Long-term in vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue: proteomic signature and cellular content

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

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Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells

Blood ◽

10.1182/blood-2009-05-219923 ◽

2010 ◽

Vol 115 (5) ◽

pp. 957-964 ◽

Cited By ~ 119

Author(s):

Jinah Han ◽

Young Jun Koh ◽

Hye Rin Moon ◽

Hyun Gee Ryoo ◽

Chung-Hyun Cho ◽

...

Keyword(s):

Adipose Tissue ◽

Progenitor Cells ◽

High Efficiency ◽

Stromal Vascular Fraction ◽

Hematopoietic Stem ◽

Blood Transplantation ◽

Variable Extent ◽

Stem And Progenitor Cells

Abstract The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin−Sca-1+c-kit+ (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 × 105 freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a long-term (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte–colony-stimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs.

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Generation of a Novel Transgenic Zebrafish for Studying Adipocyte Development and Metabolic Control

International Journal of Molecular Sciences ◽

10.3390/ijms22083994 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3994

Author(s):

Yousheng Mao ◽

Kwang-Heum Hong ◽

Weifang Liao ◽

Li Li ◽

Seong-Jin Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Metabolic Diseases ◽

Fluorescent Protein ◽

Therapeutic Interventions ◽

Transgenic Zebrafish ◽

Zebrafish Model ◽

Adipose Tissues ◽

Green Fluorescent

Zebrafish have become a popular animal model for studying various biological processes and human diseases. The metabolic pathways and players conserved among zebrafish and mammals facilitate the use of zebrafish to understand the pathological mechanisms underlying various metabolic disorders in humans. Adipocytes play an important role in metabolic homeostasis, and zebrafish adipocytes have been characterized. However, a versatile and reliable zebrafish model for long-term monitoring of adipose tissues has not been reported. In this study, we generated stable transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) in adipocytes. The transgenic zebrafish harbored adipose tissues that could be detected using GFP fluorescence and the morphology of single adipocyte could be investigated in vivo. In addition, we demonstrated the applicability of this model to the long-term in vivo imaging of adipose tissue development and regulation based on nutrition. The transgenic zebrafish established in this study may serve as an excellent tool to advance the characterization of white adipose tissue in zebrafish, thereby aiding the development of therapeutic interventions to treat metabolic diseases in humans.

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Preliminary evaluations of 3-dimensional human skin models for their ability to facilitate in vitro the long-term development of the debilitating obligatory human parasite Onchocerca volvulus

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008503 ◽

2020 ◽

Vol 14 (11) ◽

pp. e0008503

Author(s):

Christoph Malkmus ◽

Shabnam Jawahar ◽

Nancy Tricoche ◽

Sara Lustigman ◽

Jan Hansmann

Keyword(s):

Adipose Tissue ◽

Developmental Stages ◽

Onchocerca Volvulus ◽

River Blindness ◽

Mature Adult ◽

3 Dimensional ◽

Human Parasite

Onchocerciasis also known as river blindness is a neglected tropical disease and the world's second-leading infectious cause of blindness in humans; it is caused by Onchocerca volvulus. Current treatment with ivermectin targets microfilariae and transmission and does not kill the adult parasites, which reside within subcutaneous nodules. To support the development of macrofilaricidal drugs that target the adult worm to further support the elimination of onchocerciasis, an in-depth understanding of O. volvulus biology especially the factors that support the longevity of these worms in the human host (>10 years) is required. However, research is hampered by a lack of access to adult worms. O. volvulus is an obligatory human parasite and no small animal models that can propagate this parasite were successfully developed. The current optimized 2-dimensional (2-D) in vitro culturing method starting with O. volvulus infective larvae does not yet support the development of mature adult worms. To overcome these limitations, we have developed and applied 3-dimensional (3-D) culture systems with O. volvulus larvae that simulate the human in vivo niche using in vitro engineered skin and adipose tissue. Our proof of concept studies have shown that an optimized indirect co-culture of in vitro skin tissue supported a significant increase in growth of the fourth-stage larvae to the pre-adult stage with a median length of 816–831 μm as compared to 767 μm of 2-D cultured larvae. Notably, when larvae were co-cultured directly with adipose tissue models, a significant improvement for larval motility and thus fitness was observed; 95% compared to 26% in the 2-D system. These promising co-culture concepts are a first step to further optimize the culturing conditions and improve the long-term development of adult worms in vitro. Ultimately, it could provide the filarial research community with a valuable source of O. volvulus worms at various developmental stages, which may accelerate innovative unsolved biomedical inquiries into the parasite’s biology.

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Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention

Journal of Tissue Engineering ◽

10.1177/2041731417735402 ◽

2017 ◽

Vol 8 ◽

pp. 204173141773540 ◽

Cited By ~ 5

Author(s):

Arta Kelmendi-Doko ◽

J Peter Rubin ◽

Katarina Klett ◽

Christopher Mahoney ◽

Sheri Wang ◽

...

Keyword(s):

Drug Delivery ◽

Adipose Tissue ◽

Glycolic Acid ◽

In Vitro Release ◽

Controlled Delivery ◽

Release Time ◽

Control Group ◽

Volume Retention

Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for 6 months. The hypothesis that the continued release of dexamethasone from polymeric microspheres would enhance both adipogenesis and angiogenesis more significantly when compared to the single-walled microsphere model, resulting in long-term adipose volume retention, was tested. Dexamethasone was encapsulated within single-walled poly(lactic- co-glycolic acid) microspheres (Dex SW MS) and compared to dexamethasone encapsulated in a poly(lactic- co-glycolic acid) core surrounded by a shell of poly-l-lactide. The double-walled polymer microsphere system in the second model was developed to create a more sustainable drug delivery process. Dexamethasone-loaded poly(lactic- co-glycolic acid) microspheres (Dex SW MS) and dexamethasone-loaded poly(lactic- co-glycolic acid)/poly-l-lactide double-walled microspheres (Dex DW MS) were prepared using single and double emulsion/solvent techniques. In vitro release kinetics were determined. Two doses of each type of microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with 0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate-only controls were examined. Samples were analyzed grossly and histologically after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere-containing samples demonstrated greater adipose tissue retention compared to the control group. Histological analysis, including hematoxylin and eosin and CD31 staining, indicated increased vascularization (p < 0.05) within the Dex MS-containing samples. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly affects adipose tissue retention by maintaining healthy tissue formation and vascularization. Dex DW MS provide an improved model to former Dex SW MS, resulting in notably longer release time and, consequently, larger volumes of adipose retained in vivo. The use of microspheres, specifically double-walled, as vehicles for controlled drug delivery of adipogenic factors therefore present a clinically relevant model of adipose retention that has the potential to greatly improve soft tissue repair.

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Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00473.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. E600-E612 ◽

Cited By ~ 1

Author(s):

Zach Carlson ◽

Hannah Hafner ◽

Molly Mulcahy ◽

Kaylie Bullock ◽

Allen Zhu ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Secretion ◽

Beta Cell ◽

Glucose Homeostasis ◽

White Adipose Tissue ◽

Female Offspring ◽

Immunofluorescent Staining ◽

Beta Cell Proliferation

We previously demonstrated that exposing mouse dams to metformin during gestation results in increased beta-cell mass at birth and increased beta-cell insulin secretion in adult male offspring. Given these favorable changes after a gestational maternal metformin exposure, we wanted to understand the long-term metabolic impact on offspring after exposing dams to metformin during the postnatal window. The newborn period provides a feasible clinical window for intervention and is important for beta-cell proliferation and metabolic tissue development. Using a C57BL/6 model, we administered metformin to dams from the day of birth to postnatal day 21. We monitored maternal health and offspring growth during the lactation window, as well as adult glucose homeostasis through in vivo testing. At necropsy we assessed pancreas and adipocyte morphology using histological and immunofluorescent staining techniques. We found that metformin exposure programmed male and female offspring to be leaner with a higher proportion of small adipocytes in the gonadal white adipose tissue (GWAT). Male, but not female, offspring had an improvement in glucose tolerance as young adults concordant with a mild increase in insulin secretion in response to glucose in vivo. These data demonstrate long-term metabolic programming of offspring associated with maternal exposure to metformin during lactation.

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In Vivo Development and Long-Term Survival of Engineered Adipose Tissue Depend on In Vitro Precultivation Strategy

Tissue Engineering Part A ◽

10.1089/tea.2007.0130 ◽

2008 ◽

Vol 14 (2) ◽

pp. 275-284 ◽

Cited By ~ 36

Author(s):

Barbara Weiser ◽

Lukas Prantl ◽

Thomas E.O. Schubert ◽

Johannes Zellner ◽

Claudia Fischbach-Teschl ◽

...

Keyword(s):

Adipose Tissue ◽

Term Survival ◽

Long Term Survival

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Long-Lasting Anti-Inflammatory Activity of Human Microfragmented Adipose Tissue

Stem Cells International ◽

10.1155/2019/5901479 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Sara Nava ◽

Valeria Sordi ◽

Luisa Pascucci ◽

Carlo Tremolada ◽

Emilio Ciusani ◽

...

Keyword(s):

Adipose Tissue ◽

Inflammatory Activity ◽

Tissue Cell ◽

Single Shot ◽

Term Survival ◽

Long Term Survival ◽

Anti Inflammatory

Over the last few years, human microfragmented adipose tissue (MFAT), containing significant levels of mesenchymal stromal cells (MSCs) and obtained from fat lipoaspirate (LP) through a minimal manipulation in a closed system device, has been successfully used in aesthetic medicine as well as in orthopedic and general surgery. Interestingly, in orthopedic diseases, this ready-to-use adipose tissue cell derivative seems to have a prolonged time efficacy even upon a single shot injection into osteoarthritic tissues. Here, we investigated the long-term survival and content of MSCs as well the anti-inflammatory activity of LP and its derived MFAT in vitro, with the aim to better understand a possible in vivo mechanism of action. MFAT and LP specimens from 17 human donors were investigated side by side. During a long-term culture in serum-free medium, we found that the total cell number as well the MSC content in MFAT decreased more slowly if compared to those from LP specimens. The analysis of cytokines and growth factors secreted into the conditioned medium (CM) was similar in MFAT and LP during the first week of culture, but the total amount of cytokines secreted by LP decreased much more rapidly than those produced by MFAT during prolonged culture (up to 28 days). Similarly, the addition of MFAT-CM recovered at early (3-7 days) and late stage (14-28 days) of culture strongly inhibited inflammatory function of U937 monocyte cell line, whereas the anti-inflammatory activity of LP-CM was drastically reduced after only 7 days of culture. We conclude that MFAT is an effective preparation with a long-lasting anti-inflammatory activity probably mediated by a long-term survival of their MSC content that releases a combination of cytokines that affect several mechanisms involved in inflammation processes.

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Effects of diet and vitamin E supplementation on the distribution of vitamin E in plasma, muscle, liver and adipose tissue in lambs fed on concentrates alone or with grass silage

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200012217 ◽

2003 ◽

Vol 2003 ◽

pp. 62-62

Author(s):

E. Kasapidou ◽

R.I. Richardson ◽

J.D. Wood ◽

L.A. Sinclair ◽

R.G. Wilkinson ◽

...

Keyword(s):

Adipose Tissue ◽

Vitamin E ◽

Slow Release ◽

Short Term ◽

Grass Silage ◽

Poor Absorption ◽

Fast Release ◽

Vitamin E Status

Vitamin E protects the animal from oxidative stress in vivo and when it is administered at supranutritional levels it enhances the oxidative stability of meat. Studies have shown that poor absorption of vitamin E often occurs when concentrates are fed to lambs. Distribution of vitamin E in plasma, skeletal muscle, liver (short-term and fast release depot) and adipose tissue (long-term and slow release depot) provides useful information about the overall vitamin E status of the animals. This work studied the distribution of vitamin E in the tissues after supplementation in relation to diet and to the dietary level.

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