Proangiogenic and Prosurvival Functions of Glucose in Human Mesenchymal Stem Cells upon Transplantation

Deschepper, Mickael; Manassero, Mathieu; Oudina, Karim; Paquet, Joseph; Monfoulet, Laurent-Emmanuel; Bensidhoum, Morad; Logeart-Avramoglou, Delphine; Petite, Hervé

doi:10.1002/stem.1299

Cited by 51 publications

(54 citation statements)

References 25 publications

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“…MSCs are known to survive under near-anoxic condition and may reduce oxygen consumption in the aggregates, altering oxygen distribution. 118 Additionally, MSCs are significant source of endogenous growth factors and the accumulation of these factors in the aggregates is a critical property but remains to be investigated. Thus, quantitative understanding of the temporal and spatial characteristics of MSC aggregates is required for in-depth study of their biological and functional properties.…”

Section: -115mentioning

confidence: 99%

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Sart

Tsai

et al. 2014

Tissue Engineering Part B: Reviews

317

362

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Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications.

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Section: -115mentioning

confidence: 99%

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Sart

Tsai

et al. 2014

Tissue Engineering Part B: Reviews

317

362

View full text Add to dashboard Cite

show abstract

“…To date, the mechanism by which MSCs uptake and use oxygen and nutrients under ischemic conditions remains poorly investigated and understood. Recent studies in sheep , mice , and humans MSCs challenged the pivotal role of oxygen and established that MSCs adapt to near‐anoxia conditions in vitro and increased their in vivo survival rate as long as they have a sufficient glucose (glc) supply . This study aims at further elucidating the mechanisms by which glc and its end‐products are used by hMSCs to fuel their metabolism upon transplantation.…”

Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stem Cell Failure to Adapt to Glucose Shortage and Rapidly Use Intracellular Energy Reserves Through Glycolysis Explains Poor Cell Survival After Implantation

et al. 2018

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Mesenchymal stem cells (MSCs) hold considerable promise in tissue engineering (TE). However, their poor survival when exogenously administered limits their therapeutic potential. Previous studies from our group demonstrated that lack of glucose (glc) (but not of oxygen) is fatal to human MSCs because it serves as a pro-survival and pro-angiogenic molecule for human MSCs (hMSCs) upon transplantation. However, which energy-providing pathways MSCs use to metabolize glc upon transplantation? Are there alternative energetic nutrients to replace glc? And most importantly, do hMSCs possess significant intracellular glc reserves for ensuring their survival upon transplantation? These remain open questions at the forefront of TE based-therapies. In this study, we established for the first time that the in vivo environment experienced by hMSCs is best reflected by near-anoxia (0.1% O ) rather than hypoxia (1%-5% O ) in vitro. Under these near-anoxia conditions, hMSCs rely almost exclusively on glc through anerobic glycolysis for ATP production and are unable to use either exogenous glutamine, serine, or pyruvate as energy substrates. Most importantly, hMSCs are unable to adapt their metabolism to the lack of exogenous glc, possess a very limited internal stock of glc and virtually no ATP reserves. This lack of downregulation of energy turnover as a function of exogenous glc level results in a rapid depletion of hMSC energy reserves that explains their poor survival rate. These new insights prompt for the development of glc-releasing scaffolds to overcome this roadblock plaguing the field of TE based-therapies. Stem Cells 2018;36:363-376.

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“…Several studies described the efficacy of hyperbaric oxygen therapy in improving bone formation [81–84]; however, a study evaluating the effects of hyperbaric oxygen treatment revealed that it did not enhance the preconditioned MSCs with regard to the success of posterolateral lumbar fusion in a validated rabbit model [85]. A more recent study by Deschepper et al [86] showed that glucose also plays a critical role in enhancing the ability of human MSCs to survive in a near-anoxic environment.…”

Section: Resultsmentioning

confidence: 99%

Cellular bone matrices: viable stem cell-containing bone graft substitutes

et al. 2014

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BACKGROUND CONTEXT Advances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used. PURPOSE To critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use. STUDY DESIGN Areview of literature. METHODS A series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products. RESULTS Five different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs’ survival, function, osteoblastic potential, and cytokine production once implanted into the intended host. CONCLUSIONS Cellular bone matrices may be a promising bone augmentation technology in spinal fusion surgery. Although CBMs appear to be safe for use as bone graft substitutes, their efficacy in spinal fusion surgery remains highly inconclusive. Large, nonindustry sponsored studies evaluating the efficacy of CBMs are required. Without results from such studies, surgeons must be made aware of the potential pitfalls of CBMs in spinal fusion surgery. With the currently available data, there is insufficient evidence to support the use of CBMs as bone graft substitutes in spinal fusion surgery.

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Proangiogenic and Prosurvival Functions of Glucose in Human Mesenchymal Stem Cells upon Transplantation

Cited by 51 publications

References 25 publications

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Human Mesenchymal Stem Cell Failure to Adapt to Glucose Shortage and Rapidly Use Intracellular Energy Reserves Through Glycolysis Explains Poor Cell Survival After Implantation

Cellular bone matrices: viable stem cell-containing bone graft substitutes

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