Single cell-derived clones from human adipose stem cells present different immunomodulatory properties

Sempere, J.; Martínez-Peinado, Pascual; Arribas, María I.; Reig, Juan A.; Şen, Mesut; Zubcoff, José; Fraga, Mario F.; Fernández, Agustín F.; Santana, Alfredo; Roche, Enrique

doi:10.1111/cei.12270

Cited by 21 publications

(19 citation statements)

References 46 publications

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“…Also, continuous culture in either FCS or hPL affected the distribution of ASCs within the subcategories of CD146 + and/or CD271 + cells. Whether and how this altered expression of the classic stem cell markers CD73 and CD105 reflects on the functionality of the ASCs is still uncertain, but CD73 has been suggested to be involved in differentiation [62] and regulation of the immune modulatory pathway together with CD105 [63, 64].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells

Porsborg

Nielsen

Pennisi

et al. 2016

Stem Cells Translational Medicine

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Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet lysate (hPL), and a fully defined medium on the initiation and maintenance of ASC cultures. ASCs obtained from five donors were cultured in five different media: StemPro, Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% hPL, or α-minimum essential medium (A-MEM) supplemented with 5% hPL, 10% hPL, or 10% FCS. The effect of media on proliferation, colony-forming units (CFUs), attachment, and morphology was assessed along with cell size, granularity, and immunophenotype. StemPro greatly compromised the initiation of ASC cultures, which could not survive more than a few passages. Cells cultured in A-MEM proliferated at a faster rate than in DMEM, and hPL significantly enhanced cell size, granularity, and proliferation compared with FCS. All media except StemPro supported CFUs equally well. Analysis of surface markers revealed higher levels of CD73 and CD105 in FCS-cultured ASCs, whereas increased levels of CD146 were found in hPL-cultured cells. Multiparametric flow cytometric analysis performed after seven passages revealed the existence of four distinct ASC subpopulations, all positive for CD73, CD90, and CD105, which mainly differed by their expression of CD146 and CD271. Analysis of the different subpopulations might represent an important biological measure when assessing different medium formulations for a particular clinical application.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells

Porsborg

Nielsen

Pennisi

et al. 2016

Stem Cells Translational Medicine

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“…Sempere et al examined human MSCs: the group showed results that provided mechanisms that may be involved with the in vivo MSC-mediated induction of tolerance, which to their point of view could be used therapeutically for reducing graft rejection [41]. Xie et al found that anti-inflammatory proteins, which are induced from xenografted hASCs, are capable of responding to host inflammatory signals [42].…”

Section: Immunogenicitymentioning

confidence: 99%

Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit

Kappos

Engels

Tremp

et al. 2015

Stem Cells and Development

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Tissue engineering is a popular topic in peripheral nerve repair. Combining a nerve conduit with supporting adipose-derived cells could offer an opportunity to prevent time-consuming Schwann cell culture or the use of an autograft with its donor site morbidity and eventually improve clinical outcome. The aim of this study was to provide a broad overview over promising transplantable cells under equal experimental conditions over a long-term period. A 10-mm gap in the sciatic nerve of female Sprague-Dawley rats (7 groups of 7 animals, 8 weeks old) was bridged through a biodegradable fibrin conduit filled with rat adipose-derived stem cells (rASCs), differentiated rASCs (drASCs), human (h)ASCs from the superficial and deep abdominal layer, human stromal vascular fraction (SVF), or rat Schwann cells, respectively. As a control, we resutured a nerve segment as an autograft. Long-term evaluation was carried out after 12 weeks comprising walking track, morphometric, and MRI analyses. The sciatic functional index was calculated. Cross sections of the nerve, proximal, distal, and in between the two sutures, were analyzed for re-/myelination and axon count. Gastrocnemius muscle weights were compared. MRI proved biodegradation of the conduit. Differentiated rat ASCs performed significantly better than undifferentiated rASCs with less muscle atrophy and superior functional results. Superficial hASCs supported regeneration better than deep hASCs, in line with published in vitro data. The best regeneration potential was achieved by the drASC group when compared with other adipose tissue-derived cells. Considering the ease of procedure from harvesting to transplanting, we conclude that comparison of promising cells for nerve regeneration revealed that particularly differentiated ASCs could be a clinically translatable route toward new methods to enhance peripheral nerve repair.

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“…Recent advances in the ability to study single-cell transcriptomes can be leveraged to better understand the cellular composition of adipose tissue [11][12][13]. Single-cell transcriptomics of nonmature adipocytes in mouse fat has revealed specific populations of adipocyte stem cells primed to expand in response to adrenergic stimulation [13], stromal cells capable of inhibiting adipogenesis [11], and cells with enhanced adipogenic or fibro-inflammatory properties [14]. The use of single-cell transcriptomics to define mature adipocyte subtypes is complicated by the large size and high buoyancy of these cells, and the fact that the extensive proteolytic digestion required to isolate them from the adipose tissue compromises their viability and alters their phenotype [15].…”

Section: Introductionmentioning

confidence: 99%

“Multiple human adipocyte subtypes and mechanisms of their development”

Desai

Yang

et al. 2019

Preprint

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Human adipose tissue depots perform numerous diverse physiological functions, and are differentially linked to metabolic disease risk, yet only two major human adipocyte subtypes have been described, white and "brown/brite/beige." The diversity and lineages of adipocyte classes have been studied in mice using genetic methods that cannot be applied in humans. Here we circumvent this problem by studying the fate of single mesenchymal progenitor cells obtained from human adipose tissue. We report that a minimum of four human adipocyte subtypes can be distinguished by transcriptomic analysis, specialized for functionally distinct processes such as adipokine secretion and thermogenesis. Evidence for the presence of these adipocytes subtypes in adult humans is evidenced by differential expression of key adipokines leptin and adiponectin in isolated mature adipocytes. The human adipocytes most similar to the mouse "brite/beige" adipocytes are enriched in mechanisms that promote iron accumulation and protect from oxidative stress, and are derived from progenitors that express high levels of cytokines such as IL1B, IL8, IL11 and the IL6 family cytokine LIF, and low levels of the transcriptional repressors ID1 and ID3. Our finding of this adipocyte repertoire and its developmental mechanisms provides a high-resolution framework to analyze human adipose tissue architecture and its role in systemic metabolism and metabolic disease.

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Single cell-derived clones from human adipose stem cells present different immunomodulatory properties

Cited by 21 publications

References 46 publications

Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells

Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells

Peripheral Nerve Repair: Multimodal Comparison of the Long-Term Regenerative Potential of Adipose Tissue-Derived Cells in a Biodegradable Conduit

“Multiple human adipocyte subtypes and mechanisms of their development”

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