Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF,n=4) or allogeneic cultured adipose-derived stem cells (ASCs,n=5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases.

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Characteristics and Potentiality of Human Adipose-Derived Stem Cells (hASCs) Obtained from Enzymatic Digestion of Fat Graft

Cells ◽

10.3390/cells8030282 ◽

2019 ◽

Vol 8 (3) ◽

pp. 282 ◽

Cited By ~ 28

Author(s):

Pietro Gentile ◽

Maria Piccinno ◽

Claudio Calabrese

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Ex Vivo ◽

Stromal Vascular Fraction ◽

Enzymatic Digestion ◽

Histological Evaluation ◽

Fat Graft ◽

Adipose Derived Stem Cells ◽

Differentiation Potential ◽

New Therapeutic Approaches

Human adipose-derived stem cells localize in the stromal-vascular portion, and can be ex vivo isolated using a combination of washing steps and enzymatic digestion. For this study, we undertook a histological evaluation of traditional fat graft compared with fat graft enriched with stromal vascular fraction cells isolated by the Celution™ system to assess the interactions between cells and adipose tissue before the breast injection. In addition, we reported on histological analyses of biopsies derived from fat grafted (traditional or enriched with SVFs) in the breast in order to assess the quality of the adipose tissue, fibrosis and vessels. The hASCs derived from enzymatic digestion were systematically characterized for growth features, phenotype and multi-potent differentiation potential. They fulfill the definition of mesenchymal stem cells, albeit with a higher neural phenotype profile. These cells also express genes that constitute the core circuitry of self-renewal such as OCT4, SOX2, NANOG and neurogenic lineage genes such as NEUROD1, PAX6 and SOX3. Such findings support the hypothesis that hASCs may have a potential usefulness in neurodegenerative conditions. These data can be helpful for the development of new therapeutic approaches in personalized medicine to assess safety and efficacy of the breast reconstruction.

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Adipose-Based Therapies for Knee Pain—Fat or Fiction

The Journal of Knee Surgery ◽

10.1055/s-0038-1672155 ◽

2018 ◽

Vol 32 (01) ◽

pp. 055-064 ◽

Cited By ~ 4

Author(s):

Yoshiharu Shimozono ◽

Lisa Fortier ◽

Donald Brown ◽

John Kennedy

Keyword(s):

Stem Cells ◽

Adverse Reactions ◽

Therapeutic Potential ◽

Stromal Vascular Fraction ◽

The United States ◽

Adipose Derived Stem Cells ◽

Cell Therapies ◽

Knee Oa ◽

Chondrogenic Potential ◽

Enzymatic Isolation

AbstractRegenerative cell therapies are emerging as promising treatments for numerous musculoskeletal conditions, including knee osteoarthritis (OA). Adipose-derived stem cells and possibly other adipose-based therapies have a greater chondrogenic potential than stem cells derived from bone marrow, and thus a lot of attention is being placed on them as potential regenerative agents in the treatment of knee OA. Several types of adipose-based therapies have good basic science and preclinical data supporting their translation to human therapeutic intervention. Cultured, adipose-derived stem cells appear to be good source of bioactive cells with convenient accessibility, relative abundance, and well-documented regenerative capacity. Non-culture expanded adipose-based therapy, in the forms of stromal vascular fraction and most recently micronized adipose tissue (MAT), have been utilized in patients to treat OA and other cartilage abnormalities with encouraging preliminary data. These adipose-based therapies have shown a lot of therapeutic potential; however, because of the regulatory restrictions on enzymatic isolation and cell expansion, only MAT is currently available in clinical practice in the United States. While no serious adverse reactions have been reported, adipose-derived therapies also have the potential for adverse reactions including inflammation and infection. The current review provides an update on the latest research and presents this evidence on the therapeutic potential of adipose-based therapies in the treatment of knee OA.

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Increase in Leptin and PPAR-γ Gene Expression in Lipedema Adipocytes Differentiated in vitro from Adipose-Derived Stem Cells

Cells ◽

10.3390/cells9020430 ◽

2020 ◽

Vol 9 (2) ◽

pp. 430 ◽

Cited By ~ 6

Author(s):

Sara Al-Ghadban ◽

Zaidmara T. Diaz ◽

Hallie J. Singer ◽

Karya B. Mert ◽

Bruce A. Bunnell

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Adipogenic Differentiation ◽

Stromal Vascular Fraction ◽

Connective Tissue Disorder ◽

Adipose Derived Stem Cells ◽

Differentiation Potential ◽

Ppar Γ ◽

Expression Of Genes

Lipedema is a painful loose connective tissue disorder characterized by a bilaterally symmetrical fat deposition in the lower extremities. The goal of this study was to characterize the adipose-derived stem cells (ASCs) of healthy and lipedema patients by the expression of stemness markers and the adipogenic and osteogenic differentiation potential. Forty patients, 20 healthy and 20 with lipedema, participated in this study. The stromal vascular fraction (SVF) was obtained from subcutaneous thigh (SVF-T) and abdomen (SVF-A) fat and plated for ASCs characterization. The data show a similar expression of mesenchymal markers, a significant increase in colonies (p < 0.05) and no change in the proliferation rate in ASCs isolated from the SVF-T or SVF-A of lipedema patients compared with healthy patients. The leptin gene expression was significantly increased in lipedema adipocytes differentiated from ASCs-T (p = 0.04) and the PPAR-γ expression was significantly increased in lipedema adipocytes differentiated from ASCs-A (p = 0.03) compared to the corresponding cells from healthy patients. No significant changes in the expression of genes associated with inflammation were detected in lipedema ASCs or differentiated adipocytes. These results suggest that lipedema ASCs isolated from SVF-T and SVF-A have a higher adipogenic differentiation potential compared to healthy ASCs.

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Characterization of human adipose-derived stem cells

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000700007 ◽

2012 ◽

Vol 27 (7) ◽

pp. 471-476 ◽

Cited By ~ 19

Author(s):

Silvana Gaiba ◽

Lucimar Pereira de França ◽

Jerônimo Pereira de França ◽

Lydia Masako Ferreira

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chondrogenic Differentiation ◽

Therapeutic Potential ◽

Culture Conditions ◽

In Vitro Cultivation ◽

Neural Cells ◽

Adipose Derived Stem Cells ◽

Differentiation Potential

PURPOSE: There is a growing scientific interest in the plasticity and therapeutic potential of adipose-derived stem cells (ASCs), which are multipotent and abundant in adipose tissue and can differentiate in vitro into multiple lineages, including adipocytes, chondrocytes, osteoblasts, neural cells, endothelial cells and cardiomyocytes. The aim of this study was to isolate, cultivate and identify ASCs. METHODS: Human adipose precursor cells were obtained from subcutaneous abdominal tissue. Recently dispersed cells were separated by density centrifugation gradient, cultured and then analyzed. RESULTS: Human ASCs were able to replicate in our culture conditions. The cells maintained their phenotypes throughout the studied period on different passages confirming they suitability for in vitro cultivation. We also induced their adipogenic, osteogenic and chondrogenic differentiation, verifying their mesenchymal stem cells potentiality in vitro. Flow cytometry results showed that these cells expressed CD73, CD90 and CD105, (mesenchymal stem-cells markers), contrasting with the lack of expression of CD16, CD34 and CD45 (hematopoietic cells markers). CONCLUSION: It was possible to isolate human adipose-derived stem cells by in vitro cultivation without adipogenic induction, maintaining their functional integrity and high proliferation levels. The cells demonstrated adipogenic, osteogenic and chondrogenic differentiation potential in vitro.

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Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190222201749 ◽

2019 ◽

Vol 14 (4) ◽

pp. 327-336 ◽

Cited By ~ 9

Author(s):

Carl R. Harrell ◽

Marina Gazdic ◽

Crissy Fellabaum ◽

Nemanja Jovicic ◽

Valentin Djonov ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Animal Models ◽

Amniotic Fluid ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Therapeutic Effects ◽

Differentiation Potential ◽

Differentiation Capacity ◽

Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

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A NOTCH1/LSD1/BMP2 co-regulatory network mediated by miR-137 negatively regulates osteogenesis of human adipose-derived stem cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02495-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Cong Fan ◽

Xiaohan Ma ◽

Yuejun Wang ◽

Longwei Lv ◽

Yuan Zhu ◽

...

Keyword(s):

Stem Cells ◽

Osteoblastic Differentiation ◽

Negative Control ◽

Bone Morphogenetic Protein 2 ◽

Luciferase Reporter ◽

Adipose Derived Stem Cells ◽

Differentiation Potential ◽

Lineage Differentiation ◽

Morphogenetic Protein ◽

Genes Expression

Abstract Background MicroRNAs have been recognized as critical regulators for the osteoblastic lineage differentiation of human adipose-derived stem cells (hASCs). Previously, we have displayed that silencing of miR-137 enhances the osteoblastic differentiation potential of hASCs partly through the coordination of lysine-specific histone demethylase 1 (LSD1), bone morphogenetic protein 2 (BMP2), and mothers against decapentaplegic homolog 4 (SMAD4). However, still numerous molecules involved in the osteogenic regulation of miR-137 remain unknown. This study aimed to further elucidate the epigenetic mechanisms of miR-137 on the osteogenic differentiation of hASCs. Methods Dual-luciferase reporter assay was performed to validate the binding to the 3′ untranslated region (3′ UTR) of NOTCH1 by miR-137. To further identify the role of NOTCH1 in miR-137-modulated osteogenesis, tangeretin (an inhibitor of NOTCH1) was applied to treat hASCs which were transfected with miR-137 knockdown lentiviruses, then together with negative control (NC), miR-137 overexpression and miR-137 knockdown groups, the osteogenic capacity and possible downstream signals were examined. Interrelationships between signaling pathways of NOTCH1-hairy and enhancer of split 1 (HES1), LSD1 and BMP2-SMADs were thoroughly investigated with separate knockdown of NOTCH1, LSD1, BMP2, and HES1. Results We confirmed that miR-137 directly targeted the 3′ UTR of NOTCH1 while positively regulated HES1. Tangeretin reversed the effects of miR-137 knockdown on osteogenic promotion and downstream genes expression. After knocking down NOTCH1 or BMP2 individually, we found that these two signals formed a positive feedback loop as well as activated LSD1 and HES1. In addition, LSD1 knockdown induced NOTCH1 expression while suppressed HES1. Conclusions Collectively, we proposed a NOTCH1/LSD1/BMP2 co-regulatory signaling network to elucidate the modulation of miR-137 on the osteoblastic differentiation of hASCs, thus providing mechanism-based rationale for miRNA-targeted therapy of bone defect.

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Therapeutic Potential of Magnetic Nanoparticle-Based Human Adipose-Derived Stem Cells in a Mouse Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22020654 ◽

2021 ◽

Vol 22 (2) ◽

pp. 654

Author(s):

Ka Young Kim ◽

Keun-A Chang

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Magnetic Nanoparticles ◽

Substantia Nigra ◽

Mouse Model ◽

Magnetic Nanoparticle ◽

Imaging System ◽

Therapeutic Potential ◽

Adipose Derived Stem Cells

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.

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Therapeutic potential of adipose-derived stem cells and macrophages for ischemic skeletal muscle repair

Regenerative Medicine ◽

10.2217/rme-2016-0094 ◽

2017 ◽

Vol 12 (2) ◽

pp. 153-167 ◽

Cited By ~ 13

Author(s):

Viktoriya Rybalko ◽

Pei-Ling Hsieh ◽

Laura M Ricles ◽

Eunna Chung ◽

Roger P Farrar ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Therapeutic Potential ◽

Adipose Derived Stem Cells ◽

Muscle Repair

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Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

Stem Cells International ◽

10.1155/2017/6072406 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Gayathri Subramanian ◽

Alexander Stasuk ◽

Mostafa Elsaadany ◽

Eda Yildirim-Ayan

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Expression Profiles ◽

Three Dimensional ◽

Uniaxial Tensile ◽

Adipose Derived Stem Cells ◽

Collagen Scaffolds ◽

Differentiation Potential ◽

Tenogenic Differentiation ◽

Matrix Organization

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

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