Editorial

3 pages, 168 KiB

Open AccessEditorial

Recent Advances in Translational Adipose-Derived Stem Cell Biology

by Darius Widera

Biomolecules 2021, 11(11), 1660; https://doi.org/10.3390/biom11111660 - 09 Nov 2021

Cited by 1 | Viewed by 1362

Multipotent mesenchymal stem cells/marrow stromal cells (MSCs), originally discovered in the bone marrow by Alexander Friedenstein as early as 1968 [...] Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

Research

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14 pages, 2151 KiB

Open AccessArticle

Time-Dependent Reduction of Calcium Oscillations in Adipose-Derived Stem Cells Differentiating towards Adipogenic and Osteogenic Lineage

by Enrico C. Torre, Mesude Bicer, Graeme S. Cottrell, Darius Widera and Francesco Tamagnini

Biomolecules 2021, 11(10), 1400; https://doi.org/10.3390/biom11101400 - 23 Sep 2021

Cited by 4 | Viewed by 2364

Abstract

Adipose-derived mesenchymal stromal cells (ASCs) are multipotent stem cells which can differentiate into various cell types, including osteocytes and adipocytes. Due to their ease of harvesting, multipotency, and low tumorigenicity, they are a prime candidate for the development of novel interventional approaches in [...] Read more.

Adipose-derived mesenchymal stromal cells (ASCs) are multipotent stem cells which can differentiate into various cell types, including osteocytes and adipocytes. Due to their ease of harvesting, multipotency, and low tumorigenicity, they are a prime candidate for the development of novel interventional approaches in regenerative medicine. ASCs exhibit slow, spontaneous Ca²⁺ oscillations and the manipulation of Ca²⁺ signalling via electrical stimulation was proposed as a potential route for promoting their differentiation in vivo. However, the effects of differentiation-inducing treatments on spontaneous Ca²⁺ oscillations in ASCs are not yet fully characterised. In this study, we used 2-photon live Ca²⁺ imaging to assess the fraction of cells showing spontaneous oscillations and the frequency of the oscillation (measured as interpeak interval—IPI) in ASCs undergoing osteogenic or adipogenic differentiation, using undifferentiated ASCs as controls. The measurements were carried out at 7, 14, and 21 days in vitro (DIV) to assess the effect of time in culture on Ca²⁺ dynamics. We observed that both time and differentiation treatment are important factors associated with a reduced fraction of cells showing Ca²⁺ oscillations, paralleled by increased IPI times, in comparison with untreated ASCs. Both adipogenic and osteogenic differentiation resulted in a reduction in Ca²⁺ dynamics, such as the fraction of cells showing intracellular Ca²⁺ oscillations and their frequency. Adipogenic differentiation was associated with a more pronounced reduction of Ca²⁺ dynamics compared to cells differentiating towards the osteogenic fate. Changes in Ca²⁺ associated oscillations with a specific treatment had already occurred at 7 DIV. Finally, we observed a reduction in Ca²⁺ dynamics over time in untreated ASCs. These data suggest that adipogenic and osteogenic differentiation cell fates are associated with specific changes in spontaneous Ca²⁺ dynamics over time. While this observation is interesting and provides useful information to understand the functional correlates of stem cell differentiation, further studies are required to clarify the molecular and mechanistic correlates of these changes. This will allow us to better understand the causal relationship between Ca²⁺ dynamics and differentiation, potentially leading to the development of novel, more effective interventions for both bone regeneration and control of adipose growth. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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15 pages, 5124 KiB

Open AccessArticle

Chronic DDE Exposure Modifies Mitochondrial Respiration during Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Mature Adipocytes

by Iva Kladnicka, Miroslava Cedikova, Jan Jedlicka, Michaela Kohoutova, Ludek Muller, Iveta Plavinova, Michaela Kripnerova, Monika Bludovska, Jitka Kuncova and Dana Mullerova

Biomolecules 2021, 11(8), 1068; https://doi.org/10.3390/biom11081068 - 21 Jul 2021

Cited by 4 | Viewed by 2248

Abstract

The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p′-DDE) exposure of [...] Read more.

The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p′-DDE) exposure of human adipose-derived mesenchymal stem cells committed to adipogenesis on mitochondrial oxygen consumption on days 4, 10, and 21. In addition, the mitochondrial membrane potential (MMP), the quality of the mitochondrial network, and lipid accumulation in maturing cells were evaluated. Compared to control differentiating adipocytes, exposure to p,p′-DDE at 1 μM concentration significantly increased basal (routine) mitochondrial respiration, ATP-linked oxygen consumption and MMP of intact cells on day 21 of adipogenesis. In contrast, higher pollutant concentration seemed to slow down the gradual increase in ATP-linked oxygen consumption typical for normal adipogenesis. Organochlorine p,p′-DDE did not alter citrate synthase activity. In conclusion, in vitro 1 μM p,p′-DDE corresponding to human exposure is able to increase the mitochondrial respiration per individual mitochondrion at the end of adipocyte maturation. Our data reveal that long-lasting exposure to p,p′-DDE could interfere with the metabolic programming of mature adipocytes. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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18 pages, 5647 KiB

Open AccessArticle

Electrical Stimulation of Adipose-Derived Stem Cells in 3D Nanofibrillar Cellulose Increases Their Osteogenic Potential

by Mesude Bicer, Jonathan Sheard, Donata Iandolo, Samuel Y. Boateng, Graeme S. Cottrell and Darius Widera

Biomolecules 2020, 10(12), 1696; https://doi.org/10.3390/biom10121696 - 18 Dec 2020

Cited by 15 | Viewed by 4254

Abstract

Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of [...] Read more.

Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of viable, autologous bone grafts is limited making alternative cell-based strategies a promising therapeutic alternative. Adipose-derived stem cells (ASCs) are a readily available population of mesenchymal stem/stromal cells (MSCs) that can be isolated within minimally invasive surgery. This ease of availability and their ability to undergo osteogenic differentiation makes ASCs promising candidates for cell-based therapies for bone fractures. Recent studies have suggested that both exposure to electrical fields and cultivation in 3D can positively affect osteogenic potential of MSCs. To elucidate the osteoinductive potential of a combination of these biophysical cues on ASCs, cells were embedded within anionic nanofibrillar cellulose (aNFC) hydrogels and exposed to electrical stimulation (ES) for up to 21 days. ES was applied to ASCs in 2D and 3D at a voltage of 0.1 V/cm with a duration of 0.04 ms, and a frequency of 10 Hz for 30 min per day. Exposure of ASCs to ES in 3D resulted in high alkaline phosphatase (ALP) activity and in an increased mineralisation evidenced by Alizarin Red S staining. Moreover, ES in 3D aNFC led to an increased expression of the osteogenic markers osteopontin and osteocalcin and a rearrangement and alignment of the actin cytoskeleton. Taken together, our data suggest that a combination of ES with 3D cell culture can increase the osteogenic potential of ASCs. Thus, exposure of ASCs to these biophysical cues might improve the clinical outcomes of regenerative therapies in treatment of osteoporotic fractures. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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13 pages, 1487 KiB

Open AccessArticle

An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury

by Ibtesam R. T. Al Delfi, Chelsea R. Wood, Louis D. V. Johnson, Martyn D. Snow, John F. Innes, Peter Myint and William E. B. Johnson

Biomolecules 2020, 10(9), 1301; https://doi.org/10.3390/biom10091301 - 09 Sep 2020

Cited by 9 | Viewed by 2483

Abstract

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human [...] Read more.

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and βIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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16 pages, 2192 KiB

Open AccessFeature PaperArticle

Adipose Tissue-Derived Stem Cells Retain Their Adipocyte Differentiation Potential in Three-Dimensional Hydrogels and Bioreactors

by Benjamen T. O'Donnell, Sara Al-Ghadban, Clara J. Ives, Michael P. L'Ecuyer, Tia A. Monjure, Monica Romero-Lopez, Zhong Li, Stuart B. Goodman, Hang Lin, Rocky S. Tuan and Bruce A. Bunnell

Biomolecules 2020, 10(7), 1070; https://doi.org/10.3390/biom10071070 - 17 Jul 2020

Cited by 26 | Viewed by 4218

Abstract

Osteoarthritis (OA) is a common joint disorder with a significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose [...] Read more.

Osteoarthritis (OA) is a common joint disorder with a significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose tissue has recently been highlighted as a major contributor to OA through strong inflammation mediating effects. In this study, methacrylated gelatin (GelMA) constructs seeded with adipose tissue-derived mesenchymal stem cells (ASCs) and cultured in a 3D printed bioreactor were investigated for use in microphysiological systems to model adipose tissue in the knee joint. Four patient-derived ASC populations were seeded at a density of 20 million cells/mL in GelMA. Live/Dead and boron-dipyrromethene/4′,6-diamidino-2-phenylindole (BODIPY/DAPI) staining of cells within the constructs demonstrated robust cell viability after 28 days in a growth (control) medium, and robust cell viability and lipid accumulation in adipogenic differentiation medium. qPCR gene expression analysis and protein analysis demonstrated an upregulated expression of key adipogenesis-associated genes. Overall, these data indicate that ASCs retain their adipogenic potential when seeded within GelMA hydrogels and cultured within perfusion bioreactors, and thus can be used in a 3D organ-on-a-chip system to study the role of the IPFP in the pathobiology of the knee OA. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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Review

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13 pages, 734 KiB

Open AccessReview

Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine

by Wee Kiat Ong, Smarajit Chakraborty and Shigeki Sugii

Biomolecules 2021, 11(7), 918; https://doi.org/10.3390/biom11070918 - 22 Jun 2021

Cited by 47 | Viewed by 5830

Abstract

Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and [...] Read more.

Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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24 pages, 1529 KiB

Open AccessEditor’s ChoiceReview

Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”

by Anna Trzyna and Agnieszka Banaś-Ząbczyk

Biomolecules 2021, 11(6), 878; https://doi.org/10.3390/biom11060878 - 13 Jun 2021

Cited by 79 | Viewed by 6803

Abstract

Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides [...] Read more.

Adipose-derived stem cells (ASCs) secrete many cytokines, proteins, growth factors, and extracellular vesicles with beneficial outcomes that can be used in regenerative medicine. It has great potential, and the development of new treatment strategies using the ASCs secretome is of global interest. Besides cytokines, proteins, and growth factors, the therapeutic effect of secretome is hidden in non-coding RNAs such as miR-21, miR-24, and miR-26 carried via exosomes secreted by adequate cells. The whole secretome, including ASC-derived exosomes (ASC-exos) has been proven in many studies to have immunomodulatory, proangiogenic, neurotrophic, and epithelization activity and can potentially be used for neurodegenerative, cardiovascular, respiratory, inflammatory, and autoimmune diseases as well as wound healing treatment. Due to limitations in the use of stem cells in cell-based therapy, its secretome with emphasis on exosomes seems to be a reasonable and safer alternative with increased effectiveness and fewer side effects. Moreover, the great advantage of cell-free therapy is the possibility of biobanking the ASCs secretome. In this review, we focus on the current state of knowledge on the use of the ASCs secretome in stem cell-free therapy. Full article

(This article belongs to the Special Issue Recent Advances in Translational Adipose-Derived Stem Cell Biology)

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