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      Highly Pluripotent Adipose-Derived Stem Cell–Enriched Nanofat: A Novel Translational System in Stem Cell Therapy

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          Abstract

          Fat graft is widely used in plastic and reconstructive surgery. The size of the injectable product, the unpredictable fat resorption rates, and subsequent adverse effects make it tricky to inject untreated fat into the dermal layer. Mechanical emulsification of fat tissue, which Tonnard introduced, solves these problems, and the product obtained was called nanofat. Nanofat is widely used in clinical and aesthetic settings to treat facial compartments, hypertrophic and atrophic scars, wrinkle attenuation, skin rejuvenation, and alopecia. Several studies demonstrate that the tissue regeneration effects of nanofat are attributable to its rich content of adipose-derived stem cells. This study aimed to characterize Hy-Tissue Nanofat product by investigating morphology, cellular yield, adipose-derived stem cell (ASC) proliferation rate and clonogenic capability, immunophenotyping, and differential potential. The percentage of SEEA3 and CD105 expression was also analyzed to establish the presence of multilineage-differentiating stress-enduring (MUSE) cell. Our results showed that the Hy-Tissue Nanofat kit could isolate 3.74 × 10 4 ± 1.31 × 10 4 proliferative nucleated cells for milliliter of the treated fat. Nanofat-derived ASC can grow in colonies and show high differentiation capacity into adipocytes, osteocytes, and chondrocytes. Moreover, immunophenotyping analysis revealed the expression of MUSE cell antigen, making this nanofat enriched of pluripotent stem cell, increasing its potential in regenerative medicine. The unique characteristics of MUSE cells give a simple, feasible strategy for treating a variety of diseases.

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          Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations

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            Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control.

            Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified, which constrains them to act as short-range cellular signals. The locality of Wnt signaling dictates that stem cells exiting the Wnt signaling domain differentiate, spatially delimiting the niche in certain tissues. In some instances, stem cells may act as or generate their own niche, enabling the self-organization of patterned tissues. In this Review, we discuss the various ways by which Wnt operates in stem cell control and, in doing so, identify an integral program for tissue renewal and regeneration.
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              Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation

              Adipose/fat tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration and can also give rise to a substantial number of cultured, multipotent adipose-derived stromal cells (ADSCs). Recently, both SVF and ADSCs have gained wide-ranging translational significance in regenerative medicine. Initially used for cosmetic breast enhancement, this mode of treatment has found use in many diseases involving immune disorders, tissue degeneration, and ischaemic conditions. In this review, we try to address several important aspects of this field, outlining the biology, technology, translation, and challenges related to SVF- and ADSC-based therapies. Starting from the basics of SVF and ADSC isolation, we touch upon recently developed technologies, addressing elements of novel methods and devices under development for point-of-care isolation of SVF. Characterisation of SVF cells and ADSCs is also an evolving area and we look into unusual expression of CD34 antigen as an interesting marker for such purposes. Based on reports involving different cells of the SVF, we draw a potential mode of action, focussing on angiogenesis since it involves multiple cells, unlike immunomodulation which is governed predominantly by ADSCs. We have looked into the latest research, experimental therapies, and clinical trials which are utilising SVF/ADSCs in conditions such as multiple sclerosis, Crohn’s disease, peripheral neuropathy, osteoarthritis, diabetic foot ulcer, and so forth. However, problems have arisen with regards to the lack of proper regulatory guidelines for such therapies and, since the introduction of US Food and Drug Administration draft guidelines and the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act, the debate became more public with regards to safe and efficacious use of these cells.
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                Author and article information

                Journal
                Cell Transplant
                Cell Transplant
                CLL
                spcll
                Cell Transplantation
                SAGE Publications (Sage CA: Los Angeles, CA )
                0963-6897
                1555-3892
                27 May 2023
                Jan-Dec 2023
                : 32
                : 09636897231175968
                Affiliations
                [1 ] Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine, and Movement, University of Verona, Verona, Italy
                [2 ] Safety Assessment Department, Aptuit (Verona) S.r.l., an Evotec Company, Verona, Italy
                [3 ] Department of Medical Area (DAME), Clinic of Plastic and Reconstructive Surgery, Academic Hospital of Udine, University of Udine, Udine, Italy
                [4 ] Research and Training Center in Regenerative Surgery, Accademia del Lipofilling, Montelabbate, Italy
                [5 ] Department of General and Specialties Surgery, SOD of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy
                Author notes
                [*]Francesco De Francesco, Department of General and Specialties Surgery, SOD of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Via Conca 71, 60126 Ancona, Italy. Email: francesco.defrancesco@ 123456ospedaliriuniti.marche.it
                [*]Michele Riccio, Department of General and Specialties Surgery, SOD of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, Via Conca 71, 60126 Ancona, Italy. Email: michele.riccio@ 123456ospedaliriuniti.marche.it
                [*]

                The authors contributed equally to the work

                [†]

                Equally corresponding authors.

                Author information
                https://orcid.org/0000-0001-7336-0099
                https://orcid.org/0000-0003-2977-7828
                Article
                10.1177_09636897231175968
                10.1177/09636897231175968
                10226300
                37243545
                58719193-5aa6-4a35-9899-61e2cf7c7721
                © The Author(s) 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 23 November 2022
                : 25 April 2023
                : 29 April 2023
                Categories
                Original Article
                Custom metadata
                January-December 2023
                ts1

                nanofat,stromal vascular fraction,adipose stem cells,stem cell therapy,mechanical disaggregation,translational therapy

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