Epidural fat mesenchymal stem cells: Important microenvironmental regulators in health, disease, and regeneration

Shah, Sophia; Mudigonda, Sathvika; Mitha, Alim P.; Salo, Paul; Krawetz, Roman

doi:10.1002/bies.202000215

Cited by 4 publications

(6 citation statements)

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“…However, several difficulties have been observed in conducting basic studies with EF-MSCs. To date, EVs have been considered as novel source materials for regenerative studies and clinical relevance [3,[7][8][9]29]. EVs exhibit several advantages for such research, and one of their advantages over MSCs is that they do not consume their donor tissues or cells.…”

Section: Discussionmentioning

confidence: 99%

“…To date, only a basic study has indicated that EF contains mesenchymal stem cells (MSCs) [ 1 , 2 ]. A few studies have shown that MSCs derived from EF can produce an affirmative effect for specific pathologies in the spine, such as spinal cord injury and post-lumbar surgery syndrome [ 2 , 3 ]. However, spine physicians are ill-informed on EF.…”

Section: Introductionmentioning

confidence: 99%

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Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

et al. 2022

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An experimental study with extracellular vesicles (EVs) from mesenchymal stem cell (MSC) of the epidural fat (EF) of the spine. Purpose: This study aims to isolate the exosomes from epidural fat-derived mesenchymal stem cells (EF-MSCs) and fully characterize the EF-MSC-EVs. Overview of Literature: EF-MSCs were reported in 2019, and a few studies have shown the positive outcomes of using EF-MSCs to treat specific spine pathologies. However, MSCs have significant limitations for conducting basic studies or developing therapeutic agents. Although EVs are an emerging research topic, no studies have focused on EVs, especially exosomes, from EF and EF-MSCs. Methods: In this study, we isolated the exosomes using the tangential flow filtration (TFF) system with exosome-depleted fetal bovine serum and performed the characterization tests via western blotting, reverse transcription-polymerase chain reaction, nanoparticle tracking analysis (NTA), and transmission electron microscopy. Results: In transmission electron microscopy, the exosome had a diameter of approximately 100-200 nm and had a spherical shape, whereas in the NTA, the exosome had an average diameter of 142.8 nm with a concentration of 1.27×10 10 particles/mL. The flow cytometry analysis showed the expression of CD63 and CD81. The western blotting analysis showed the positive markers. Conclusions: These findings showed that isolating the exosomes via TFF resulted in high-quality EF-MSC exosome yield. Further studies with exosomes from EF-MSC are needed to evaluate the function and role of the EF tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

et al. 2022

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“…[ 40 ] Therefore, it is not uncommon for this tissue to be discarded during surgical procedures. [ 28 ] However, there is a growing body of evidence suggesting that epidural fat is necessary to maintain the dural microenvironment and that the absence of epidural fat can lead to worse post‐operative outcomes. [ 41 ] Recognizing its importance, studies using adipose‐derived MPCs within scaffolds and matrices have attempted to reconstruct epidural fat and have showed reduced adherence of fibrotic tissue to the dura mater when used in injury models.…”

Section: Discussionmentioning

confidence: 99%

“…We have also used this mouse to determine that MPCs in the epidural fat and dura express Prx1. [13,15,28,29] We further employed this lineage tracking method on a p21 −/− background to identify if there was a change in behavior of these MPCs in vivo with the deletion of p21.…”

Section: Introductionmentioning

confidence: 99%

Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs

et al. 2022

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during revision surgeries for patients with epidural fibrosis. [2] Patients who experience incidental durotomies suffer from worse post-operative clinical results, such as a higher rate of reoperations, increased back pain, and reduced working ability. [3] However, appropriate treatment can diminish long-term sequelae post-dural injury. The use of synthetic and biological grafts to treat insults to the dura mater began in the 20th century, including polymer sheets, autografts, allografts, and even xenografts. [4] To date however, a successful graft which mimics perfectly the collagen fiber arrangement and accordingly the biomechanical properties of the dura mater remains elusive.Given loss of epidural fat can promote fibrosis in the vertebral environment, efforts have been made to re-introduce epidural fat into the vertebral column including engineered fat from adiposederived mesenchymal progenitor cells (MPCs), [1] injectable extracellular matrices, [5][6][7] and fat grafting. [6,[8][9][10] Attempts at preventing epidural fibrosis thus protecting the dura mater have also been made using biomaterials like DuraGen, [11] and injection of nonsteroidal anti-inflammatory drugs to re-balance the microenvironment to promote healing. [12] Regardless of the multiple different techniques being explored, no treatment exists that has gained wide clinical acceptance to prevent epidural fibrosis. Epidural fat contains a population of mesenchymal progenitor cells (MPCs), and this study explores the behavior of these cells on the adjacent dura mater during growth and in response toinjury in a p21 knockout mouse model. p21 −/− mice are known to have increased cell proliferation and enhanced tissue regeneration post-injury. Therefore, it is hypothesized that the process by which epidural fat MPCs maintain the dura mater can be accelerated in p21 −/− mice. Using a Prx1 lineage tracing mouse model, the epidural fat MPCs are found to increase in the dura mater over time in both C57BL/6 (p21 +/+ ) and p21 −/− mice; however, by 3 weeks post-tamoxifen induction, few MPCs are observed in p21 −/− mice. These endogenous MPCs also localize to dural injuries in both mouse strains, with MPCs in p21 −/− mice demonstrating increased proliferation. When epidural fat MPCs derived from p21 −/− mice are transplanted into dural injuries in C57BL/6 mice, these MPCs are found in the injury site. It is demonstrated that epidural fat MPCs play a role in dural tissue maintenance and are able to directly contribute to dural injury repair. This suggests that these MPCs have the potential to treat injuries and/or pathologies in tissues surrounding the spinal cord.

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“…Recently, the need for research on the characteristics and functions of epidural fat tissue has emerged. Studies have reported that MSCs can also be isolated from epidural fat tissue, and that the isolated MSCs exhibited therapeutic effects [11,16,21,40,41]. However, the specific characteristics and functions of human epidural fat MSCs and human epidural fat MSC-derived EVs are not yet clear.…”

Section: Discussionmentioning

confidence: 99%

Comparisons of Extracellular Vesicles from Human Epidural Fat-Derived Mesenchymal Stem Cells and Fibroblast Cells

Sung

Kang

Choi

et al. 2021

IJMS

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Extracellular vesicles (EVs) are generated and secreted by cells into the circulatory system. Stem cell-derived EVs have a therapeutic effect similar to that of stem cells and are considered an alternative method for cell therapy. Accordingly, research on the characteristics of EVs is emerging. EVs were isolated from human epidural fat-derived mesenchymal stem cells (MSCs) and human fibroblast culture media by ultracentrifugation. The characterization of EVs involved the typical evaluation of cluster of differentiation (CD antigens) marker expression by fluorescence-activated cell sorting, size analysis with dynamic laser scattering, and morphology analysis with transmission electron microscopy. Lastly, the secreted levels of cytokines and chemokines in EVs were determined by a cytokine assay. The isolated EVs had a typical size of approximately 30–200 nm, and the surface proteins CD9 and CD81 were expressed on human epidural fat MSCs and human fibroblast cells. The secreted levels of cytokines and chemokines were compared between human epidural fat MSC-derived EVs and human fibroblast-derived EVs. Human epidural fat MSC-derived EVs showed anti-inflammatory effects and promoted macrophage polarization. In this study, we demonstrated for the first time that human epidural fat MSC-derived EVs exhibit inflammatory suppressive potency relative to human fibroblast-derived EVs, which may be useful for the treatment of inflammation-related diseases.

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Epidural fat mesenchymal stem cells: Important microenvironmental regulators in health, disease, and regeneration

Cited by 4 publications

References 78 publications

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs

Comparisons of Extracellular Vesicles from Human Epidural Fat-Derived Mesenchymal Stem Cells and Fibroblast Cells

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Epidural fat mesenchymal stem cells: Important microenvironmental regulators in health, disease, and regeneration

Cited by 4 publications

References 78 publications

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine

Prx1+ MPCs Accumulate in the Dura Mater of Wild‐Type and p21−/− Mice Followed by a Specific Reduction in p21−/− Dural MPCs

Comparisons of Extracellular Vesicles from Human Epidural Fat-Derived Mesenchymal Stem Cells and Fibroblast Cells

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Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs