Immunomodulatory properties of adipose stem cells in vivo: Preclinical and clinical applications

Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs afterin vivoimplantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5% oxygen were compared to eqUCM-MSCs under standard conditions. Equine UCM-MSCs formed spheroids on chitosan but yielded 72% less DNA than standard eqUCM-MSCs. Expression ofSox2,Oct4, andNanogwas 4 to 10 times greater in conditioned cells at day 7. Fluorescence-labeled cells cultured for 7 days under standard conditions or on chitosan films under hypoxia were compared in a bilateral patellar tendon defect model in rats. Fluorescence was present in all treated tendons, but the modulus of elasticity under tension was greater in tendons treated with conditioned cells. Chitosan and hypoxia affected cell yield but improved the stemness of eqUCM-MSCs and their contribution to the healing of tissues. Given the abundance of allogenic cells, these properties are highly relevant to clinical applications and outweigh the negative impact on cell proliferation.

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Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells

Journal of Clinical Medicine ◽

10.3390/jcm9020310 ◽

2020 ◽

Vol 9 (2) ◽

pp. 310 ◽

Cited By ~ 1

Author(s):

David Alfaro ◽

Mariano R. Rodríguez-Sosa ◽

Agustín G. Zapata

Keyword(s):

Stem Cells ◽

Therapeutic Agents ◽

Current Evidence ◽

Specific Cell ◽

Heterogeneous Cell Population ◽

Proliferation And Differentiation ◽

Ephrin Ligands ◽

Immunomodulatory Properties ◽

Stromal Stem Cells

Mesenchymal stromal/stem cells (MSCs) have emerged as important therapeutic agents, owing to their easy isolation and culture, and their remarkable immunomodulatory and anti-inflammatory properties. However, MSCs constitute a heterogeneous cell population which does not express specific cell markers and has important problems for in vivo homing, and factors regulating their survival, proliferation, and differentiation are largely unknown. Accordingly, in the present article, we review the current evidence on the relationships between Eph kinase receptors, their ephrin ligands, and MSCs. These molecules are involved in the adult homeostasis of numerous tissues, and we and other authors have demonstrated their expression in human and murine MSCs derived from both bone marrow and adipose tissue, as well as their involvement in the MSC biology. We extend these studies providing new results on the effects of Eph/ephrins in the differentiation and immunomodulatory properties of MSCs.

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Monodispersed β‐Glycerophosphate‐Decorated Bioactive Glass Nanoparticles Reinforce Osteogenic Differentiation of Adipose Stem Cells and Bone Regeneration In Vivo

Particle & Particle Systems Characterization ◽

10.1002/ppsc.201900462 ◽

2020 ◽

Vol 37 (4) ◽

pp. 1900462

Author(s):

Yi Guo ◽

Yumeng Xue ◽

Juan Ge ◽

Bo Lei

Keyword(s):

Stem Cells ◽

Bioactive Glass ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Adipose Stem Cells

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Induction of Indoleamine 2,3-Dioxygenase Expression by Interferon-g in Human Mesenchymal Stem Cells Inhibits Graft Versus Host Disease

Blood ◽

10.1182/blood.v118.21.4698.4698 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4698-4698

Author(s):

Myoung Woo Lee ◽

Dae Seong Kim ◽

Hye Jin Kim ◽

Meong Hi Son ◽

Soo Hyun Lee ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Mesenchymal Stem Cells ◽

T Cell ◽

T Cell Proliferation ◽

Activated T Cells ◽

Graft Versus Host ◽

Ifn Γ ◽

Immunomodulatory Properties

Abstract Abstract 4698 Background: It is important to overcome the limitations such as graft rejection and graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. Purpose: In this study, we aimed to identify the immunomodulatory properties of human MSCs and to elucidate the possible mechanism of their properties for clinical treatment of allogeneic conflicts using MSCs. Materials & Methods: We conducted a comparative analysis about the immunomodulatory properties of MSCs derived from adult human tissues, including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ), in vitro and in vivo models. Results: AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed phytohemagglutinin (PHA)-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-g secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, expression of indoleamine 2,3-dioxygenase (IDO) increased in MSCs treated with IFN-γ via JAK/STAT1 signaling pathways. Treatment with anti-IFN-g antibodies, JAK1/2 inhibitor or STAT1 siRNA restored PHA-induced T-cell proliferation. Use of an antagonist, 1-methyl-L-tryptophan, also restored PHA-induced T-cell proliferation, suggesting that IDO contributes to IFN-g-induced immunosuppression in MSCs. Moreover, infusion of IFN-g-treated MSCs decreased symptoms for human peripheral blood-derived mononuclear cells-induced GvHD in NOD/SCID mice, which resulted in an increase of survival rate of in vivo GvHD model. Conclusion: These data indicate that IFN-γ produced by activated T-cells is correlated with induction of IDO expression in MSCs by IFN-γ receptor/JAK/STAT1 pathway, which resulted in suppression of T-cell proliferation. Our findings suggest that MSCs derived from BM, AT, CB, or WJ could be used for clinical treatment of allogeneic conflicts. Disclosures: No relevant conflicts of interest to declare.

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Development of Synthetic and Natural Materials for Tissue Engineering Applications Using Adipose Stem Cells

Stem Cells International ◽

10.1155/2016/5786257 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Yunfan He ◽

Feng Lu

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Tissue Regeneration ◽

Large Scale ◽

Clinical Applications ◽

Adipose Stem Cells ◽

Laboratory Research ◽

Engineering Applications ◽

Plastic And Reconstructive Surgery ◽

Relative Ease

Adipose stem cells have prominent implications in tissue regeneration due to their abundance and relative ease of harvest from adipose tissue and their abilities to differentiate into mature cells of various tissue lineages and secrete various growth cytokines. Development of tissue engineering techniques in combination with various carrier scaffolds and adipose stem cells offers great potential in overcoming the existing limitations constraining classical approaches used in plastic and reconstructive surgery. However, as most tissue engineering techniques are new and highly experimental, there are still many practical challenges that must be overcome before laboratory research can lead to large-scale clinical applications. Tissue engineering is currently a growing field of medical research; in this review, we will discuss the progress in research on biomaterials and scaffolds for tissue engineering applications using adipose stem cells.

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CRISPR Therapeutics: New Emerging Developments and Clinical Applications

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i5.5006 ◽

2021 ◽

Vol 11 (5) ◽

pp. 193-195

Author(s):

Kaiser Jay Aziz-Andersen

Keyword(s):

Stem Cells ◽

Gene Editing ◽

Ex Vivo ◽

Human Subjects ◽

Clinical Applications ◽

Approval Process ◽

Hematopoietic Stem ◽

Immune System Diseases ◽

Wide Range

CRISPR gene editing is a genetic engineering technique applied in clinical applications in which the genomes of living organisms may be modified. It is based on the principles of the CRISPR-Cas9 antiviral defense system. It is based on delivering the Cas9 nuclease complexed with a synthetic guide RNA into a living organism cell and that organisms’s genome can be “cut” and –“paste” at a desired location, allowing existing genes to be modified for desired outcome (i.e., CRISPR for Precision Medicine). CRISPR gene editing harnesses the natural defense mechanisms of some bacteria to cut human DNA strands. Then the DNA strand either heals itself or injects a new piece of DNA to mend the gap. Studies have been reported in Lung Cancer diagnosis and treatments. CRISPR-based engineering techniques have been developed for T Cells and Stem cells applications (i.e. Gene Corrections in Hematopoietic Stem Cells for the Treatment of Blood and Immune System Diseases). Even though earlier CRISPR methodologies were used for performing simple DNA edits, recent applications include the ability to delete genes or insert genes, and edit regulatory regions in a wide range of cell types. The role of CRISPR in human therapeutics is currently focused on utilizing CRISPR techniques to perform either in vivo editing of human cells–everything from the head, eye all the way to neurons and liver cells--or performing ex vivo therapies. The FDA’s new genomic CRISPR technology based products approval process begins with review and evaluation of preclinical studies in order to establish and characterize the proposed product’s safety profile. New genomic products must be shown to be safe and effective for the FDA approval process. The sponsor of the new genomic product must show that the product is safe and effective in human subjects.1

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Manufacturing and Banking Canine Adipose-Derived Mesenchymal Stem Cells for Veterinary Clinical Application

10.21203/rs.3.rs-64097/v3 ◽

2021 ◽

Author(s):

Huina Luo ◽

Dongsheng Li ◽

Zhisheng Chen ◽

Bingyun Wang ◽

Shengfeng Chen

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Normal Karyotype ◽

Clinical Applications ◽

Therapeutic Application ◽

Differentiation Potential ◽

Safety And Efficacy

Abstract BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in two cases treated with intravenously AD-MSCs. CONCLUSION: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.

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