Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells

Klontzas, Michail E.; Kenanidis, Eustathios; Heliotis, Manolis; Tsiridis, Eleftherios; Mantalaris, Athanasios

doi:10.1517/14712598.2015.1068755

Cited by 48 publications

(36 citation statements)

References 75 publications

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“…MSCs isolated from various sources have been investigated for their osteogenic potential. MSCs derived from fetal tissues, such as umbilical cord matrix, amniotic fluid, and umbilical cord blood (UCB) have emerged as an attractive alternative to adult MSCs, because of their higher proliferation potential, lack of donor site morbidity, and the possibility of their off-the-shelf use for the production of personalized autologous bone grafts [3,4]. …”

Section: Introductionmentioning

confidence: 99%

Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents

Klontzas

Vernardis

Heliotis

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs (UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue regeneration because of their higher proliferation potential, lack of donor site morbidity, and their off-the-shelf potential. MSCs differentiated toward the osteogenic lineage exhibit a specific metabolic phenotype characterized by reliance to oxidative phosphorylation for energy production and reduced glycolytic rates. Currently, limited information exists on the metabolic transitions at different stages of the osteogenic process after osteoinduction with different agents. Herein, the osteoinduction efficiency of BMP-2 and dexamethasone on UCB MSCs was assessed using gas chromatography–mass spectrometry (GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21 days of induction. Whereas both agents when administered individually were able to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less effective than dexamethasone in promoting alkaline phosphatase expression. The metabolomics analysis revealed that each agent induced distinct metabolic alterations, including changes in amino acid pools, glutaminolysis, one-carbon metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to primary osteoblasts when induced with dexamethasone but not with BMP-2, highlighting the fact that metabolomics analysis is sensitive enough to reveal potential differences in the osteogenic efficiency and can be used as a quality control assay for evaluating the osteogenic process.

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Section: Introductionmentioning

confidence: 99%

Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents

Klontzas

Vernardis

Heliotis

et al. 2017

Stem Cells and Development

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“…Besides adult BM‐MSCs, neonatal cord blood USSCs and CB‐MSCs are attractive cell sources for bone‐regenerative approaches in vivo (Handschel et al , ; Klontzas et al , ; Langenbach et al , ). Like the ‘gold standard’ BM‐MSCs, neonatal cord blood‐derived USSCs and CB‐MSCs can be differentiated in vitro into the chondrogenic and osteogenic lineages, while showing a more immature osteogenic signature in comparison to adult BM‐MSCs (Bosch et al , ).…”

Section: Introductionmentioning

confidence: 99%

Low oxygen tension reveals distinctHOXcodes in human cord blood-derived stromal cells associated with specific endochondral ossification capacitiesin vitroandin vivo

Liedtke

Sacchetti

Laitinen

et al. 2016

J Tissue Eng Regen Med

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Effects of oxygen tension on the generation, expansion, proliferation and differentiation of stromal cell types is widely described in the literature. However, data on the internal heterogeneity of applied cell populations at different O levels and possible impacts on differentiation potentials are controversial. Here, the expression of 39 human HOX genes was determined in neonatal cord blood stromal cells and linked to differentiation-associated signatures. In cord blood, unrestricted somatic stromal cells (USSCs), lacking HOX gene expression, and cord blood-derived multipotent stromal cells (CB-MSCs), expressing about 20 HOX genes, are distinguished by their specific HOX code. Interestingly, 74% of the clones generated at 21% O were HOX-negative USSCs, whereas 73% of upcoming clones at 3% O were HOX-positive CB-MSCs. In order to better categorize distinct cell lines generated at 3% O , the expression of all 39 HOX genes within HOX clusters A, B, C and D were tested and new subtypes defined: cells negative in all four HOX clusters (USSCs); cells positive in all four clusters (CB-MSCs ); and subpopulations missing a single cluster (CB-MSCs and CB-MSCs ). Comprehensive qPCR analyses of established chondro-osteomarkers revealed subtype-specific signatures verifiably associated with in vitro and in vivo differentiation capacity. The data presented here underline the necessity of better characterizing distinct cell populations at a clonal level, taking advantage of the inherent specific HOX code as a distinguishing feature between individual subtypes. Moreover, the correlation of subtype-specific molecular signatures with in vitro and in vivo bone formation is discussed. Copyright © 2016 John Wiley & Sons, Ltd.

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“…9 Therefore, it is believed that hUCMSCs own the characteristics of both seed cells and cytokines in the process of fabrication of tissue-engineered bone, which will be a promising choice to enhance the bioactivity of tissue-engineered bone graft. 10 Numerous researches have also shown that hUCMSCs have superior osteogenic properties attached to the scaffolds and are suitable seed cells for bone tissue engineering. 11 Given that some studies hold the osteogenic ability of hUCMSCs is weaker than that of hBMSCs, it is worthy to improve the osteogenesis ability of hUCMSCs.…”

Section: Introductionmentioning

confidence: 99%

A novel method to improve the osteogenesis capacity of hUCMSCs with dual‐directional pre‐induction under screened co‐culture conditions

Rong

Zhou

et al. 2019

Cell Proliferation

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Objectives Mesenchymal stem cells (MSCs) based therapy for bone regeneration has been regarded as a promising method in the clinic. However, hBMSCs with invasive harvesting process and undesirable proliferation rate hinder the extensive usage. HUCMSCs of easier access and excellent performances provide an alternative for the fabrication of tissue‐engineered bone construct. Evidence suggested the osteogenesis ability of hUCMSCs was weaker than that of hBMSCs. To address this issue, a co‐culture strategy of osteogenically and angiogenically induced hUCMSCs has been proposed since thorough vascularization facilitates the blood‐borne nutrition and oxygen to transport in the scaffold, synergistically expediting the process of ossification. Materials and methods Herein, we used osteogenic‐ and angiogenic‐differentiated hUCMSCs for co‐culture in screened culture medium to elevate the osteogenic capacity with in vitro studies and finally coupled with 3D TCP scaffold to repair rat's critical‐sized calvarial bone defect. By dual‐directional induction, hUCMSCs could differentiate into osteoblasts and endothelial cells, respectively. To optimize the co‐culture condition, gradient ratios of dual‐directional differentiated hUCMSCs co‐cultured under different medium were studied to determine the appropriate condition. Results It revealed that the osteogenic‐ and angiogenic‐induced hUCMSCs mixed with the ratio of 3:1 co‐cultured in the mixed medium of osteogenic induction medium to endothelial cell induction medium of 3:1 possessed more mineralization nodules. Similarly, ALP and osteogenesis/angiogenesis‐related genes expressions were relatively higher. Further evidence of bone defect repair with 3D printed TCP of 3:1 group exhibited better restoration outcomes. Conclusions Our work demonstrated a favourable and convenient approach of dual‐directional differentiated hUCMSCs co‐culture to improve the osteogenesis, establishing a novel way to fabricate tissue‐engineered bone graft with 3D TCP for large bone defect augmentation.

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Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells

Cited by 48 publications

References 75 publications

Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents

Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents

Low oxygen tension reveals distinctHOXcodes in human cord blood-derived stromal cells associated with specific endochondral ossification capacitiesin vitroandin vivo

A novel method to improve the osteogenesis capacity of hUCMSCs with dual‐directional pre‐induction under screened co‐culture conditions

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