC which may be considered reconstructive therapy in bone defects.

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supporting

confidence: 66%

Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord

Kosinski

Figiel-Dabrowska

Lech

et al. 2020

Stem Cells International

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“…In addition to collagen, poly( l -lactic acid) and blends of these materials, Matrigel, a hydrogel mainly composed of type IV collagens, entactin, perlecan and laminin has been shown to increase the osteogenic differentiation potential compared to 2D cell culture. If differentiated within a Matrigel scaffold, human BM-MSCs showed higher activity of alkaline phosphatase (an early marker of osteogenesis) compared to the 2D counterparts [ 90 ]. In addition, Alizarin Red S staining revealed higher Ca 2+ deposition in cells differentiated in 3D.…”

Section: Impact Of 3d Cell Culture On Bone Regeneration-relevant Propmentioning

confidence: 99%

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

2021

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As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.

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“…tubular complex structures in the presence of proper angiogenic and extracellular matrix mediators (Shen et al, 2015;Yu et al, 2018). To evaluate the involvement of TNFR2 in this regenerative feature, WT and TNFR2 KO-MSCs were cultured on Matrigel using either DMEM standard medium or EC growth medium (EGM2) containing a variety of pro-angiogenic FIGURE 4 | The expression of TNFR2 by mesenchymal stem cells (MSCs) is correlated to their higher NO production.…”

Section: Expression Of Tnfr2 By Mesenchymal Stem Cells Influences Thementioning

confidence: 99%

TNFR2 Is a Crucial Hub Controlling Mesenchymal Stem Cell Biological and Functional Properties

Beldi

Bahiraii

Lezin

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSCs) have drawn lots of attention as gold standard stem cells in fundamental and clinical researches during the last 20 years. Due to their tissue and vascular repair capacities, MSCs have been used to treat a variety of degenerative disorders. Moreover, MSCs are able to modulate immune cells’ functions, particularly T cells while inducing regulatory T cells (iTregs). MSCs are very sensitive to inflammatory signals. Their biological functions could remarkably vary after exposure to different pro-inflammatory cytokines, notably TNFα. In this article, we have explored the importance of TNFR2 expression in a series of MSCs’ biological and functional properties. Thus, MSCs from wild-type (WT) and TNFR2 knockout (TNFR2 KO) mice were isolated and underwent several ex vivo experiments to investigate the biological significance of TNFR2 molecule in MSC main functions. Hampering in TNFR2 signaling resulted in reduced MSC colony-forming units and proliferation rate and diminished the expression of all MSC characteristic markers such as stem cell antigen-1 (Sca1), CD90, CD105, CD44, and CD73. TNFR2 KO-MSCs produced more pro-inflammatory cytokines like TNFα, IFNγ, and IL-6 and less anti-inflammatory mediators such as IL-10, TGFβ, and NO and induced Tregs with less suppressive effect. Furthermore, the TNFR2 blockade remarkably decreased MSC regenerative functions such as wound healing, complex tube formation, and endothelial pro-angiogenic support. Therefore, our results reveal the TNFα–TNFR2 axis as a crucial regulator of MSC immunological and regenerative functions.

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3D Culture of Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) Could Improve Bone Regeneration in 3D-Printed Porous Ti6Al4V Scaffolds

Cited by 35 publications

References 40 publications

Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord

Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

TNFR2 Is a Crucial Hub Controlling Mesenchymal Stem Cell Biological and Functional Properties

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