Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner

Abstract Background Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown. Method Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs). Results The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog and Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases. Conclusion Dex preconditioning improved the hMSCs immunomodulatory property and may have reduced the challenge associated with minimal potency and strengthen their therapeutic efficacy. Graphical Abstract Preconditioning of tissue specific hMSCs with dexamethasone biomanufacturers the enhanced potential hMSCs with better stemness and immunomodulatory properties for future therapeutics.

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Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells for regenerative therapies

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0030-1268919 ◽

2011 ◽

Vol 59 (S 01) ◽

Author(s):

M Stubbendorff ◽

T Deuse ◽

K Tang-Quan ◽

H Reichenspurner ◽

RC Robbins ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Immunomodulatory Properties ◽

Regenerative Therapies

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ADIPOGENIC DIFFERENTIATION OF HUMAN FETAL BONE MARROW DERIVED MESENCHYMAL STEM CELLS USING ROSIGLITAZONE

Tsitologiya ◽

10.31116/tsitol.2018.04.05 ◽

2018 ◽

Vol 6o (4) ◽

pp. 273-278 ◽

Cited By ~ 1

Author(s):

A.V. Revittser ◽

◽

Yu. A. Neguliaev ◽

◽

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipogenic Differentiation ◽

Fetal Bone

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Comparative analysis of the immunomodulatory properties of equine adult-derived mesenchymal stem cells

Cell Medicine ◽

10.3727/215517911x647217 ◽

2012 ◽

Author(s):

Danielle D. Carrade ◽

Michael W. Lame ◽

Michael S. Kent ◽

Kaitlin C. Clark ◽

Naomi J. Walker ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Comparative Analysis ◽

Immunomodulatory Properties

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Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666201229124429 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bruna O. S. Câmara ◽

Bruno M. Bertassoli ◽

Natália M. Ocarino ◽

Rogéria Serakides

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Culture Medium ◽

Adipogenic Differentiation ◽

Medium Composition ◽

Cell Therapies ◽

Insulin Producing Cells ◽

Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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Effect of Osteoking on the osteogenic and adipogenic differentiation potential of rat bone marrow mesenchymal stem cells in vitro

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2435-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Congtao Yu ◽

Lifen Dai ◽

Zhaoxia Ma ◽

Hongbin Zhao ◽

Yong Yuan ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipogenic Differentiation ◽

Differentiation Potential ◽

Marrow Mesenchymal Stem Cells ◽

Rat Bone

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The Effects of Andrographolide on the Enhancement of Chondrogenesis and Osteogenesis in Human Suprapatellar Fat Pad Derived Mesenchymal Stem Cells

Molecules ◽

10.3390/molecules26071831 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1831

Author(s):

Thitianan Kulsirirat ◽

Sittisak Honsawek ◽

Mariko Takeda-Morishita ◽

Nuttanan Sinchaipanid ◽

Wanvisa Udomsinprasert ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipogenic Differentiation ◽

Human Mesenchymal Stem Cells ◽

Fat Pad ◽

Alizarin Red ◽

Lineage Differentiation ◽

Expression Of Genes ◽

Dose Dependent ◽

Oil Red O Staining

Andrographolide is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculata, and widely used for its potential medical properties. However, there are no reports on the effects of andrographolide on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of andrographolide on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. The results revealed that andrographolide had no cytotoxic effects when the concentration was less than 12.5 µM. Interestingly, andrographolide had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, andrographolide can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, andrographolide suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. These findings confirm that andrographolide can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine.

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Effects of continuous passage on the immunomodulatory properties of equine bone marrow-derived mesenchymal stem cells in vitro

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2021.110203 ◽

2021 ◽

Vol 234 ◽

pp. 110203

Author(s):

Shannon S. Connard ◽

Renata L. Linardi ◽

Kayla M. Even ◽

Alix K. Berglund ◽

Lauren V. Schnabel ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Immunomodulatory Properties ◽

Equine Bone

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Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

Stem Cells International ◽

10.4061/2011/201371 ◽

2011 ◽

Vol 2011 ◽

pp. 1-18 ◽

Cited By ~ 57

Author(s):

Chad M. Teven ◽

Xing Liu ◽

Ning Hu ◽

Ni Tang ◽

Stephanie H. Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Epigenetic Regulation ◽

Adult Stem Cells ◽

Es Cells ◽

Adipogenic Differentiation ◽

Embryonic Stem ◽

Cell Types ◽

Differentiation Potential ◽

Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

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