Adipose-derived mesenchymal stem/stromal cells: from the lab bench to the basic concepts for clinical translation

Frontini-López, Yesica Romina; Gojanovich, Aldana Daniela; Masone, Diego; Bustos, Diego Martín; Uhart, Marina

doi:10.32604/biocell.2018.07013

Cited by 8 publications

(5 citation statements)

References 72 publications

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“…The aim of this work was to study the adhesion, viability, proliferation and early stages of osteogenic differentiation capacity of hASCs on nanofibrous matrices composed of poly(ε-caprolactone) (PCL), nanohydroxyapatite (nHA) as bioceramic nanophase and 14-3-3 protein isoform epsilon. This specific protein was recently reported in relation to the development of osteoblasts and related cells [9,10].…”

Section: Introductionmentioning

confidence: 63%

14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity

Rivero

Aldana

López

et al. 2019

J Mater Sci: Mater Med

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Adipose-derived mesenchymal stem cells (ASCs) accelerate the osteointegration of bone grafts and improve the efficiency in the formation of uniform bone tissue, providing a practical and clinically attractive approach in bone tissue regeneration. In this work, the effect of nanofibrous biomimetic matrices composed of poly(ε-caprolactone) (PCL), nanometric hydroxyapatite (nHA) particles and 14-3-3 protein isoform epsilon on the initial stages of human ASCs (hASCs) osteogenic differentiation was investigated. The cells were characterized by flow cytometry and induction to differentiation to adipogenic and osteogenic lineages. The isolated hASCs were induced to differentiate to osteoblasts over all scaffolds, and adhesion and viability of the hASCs were found to be similar. However, the activity of alkaline phosphatase (ALP) as early osteogenic marker in the PCL-nHA/protein scaffold was four times higher than in PCL-nHA and more than five times than the measured in neat PCL.

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Section: Introductionmentioning

confidence: 63%

14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity

Rivero

Aldana

López

et al. 2019

J Mater Sci: Mater Med

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“…hAD-MSCs show a high proliferative potential during in vitro cultivation, are able to self-renew, and can differentiate in vitro as well as in vivo along the osteogenic, adipogenic, myogenic, and chondrogenic lineages. [1,2] Recently, it was also demonstrated the usefulness of hAD-MSCs in the treatment of COVID-19, because of their immunoregulatory capacities. [3][4][5] hAD-MSCs exist within their in vivo niches as part of heterogeneous cell populations, exhibiting variable stemness, differentiation, and immunoregulatory potential.…”

Section: Introductionmentioning

confidence: 99%

Human adipose mesenchymal stromal cells growing into PCL‐nHA electrospun scaffolds undergo hypoxia adaptive ultrastructural changes

Frontini-López

Rivera

Aldana

et al. 2023

Biotechnology Journal

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Human Adipose‐Derived Mesenchymal Stem/Stromal Cells (hAD‐MSCs) have great potential for tissue regeneration. Since transplanted hAD‐MSCs are likely to be placed in a hypoxic environment, culturing the cells under hypoxic conditions might improve their post‐transplantation survival and regenerative performance. The combination of hAD‐MSCs and PCL‐nHA nanofibers synergically improves the contribution of both components for osteoblast differentiation. In this work, we hypothesized that this biomaterial constitutes a hypoxic environment for hAD‐MSCs. We studied the cellular re‐arrangement and the subcellular ultrastructure by Transmission Electron Microscopy (TEM) of hAD‐MSCs grown into PCL‐nHA nanofibers, and we compared them with the same cells grown in two‐dimensional cultures, over tissue culture‐treated plastic, or glass coverslips. Among the most evident changes, PCL‐nHA grown cells showed enlarged mitochondria, and accumulation of glycogen granules, consistent with a hypoxic environment. We observed a 3.5 upregulation (p = 0.0379) of Hypoxia Inducible Factor (HIF)‐1A gene expression in PCL‐nHA grown cells. This work evidences for the first time intra‐cellular changes in three‐dimensional compared to two‐dimensional cultures, which are adaptive responses of the cells to an environment more closely resembling that of the in vivo niche after transplantation, thus PCL‐nHA nanofibers are adequate for hAD‐MSCs pre‐conditioning.

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“…Osteogenesis is the process by which new bone is synthesized [2], however, the available data on osteoblast differentiation is fragmented and incomplete. A major source of discrepancies in this research area is the use of cell lines instead of primary cells [3].…”

Section: Introductionmentioning

confidence: 99%

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage.

López

Gojanovich

Uhart

et al. 2020

Preprint

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Background 14-3-3 protein family binds and regulate hundreds of serine/threonine phosphorylated proteins. Considered as redundant, ubiquitous and constantly expressed, this protein family was treated as an accessory for many signaling systems. Recently, specific biological functions were discovered for each of its seven paralogs in humans. Here, we studied the reversible inhibition by acetylation of its essential N- ε -lysine 49/51 residue during the osteogenic differentiation of human adipose-derived stem cells. Methods Human adipose-derived stem cells were obtained from healthy patients who underwent a dermolipectomy. The material was processed to obtain the ASCs from the stromal vascular fraction. Proteins of interest were analyzed by confocal microscopy and Western blot, and the expression level of selected proteins were modified by using lentivirus and specific shRNAs. Results We found that during the differentiation of ASC, the levels of 14-3-3 acK49/51 increased, showing that inhibition of 14-3-3 is necessary during this process. Among the 7 paralogs of this family, the inhibition by this posttranslational modification occurs mostly on the paralog β , located specifically in the nucleus, where 14-3-3 was described to bind to H3 histone and many transcription factors. Paralog specific inhibition by short hairpin RNA showed that silencing of 14-3-3 β gene, but not 14-3-3γ, increases significantly the osteogenic potential of the cells. Transdifferentiation from osteogenic to adipogenic linage of cell lines that were specifically silenced for 14-3-3 β o γ paralogs showed that 14-3-3b could be a negative regulator of the differentiation to the osteogenic lineage. Conclusion We showed that specifically 14-3-3 β is a negative regulator of osteogenesis. The levels of its inhibition by acetylation on lysine 51 is the key cellular mechanism to regulate it. The HBO1 acetyltransferase could be the enzyme responsible of this modification. Cells were this inhibition was emulated by decreasing the levels of expression of 14-3-3 β showed significant increased potential for the differentiation to the osteogenic lineage.

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Adipose-derived mesenchymal stem/stromal cells: from the lab bench to the basic concepts for clinical translation

Cited by 8 publications

References 72 publications

14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity

14-3-3ε protein-immobilized PCL-HA electrospun scaffolds with enhanced osteogenicity

Human adipose mesenchymal stromal cells growing into PCL‐nHA electrospun scaffolds undergo hypoxia adaptive ultrastructural changes

14-3-3β paralog is inhibited by acetylation during differentiation to the osteogenic lineage.

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