scholarly journals Feline bone marrow-derived mesenchymal stromal cells (MSCs) show similar phenotype and functions with regards to neuronal differentiation as human MSCs

2012 ◽  
Vol 84 (2) ◽  
pp. 214-222 ◽  
Author(s):  
Jessian L. Munoz ◽  
Steven J. Greco ◽  
Shyam A. Patel ◽  
Lauren S. Sherman ◽  
Suresh Bhatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Neuronal Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Mscs ◽  
Similar Phenotype

scholarly journals Deciphering Master Gene Regulators and Associated Networks of Human Mesenchymal Stromal Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 557
Author(s):  
Elena Sánchez-Luis ◽  
Andrea Joaquín-García ◽  
Francisco J. Campos-Laborie ◽  
Fermín Sánchez-Guijo ◽  
Javier De las Rivas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Transcription Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Structure ◽  
Regulatory Gene ◽  
Human Mscs ◽  
Protein Activity ◽  
Hematopoietic Stem

Mesenchymal Stromal Cells (MSC) are multipotent cells characterized by self-renewal, multilineage differentiation, and immunomodulatory properties. To obtain a gene regulatory profile of human MSCs, we generated a compendium of more than two hundred cell samples with genome-wide expression data, including a homogeneous set of 93 samples of five related primary cell types: bone marrow mesenchymal stem cells (BM-MSC), hematopoietic stem cells (HSC), lymphocytes (LYM), fibroblasts (FIB), and osteoblasts (OSTB). All these samples were integrated to generate a regulatory gene network using the algorithm ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks; based on mutual information), that finds regulons (groups of target genes regulated by transcription factors) and regulators (i.e., transcription factors, TFs). Furtherly, the algorithm VIPER (Algorithm for Virtual Inference of Protein-activity by Enriched Regulon analysis) was used to inference protein activity and to identify the most significant TF regulators, which control the expression profile of the studied cells. Applying these algorithms, a footprint of candidate master regulators of BM-MSCs was defined, including the genes EPAS1, NFE2L1, SNAI2, STAB2, TEAD1, and TULP3, that presented consistent upregulation and hypomethylation in BM-MSCs. These TFs regulate the activation of the genes in the bone marrow MSC lineage and are involved in development, morphogenesis, cell differentiation, regulation of cell adhesion, and cell structure.

scholarly journals Comparative Analysis of Mesenchymal Stromal Cells Biological Properties

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Angela De Luca ◽  
Rosanna Verardi ◽  
Arabella Neva ◽  
Patrizia Benzoni ◽  
Elisabetta Crescini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Biological Properties ◽  
Human Mscs ◽  
Differentiation Potential ◽  
Tissue Samples

The stromal progenitors of mesodermal cells, mesenchymal stromal cells (MSCs), are a heterogeneous population of plastic adherent fibroblast-like cells with extensive proliferative capacity and differentiation potential. Human MSCs have now been isolated from various tissues including bone marrow, muscle, skin, and adipose tissue, the latter being one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity, and abundance of cells. Bone marrow and subcutaneous or visceral adipose tissue samples were collected, digested with collagenase if needed, and seeded in Iscove's medium containing 5% human platelet lysate. Nonadherent cells were removed after 2-3 days and the medium was replaced twice a week. Confluent adherent cells were detached, expanded, and analyzed for several biological properties such as morphology, immunophenotype, growth rate, senescence, clonogenicity, differentiation capacity, immunosuppression, and secretion of angiogenic factors. The results show significant differences between lines derived from subcutaneous fat compared to those derived from visceral fat, such as the higher proliferation rate of the first and the strong induction of angiogenesis of the latter. We are convinced that the identification of the peculiarities of MSCs isolated from different tissues will lead to their more accurate use in cell therapy.

scholarly journals Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1394
Author(s):  
Luke Watson ◽  
Xi Zhe Chen ◽  
Aideen E. Ryan ◽  
Áine Fleming ◽  
Aoife Carbin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pilot Study ◽  
Fracture Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Flexural Modulus ◽  
Human Mscs ◽  
Mineral Density ◽  
Non Union ◽  
Increased Risk

Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function. Here it was hypothesized that the administration of non-diabetic, human adult bone marrow-derived mesenchymal stromal cells (MSCs) would enhance diabetic fracture healing. Human MSCs were locally introduced to femur fractures in streptozotocin-induced diabetic mice, and the quality of de novo bone was assessed eight weeks later. Biodistribution analysis demonstrated that the cells remained in situ for three days following administration. Bone bridging was evident in all animals. However, a large reparative callus was retained, indicating non-union. µCT analysis elucidated comparable callus dimensions, bone mineral density, bone volume/total volume, and volume of mature bone in all groups that received cells as compared to the saline-treated controls. Four-point bending evaluation of flexural strength, flexural modulus, and total energy to re-fracture did not indicate a statistically significant change as a result of cellular administration. An ex vivo lymphocytic proliferation recall assay indicated that the xenogeneic administration of human cells did not result in an immune response by the murine recipient. Due to this dataset, the administration of non-diabetic bone marrow-derived MSCs did not support fracture healing in this pilot study.

scholarly journals Immune dysfunctionality of replicative senescent mesenchymal stromal cells is corrected by IFNγ priming

2017 ◽  
Vol 1 (11) ◽  
pp. 628-643 ◽  
Author(s):  
Raghavan Chinnadurai ◽  
Devi Rajan ◽  
Spencer Ng ◽  
Kenneth McCullough ◽  
Dalia Arafat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Human Mscs ◽  
Key Points ◽  
Immune Defects

Key Points Replication exhausted human MSCs display attenuated immunosuppressive properties partly because of defective kynurenine production. IFNγ prelicensing can rescue replicative senescence-associated immune defects of human bone marrow–derived MSCs.

Clinical-Scale Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells to Treat Patients After Ischemic Stroke.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3021-3021
Author(s):  
Patrick J Hanley ◽  
Zhuyong Mei ◽  
Bing Yang ◽  
Osman Mir ◽  
Kaushik Parsha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Placebo Control ◽  
Human Mscs ◽  
Average Cell ◽  
Minimum Criteria

Abstract Abstract 3021 Ischemic stroke (IS) is the second leading cause of death worldwide and the leading cause of adult disability. IS patients have few options to limit neurological damage or augment the rehabilitation process. Tissue plasminogen activator, a fibrinolytic agent, is the only FDA approved therapy after IS but it must be administered within 3 hours of onset and is of limited benefit. Based on promising animal studies, another therapeutic option may be the application of mesenchymal stromal cells (MSCs). In one study, autologous MSCs were given to a subset of IS patients. This group showed better survival and neurological improvement, as judged by modified Rankin score and the Barthel index. A significant limitation to the use of autologous MSCs for acute stroke is that cells cannnot be transfused until at least 5 weeks after IS due to the time required for expansion in vitro. We hypothesize that treating patients with MSCs within 48 hours of a stroke may improve outcomes. We plan to expedite the time-to-infusion in two ways. First, banked allogeneic MSCs will be used instead of autologous MSCs to eliminate the production time and convert this to an off-the-shelf therapy. Second, we have compared the use of an automated cell culture device (the Quantum by Terumo BCT), which uses 2.1 m2 of hollow fibers in a bioreactor (equivalent to ∼120 T-175 cm2 flasks), to our current flask-based expansion method. In flasks, human bone marrow (BM) mononuclear cells (BMMC) were separated using the SEPAX device and were seeded at 5,000 BMMC/cm2 in T-175 cm2 flasks and split 1:4 when 70% confluent. After ∼1 month and 3–5 passages, ∼130 T-175 cm2 flasks were harvested and cryopreserved. In the Quantum, ∼25 mL of whole unprocessed BM was added to the bioreactor through a 200 μm filter. After 10 days, the cells were harvested and 2.0–3.5×107 cells were re-seeded in a new bioreactor at ∼1000 MSC/cm2 for a total culture time of ∼17 days. After 3–4 passages in flasks, an average of 2.69×108 MSCs were expanded from three independent BM donors. In two BM donors, MSCs harvested after 2 passages in the Quantum yielded an average of 8.75×108; these cells were frozen and can be used for subsequent expansions. MSCs expanded in both flasks and the Quantum were analyzed by flow cytometry and met the International Society of Cell Therapy (ISCT) minimum criteria for MSC (expression of CD73, CD105, CD90 etc). Expanded MSCs were sterile, were free from chromosomal abnormalities, and differentiated into adipocytes, chondrocytes, and osteoblasts. The production of 5×108 MSCs in flasks required 101 hours of labor compared to 21 hours with the Quantum. We estimated that during the manufacture of MSCs in flasks, there were 600 open (defined as exposing the system to the environment) events compared to 9 in the Quantum. To test the in vivo effects of manufactured MSCs, 24 aged male Long-Evans rats were randomized to receive flask-based human MSCs (P4) or saline vehicle at 7 days after stroke. At 28 days after stroke, animals treated with MSCs showed a significant reduction in neurological deficits compared with saline treated controls. In conclusion, in addition to the advantage of manufacture in a functionally- closed system, large numbers of MSCs expanded in the Quantum were available at a lower passage number with a higher average-cell yield at a slightly higher cost per 5×108 cells. When administered to rats with ischemic stroke, flask-based MSCs improved outcomes compared to placebo control treated animals. Whether MSCs expanded in the Quantum will function with equivalent efficacy is currently being tested and these data will be available for presentation in December. This project is supported by NHLBI-PACT, contract # HHSN268201000007C. Disclosures: Rice: Terumo BCT: Employment.

In Vivo Osteogenic Potential of Mesenchymal Stromal Cells Derived from Patient''s Bone Marrow on Hydroxyapatite Ceramics

2007 ◽  
Vol 330-332 ◽  
pp. 1157-1160 ◽  
Author(s):  
Asako Matsushima ◽  
Noriko Kotobuki ◽  
Hiroko Machida ◽  
Toru Morishita ◽  
Yoshinori Takakura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bone Matrix ◽  
Osteogenic Potential ◽  
Human Mscs ◽  
Hard Tissue ◽  
Culture Dish ◽  
Hydroxyapatite Ceramics

Since 2001, we have started tissue engineered approach for hard tissue repair using mesenchymal stromal cells (MSCs) derived from patient’s bone marrow. MSCs were culture expanded on culture dish, then applied on various ceramics including hydroxyapatite (HA) ceramics. The MSCs on the ceramics were further cultured in osteogenic media to induce osteognenic differentiation. The differentiation resulted in appearance of bone forming osteoblasts as well as bone matrix on the ceramics, thus we could fabricate the tissue engineered bone. We have reported that the tissue engineered bone is effective for treatment of large bone defect, which is difficult to repair only with artificial materials such as HA ceramics. The present study focused on osteogenic capability of cryopreserved human MSCs derived from patients who already were treated by the tissue engineered bone. The MSCs showed high alkaline phosphatase activity together with abundant bone matrix formation when cultured in osteogenic media. The MSCs also showed in vivo new bone formation when implanted at subcutaneous sites of athymic nude rats. Based on the results, we concluded that the tissue engineering approach is a reliable method to be used in hard tissue regeneration.

scholarly journals Human Mesenchymal Stromal Cells from Different Sources Diverge in Their Expression of Cell Surface Proteins and Display Distinct Differentiation Patterns

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Kourosch C. Elahi ◽  
Gerd Klein ◽  
Meltem Avci-Adali ◽  
Karl D. Sievert ◽  
Sheila MacNeil ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
The Elderly ◽  
Free Cell ◽  
Surface Proteins ◽  
Human Mscs ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Clinical Potential

When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor cells is still limited to a few applications, and it mainly applies to mesenchymal stromal cells (MSCs) isolated from bone marrow. But research progressed and different trials explore the clinical potential of human MSCs isolated from bone marrow but also from other tissues including adipose tissue. Recently, MSCs isolated from bone marrow (bmMSCs) were shown to be a blend of distinct cells and MSCs isolated from different tissues show besides some common features also some significant differences. This includes the expression of distinct antigens on subsets of MSCs, which was utilized recently to define and separate functionally different subsets from bulk MSCs. We therefore briefly discuss differences found in subsets of human bmMSCs and in MSCs isolated from some other sources and touch upon how this could be utilized for cell-based therapies.

Mechanisms of action and osteogenic activity of bone marrow mesenchymal stromal cells are donor dependent

2014 ◽  
Author(s):  
Julie Leotot ◽  
Angelique Lebouvier ◽  
Philippe Hernigou ◽  
Helene Rouard ◽  
Nathalie Chevallier
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mechanisms Of Action ◽  
Osteogenic Activity
Sign in / Sign up

Export Citation Format

Share Document