What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroboratedin vivoin a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression ofHLA-DRA,HO-1,IGFBP1, 4 and 6,ILR1,IL6RandPTGESand increased expression ofCD200,CD273,CD274,IL1B,IL-8,LIFandTGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1β, IL-8, LIF and TGFβ2.

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Use of In Vivo Gene Expression of Isolated Bone Marrow Mesenchymal Stromal Cells to Study the Pathophysiology of Osteoporosis in Patients With Severe Thalassemia

Journal of Pediatric Hematology/Oncology ◽

10.1097/mph.0b013e318205e24d ◽

2011 ◽

Vol 33 (3) ◽

pp. 179-184 ◽

Cited By ~ 2

Author(s):

Suradej Hongeng ◽

Chokdee Wongborisuth ◽

Sinee Disthabanchong ◽

Samart Pakakasama ◽

Pat Mahachoklertwattana ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells

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Arrhythmogenic Cardiomyopathy Is a Multicellular Disease Affecting Cardiac and Bone Marrow Mesenchymal Stromal Cells

Journal of Clinical Medicine ◽

10.3390/jcm10091871 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1871

Author(s):

Arianna Scalco ◽

Cristina Liboni ◽

Roberta Angioni ◽

Anna Di Bona ◽

Mattia Albiero ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Protein Profile ◽

Cell Types ◽

Fatty Tissue ◽

Arrhythmogenic Cardiomyopathy ◽

Additional Cell

Arrhythmogenic cardiomyopathy (AC) is a familial cardiac disorder at high risk of arrhythmic sudden death in the young and athletes. AC is hallmarked by myocardial replacement with fibro-fatty tissue, favoring life-threatening cardiac arrhythmias and contractile dysfunction. The AC pathogenesis is unclear, and the disease urgently needs mechanism-driven therapies. Current AC research is mainly focused on ‘desmosome-carrying’ cardiomyocytes, but desmosomal proteins are also expressed by non-myocyte cells, which also harbor AC variants, including mesenchymal stromal cells (MSCs). Consistently, cardiac-MSCs contribute to adipose tissue in human AC hearts. We thus approached AC as a multicellular disorder, hypothesizing that it also affects extra-cardiac bone marrow (BM)-MSCs. Our results show changes in the desmosomal protein profile of both cardiac- and BM- MSCs, from desmoglein-2 (Dsg2)-mutant mice, accompanied with profound alterations in cytoskeletal organization, which are directly caused by AC-linked DSG2 downregulation. In addition, AC BM-MSCs display increased proliferation rate, both in vitro and in vivo, and, by using the principle of the competition homing assay, we demonstrated that mutant circulating BM-MSCs have increased propensity to migrate to the AC heart. Taken altogether, our results indicate that cardiac- and BM- MSCs are additional cell types affected in Dsg2-linked AC, warranting the novel classification of AC as a multicellular and multiorgan disease.

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Recruitment of bone marrow-derived mesenchymal stromal cells by umbilical cord-derived mesenchymal stromal cells via G-CSF-mediated mechanism promotes wound healing in vivo

Toxicology Letters ◽

10.1016/j.toxlet.2017.07.833 ◽

2017 ◽

Vol 280 ◽

pp. S298

Author(s):

Sérgio P. Camões ◽

J. Miguel Santos ◽

Alexandre De la Fuente ◽

Miguel Abal ◽

Matilde Castro ◽

...

Keyword(s):

Bone Marrow ◽

Wound Healing ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells

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Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00049.2020 ◽

2020 ◽

Vol 319 (2) ◽

pp. L197-L210 ◽

Cited By ~ 1

Author(s):

Stefanie Noel Sveiven ◽

Tara M. Nordgren

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Phase 1 ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Cell Types ◽

Tissue Type ◽

Published Data

Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950–60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Importantly, these cells are efficient mediators of tissue repair, regeneration, and prove to be targets for therapeutics, demonstrated by clinical trials ( phase 1– 4) for MSC-derived therapies for diseases like graft-versus-host-disease, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. The tissue-resident status of MSC found in the lung is a key feature of their importance in the context of disease and injuries of the respiratory system, since these cells could be instrumental to providing more specific and targeted therapies. Currently, bone marrow-derived MSC have been established in the treatment of disease, including diseases of the lung. However, with lung-resident MSC representing a unique population with a different phenotypic and gene expression pattern than MSC derived from other tissues, their role in remediating lung inflammation and injury could provide enhanced efficacy over bone marrow-derived MSC methods. Through this review, lung-resident MSC will be characterized, using previously published data, by surface markers, gene expression patterns, and compared with bone-marrow MSC to highlight similarities and, importantly, differences in these cell types.

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Umbilical cord tissue derived mesenchymal stromal cells inhibit lysophosphatidylcholine mediated activation of microglia in organotypic cerebellar cultures

Cytotherapy ◽

10.1016/j.jcyt.2017.02.279 ◽

2017 ◽

Vol 19 (5) ◽

pp. S193

Author(s):

A. Saha ◽

L. Xu ◽

R. Franczak ◽

P. Noldner ◽

N. Meadows ◽

...

Keyword(s):

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Umbilical Cord Tissue ◽

Cerebellar Cultures

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Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽

10.3390/cells10020403 ◽

2021 ◽

Vol 10 (2) ◽

pp. 403

Author(s):

Girolamo Di Maio ◽

Nicola Alessio ◽

Ibrahim Halil Demirsoy ◽

Gianfranco Peluso ◽

Silverio Perrotta ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

White Adipocyte ◽

Drug Candidates ◽

Fat Depots ◽

Treatment Of Obesity ◽

White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

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Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo

Stem Cell Research & Therapy ◽

10.1186/s13287-015-0053-x ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 65

Author(s):

Lynn M Pezzanite ◽

Lisa A Fortier ◽

Douglas F Antczak ◽

Jennifer M Cassano ◽

Margaret M Brosnahan ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Allogeneic Bone Marrow ◽

Antibody Responses ◽

Allogeneic Bone

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POSTNATAL EXTRA-EMBRYONIC TISSUES AS A SOURCE OF MULTIPLE CELL TYPES FOR REGENERATIVE MEDICINE APPLICATIONS

Experimental Oncology ◽

10.31768/2312-8852.2017.39(3):186-190 ◽

2017 ◽

Vol 39 (3) ◽

pp. 186-190 ◽

Cited By ~ 1

Author(s):

O S Gubar ◽

A I Rodnichenko ◽

R G Vasylie ◽

A V Zlatska ◽

D O Zubov

Keyword(s):

Regenerative Medicine ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Umbilical Vein ◽

Cell Types ◽

Population Doubling ◽

Embryonic Tissues ◽

Chorionic Membrane ◽

Multiple Cell

Aim: We aimed to isolate and characterize the cell types which could be obtained from postnatal extra-embryonic tissues. Materials and Methods: Fresh tissues (no more than 12 h after delivery) were used for enzymatic or explants methods of cell isolation. Obtained cultures were further maintained at 5% oxygen. At P3 cell phenotype was assessed by fluorescence-activated cell sorting, population doubling time was calculated and the multilineage differentiation assay was performed. Results: We have isolated multiple cell types from postnatal tissues. Namely, placental mesenchymal stromal cells from placenta chorionic disc, chorionic membrane mesenchymal stromal cells (ChM-MSC) from free chorionic membrane, umbilical cord MSC (UC-MSC) from whole umbilical cord, human umbilical vein endothelial cells (HUVEC) from umbilical vein, amniotic epithelial cells (AEC) and amniotic MSC (AMSC) from amniotic membrane. All isolated cell types displayed high proliferation rate together with the typical MSC phenotype: CD73+CD90+CD105+CD146+CD166+CD34-CD45-HLA-DR-. HUVEC constitutively expressed key markers CD31 and CD309. Most MSC and AEC were capable of osteogenic and adipogenic differentiation. Conclusion: We have shown that a wide variety of cell types can be easily isolated from extra-embryonic tissues and expanded ex vivo for regenerative medicine applications. These cells possess typical MSC properties and can be considered an alternative for adult MSC obtained from bone marrow or fat, especially for allogeneic use.

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