Mesenchymal Stromal Cells (MSCs): a promising tool for cell-based angiogenic therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Cristiana Ulpiano ◽  
Cláudia L. da Silva ◽  
Gabriel A. Monteiro
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Genetic Material ◽  
Biologically Active ◽  
Human Mscs ◽  
Comprehensive Overview ◽  
Cell Functions ◽  
Cell Based Therapy ◽  
Wide Range

: The Mesenchymal stromal cells (MSCs) are a diverse subset of adult multipotent precursors, known for their potential therapeutic properties in regenerative medicine mainly sustained by paracrine effects, through secretion of a variety of biologically active molecules. MSC secretome includes a wide range of soluble protein factors, composed of growth factors and cytokines, and vesicular components, which transfer proteins and genetic material modulating the host microenvironment. In particular, MSC-derived secretome mediates the different steps of the angiogenic process, inducing endothelial cell functions in vitro and promoting angiogenesis in vivo. As a result, MSCs have been widely explored as a promising cell-based therapy in diseases caused by insufficient angiogenesis. Numerous studies of myocardial infarction, ischemic stroke and critical limb ischemia in animals have shown that human MSCs can enhance angiogenesis and accelerate tissue regeneration. This extensive preclinical work encouraged the study of these remarkable cells for the treatment of these disorders in human clinical settings. The present review provides a comprehensive overview of the pro-angiogenic potential of MSCs and paracrine effectors of their secretome. In addition, bioengineering strategies including ex vivo preconditioning and genetic modification approaches, to enhance MSC innate angiogenic properties, and thereby therapeutic potency, will be presented. Finally, an update on completed preclinical and clinical studies with MSCs for the treatment of ischemia-related diseases will be discussed.

scholarly journals A chemically defined biomimetic surface for enhanced isolation efficiency of high-quality human mesenchymal stromal cells under xeno-/serum-free conditions

2021 ◽  
Author(s):  
Kristina Thamm ◽  
Kristin Moebus ◽  
Russel Towers ◽  
Stefan Baertschi ◽  
Richard Wetzel ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Cell Types ◽  
Isolation Procedure ◽  
High Yield ◽  
Human Mscs ◽  
Isolated Cells ◽  
Serum Free ◽  
Biomimetic Surface

Mesenchymal stromal cells (MSCs) are one of the most frequently used cell types in regenerative medicine and cell therapy. Generating sufficient cell numbers for MSC-based therapies is constrained by: 1) their low abundance in tissues of origin, which imposes the need for significant ex vivo cell amplification, 2) donor-specific characteristics including MSC frequency/quality that decline with disease state and increasing age, 3) cellular senescence, which is promoted by extensive cell expansion and results in decreased therapeutic functionality. The final yield of a manufacturing process is therefore primarily determined by the applied isolation procedure and its efficiency in isolating therapeutically active cells from donor tissue. To date, MSCs are predominantly isolated using media supplemented with either serum or its derivatives, which pose safety and consistency issues. To overcome those limitations while enabling robust MSC production with constant high yield and quality, we developed a chemically defined biomimetic surface coating, called isoMATRIX, that facilitates the isolation of significantly higher numbers of MSCs in xeno-/serum-free and chemically defined conditions. The isolated cells display a smaller cell size and higher proliferation rate than those derived from a serum-containing isolation procedure and a strong immunomodulatory capacity. In sum, the isoMATRIX promotes enhanced xeno-, serum-free, or chemically defined isolation of human MSCs and supports consistent and reliable cell performance for improved stem cell-based therapies.

scholarly journals Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 68
Author(s):  
Fulvio Massaro ◽  
Florent Corrillon ◽  
Basile Stamatopoulos ◽  
Nathalie Meuleman ◽  
Laurence Lagneaux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Communication ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Wide Range ◽  
Major Player

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

scholarly journals Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells

2021 ◽  
Author(s):  
Valentina Orticelli ◽  
Andrea Papait ◽  
Elsa Vertua ◽  
Patrizia Bonassi Signoroni ◽  
Pietro Romele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Stem

Evaluation of Potential Application of Wharton’s Jelly-Derived Human Mesenchymal Stromal Cells and its Conditioned Media for Dermal Regeneration using Rat Wound Healing Model

2021 ◽  
pp. 1-14
Author(s):  
Caroline Mathen ◽  
Mrunal Ghag Sawant ◽  
Raghubansh Gupta ◽  
Wilfrid Dsouza ◽  
Shilpa G. Krishna
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Wound Care ◽  
Free Cell ◽  
Conditioned Media ◽  
Human Umbilical Cord ◽  
Human Mscs ◽  
Wound Model

Mesenchymal stromal cells and the derived conditioned media represent an area of tremendous medical interest and, among other clinical applications, are currently being extensively explored for wound healing. The aim of this study was to comparatively evaluate the wound healing potential of xeno-free human umbilical cord-derived mesenchymal stromal cells (MSCs) and the conditioned media (CM) in a full-thickness excision wound model in rats. The evaluation parameters included rate of wound healing, serum cytokine analyses, collagen content, histopathology, and hyperspectral imaging as an independent qualitative and quantitative tool. Both the cell-based and cell-free approaches scored better in lower inflammation, as evidenced in lower IL-10 and stable IL-6 levels, and improved rate of wound healing (<i>p</i> &#x3c; 0.0001). More importantly, no adverse reaction or rejection was observed although human MSCs and CM were used in a xenogeneic model. The presence of hFGF, hHGF, hGCSF, hIL-1Ra, hVEGF, and hIL-6 in the secretome may elucidate the regenerative potential of the xeno-free cell-based and cell-free approaches which have translational value for advanced wound care. The results revealed the therapeutic potential of both the cell-based and cell-free approaches for wound healing.

scholarly journals The oncometabolite R-2-hydroxyglutarate dysregulates the differentiation of human mesenchymal stromal cells via inducing DNA hypermethylation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lizhen Liu ◽  
Kaimin Hu ◽  
Jingjing Feng ◽  
Huafang Wang ◽  
Shan Fu ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chondrogenic Differentiation ◽  
Cell Counting ◽  
Human Mscs ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dna Hypermethylation ◽  
Cartilaginous Tumors

Abstract Background Isocitrate dehydrogenase (IDH1/2) gene mutations are the most frequently observed mutations in cartilaginous tumors. The mutant IDH causes elevation in the levels of R-enantiomer of 2-hydroxylglutarate (R-2HG). Mesenchymal stromal cells (MSCs) are reasonable precursor cell candidates of cartilaginous tumors. This study aimed to investigate the effect of oncometabolite R-2HG on MSCs. Methods Human bone marrow MSCs treated with or without R-2HG at concentrations 0.1 to 1.5 mM were used for experiments. Cell Counting Kit-8 was used to detect the proliferation of MSCs. To determine the effects of R-2HG on MSC differentiation, cells were cultured in osteogenic, chondrogenic and adipogenic medium. Specific staining approaches were performed and differentiation-related genes were quantified. Furthermore, DNA methylation status was explored by Illumina array-based arrays. Real-time PCR was applied to examine the signaling component mRNAs involved in. Results R-2HG showed no influence on the proliferation of human MSCs. R-2HG blocked osteogenic differentiation, whereas promoted adipogenic differentiation of MSCs in a dose-dependent manner. R-2HG inhibited chondrogenic differentiation of MSCs, but increased the expression of genes related to chondrocyte hypertrophy in a lower concentration (1.0 mM). Moreover, R-2HG induced a pronounced DNA hypermethylation state of MSC. R-2HG also improved promotor methylation of lineage-specific genes during osteogenic and chondrogenic differentiation. In addition, R-2HG induced hypermethylation and decreased the mRNA levels of SHH, GLI1and GLI2, indicating Sonic Hedgehog (Shh) signaling inhibition. Conclusions The oncometabolite R-2HG dysregulated the chondrogenic and osteogenic differentiation of MSCs possibly via induction of DNA hypermethylation, improving the role of R-2HG in cartilaginous tumor development.

The role of children's bone marrow mesenchymal stromal cells in the ex vivo expansion of autologous and allogeneic hematopoietic stem cells

2015 ◽  
Vol 39 (10) ◽  
pp. 1099-1110 ◽  
Author(s):  
Iordanis Pelagiadis ◽  
Eftichia Stiakaki ◽  
Christianna Choulaki ◽  
Maria Kalmanti ◽  
Helen Dimitriou
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Stem

scholarly journals Ex vivo MRI cell tracking of autologous mesenchymal stromal cells in an ovine osteochondral defect model

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Hareklea Markides ◽  
Karin J. Newell ◽  
Heike Rudorf ◽  
Lia Blokpoel Ferreras ◽  
James E. Dixon ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Tracking ◽  
Osteochondral Defect ◽  
Ex Vivo ◽  
Defect Model

scholarly journals Process data of allogeneic ex vivo-expanded ABCB5+ mesenchymal stromal cells for human use: Off-the-shelf GMP-manufactured donor-independent ATMP

2020 ◽  
Author(s):  
Seda Ballikaya ◽  
Samar Sadeghi ◽  
Elke Niebergall-Roth ◽  
Laura Nimtz ◽  
Jens Frindert ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Manufacturing Process ◽  
Ex Vivo ◽  
Good Manufacturing Practice ◽  
Process Data ◽  
Advanced Therapy Medicinal Product ◽  
Drug Products ◽  
Advanced Therapy ◽  
Immunomagnetic Isolation

Abstract Background: Human dermal mesenchymal stromal cells (MSCs) expressing the ATP-binding cassette (ABC) efflux transporter ABCB5 represent an easily accessible MSC population that, based on preclinical and first-in-human data, holds significant promise to treat a broad spectrum of conditions associated not only with skin-related but also systemic inflammatory and/or degenerative processes.Methods: We developed and validated Good Manufacturing Practice-compliant expansion and manufacturing process by which ABCB5+ MSCs derived from surgical discard skin tissues are processed to an advanced-therapy medicinal product (ATMP) for clinical use. Enrichment for ABCB5+ MSCs is achieved in a three-step process involving plastic adherence selection, expansion in a highly efficient MSC-selecting medium and immunomagnetic isolation of the ABCB5+ cells from the mixed culture.Results: Product Quality Review data covering 324 cell expansions, 728 ABCB5+ MSC isolations, 66 ABCB5+ MSC batches and 85 final drug products reveal high process robustness and reproducible, reliable quality of the manufactured cell therapy product.Conclusion: We have successfully established an expansion and manufacturing process that enables the generation of homogenous ABCB5+ MSC populations of proven biological activity manufactured as a standardized, donor-independent, highly pure and highly functional off-the-shelf available ATMP, which is currently tested in multiple clinical trials.

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