scholarly journals More to Explore; The Mesenchymal Stem Cells (MSCs) Major Tissue Sources, Known Surface Markers, and Its Immunomodulation properties

Mesenchymal stem cells (MSCs) are currently available for a range of applications and have become a good material for regenerative medicine, tissue engineering, and disease therapy. MSCs are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into cell types of mesodermal origin, such as adipocytes, osteocytes, and chondrocytes, and exert potent immunosuppressive potentials. In the present review, we highlight the currently reported variations in the differentiation potential of MSCs from different tissue sources, the minimal criteria to define MSCs from various tissue environments, and provide a detailed description of MSCs surface markers. Furthermore, MSC's immunomodulatory features secrete cytokines and immune receptors which regulate the microenvironment in the host tissue also revisits in detail. We propose that there are likely more sources of MSCs waiting to be discovered. We need to Standardize MSCs characterization by selecting markers for isolation, cellular and molecular mechanisms involved in MSC-mediated immune modulation, and other functionalities of MSCs should be characterized prior to use in clinical applications.

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.


Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ruifeng Liu ◽  
Wenjuan Chang ◽  
Hong Wei ◽  
Kaiming Zhang

Mesenchymal stem cells (MSCs) exhibit high proliferation and self-renewal capabilities and are critical for tissue repair and regeneration during ontogenesis. They also play a role in immunomodulation. MSCs can be isolated from a variety of tissues and have many potential applications in the clinical setting. However, MSCs of different origins may possess different biological characteristics. In this study, we performed a comprehensive comparison of MSCs isolated from bone marrow and skin (BMMSCs and SMSCs, resp.), including analysis of the skin sampling area, separation method, culture conditions, primary and passage culture times, cell surface markers, multipotency, cytokine secretion, gene expression, and fibroblast-like features. The results showed that the MSCs from both sources had similar cell morphologies, surface markers, and differentiation capacities. However, the two cell types exhibited major differences in growth characteristics; the primary culture time of BMMSCs was significantly shorter than that of SMSCs, whereas the growth rate of BMMSCs was lower than that of SMSCs after passaging. Moreover, differences in gene expression and cytokine secretion profiles were observed. For example, secretion of proliferative cytokines was significantly higher for SMSCs than for BMMSCs. Our findings provide insights into the different biological functions of both cell types.


2019 ◽  
Vol 98 (10) ◽  
pp. 1066-1072 ◽  
Author(s):  
V. Yianni ◽  
P.T. Sharpe

Cells have been identified in postnatal tissues that, when isolated from multiple mesenchymal compartments, can be stimulated in vitro to give rise to cells that resemble mature mesenchymal phenotypes, such as odontoblasts, osteoblasts, adipocytes, and myoblasts. This has made these adult cells, collectively called mesenchymal stem cells (MSCs), strong candidates for fields such as tissue engineering and regenerative medicine. Based on evidence from in vivo genetic lineage–tracing studies, pericytes have been identified as a source of MSC precursors in vivo in multiple organs, in response to injury or during homeostasis. Questions of intense debate and interest in the field of tissue engineering and regenerative studies include the following: 1) Are all pericytes, irrespective of tissue of isolation, equal in their differentiation potential? 2) What are the mechanisms that regulate the differentiation of MSCs? To gain a better understanding of the latter, recent work has utilized ChIP-seq (chromatin immunoprecipitation followed by sequencing) to reconstruct histone landscapes. This indicated that for dental pulp pericytes, the odontoblast-specific gene Dspp was found in a transcriptionally permissive state, while in bone marrow pericytes, the osteoblast-specific gene Runx2 was primed for expression. RNA sequencing has also been utilized to further characterize the 2 pericyte populations, and results highlighted that dental pulp pericytes are already precommitted to an odontoblast fate based on enrichment analysis indicating overrepresentation of key odontogenic genes. Furthermore, ChIP-seq analysis of the polycomb repressive complex 1 component RING1B indicated that this complex is likely to be involved in inhibiting inappropriate differentiation, as it localized to a number of loci of key transcription factors that are needed for the induction of adipogenesis, chondrogenesis, or myogenesis. In this review, we highlight recent data elucidating molecular mechanisms that indicate that pericytes can be tissue-specific precommitted MSC precursors in vivo and that this precommitment is a major driving force behind MSC differentiation.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Min Kyoung Shin ◽  
Jung-Suk Sung

Human mesenchymal stem cells derived from adipose tissue (hADMSCs) are a desirable candidate in regenerative medicine. hADMSCs secrete growth factors, cytokines, and chemokines and also express various receptors that are important in cell activation, differentiation, and migration to injured tissue. We showed that the expression level of chemokine receptor CXCR6 was significantly increased by ~2.5-fold in adipogenic-differentiated cells (Ad), but not in osteogenic-differentiated cells (Os) when compared with hADMSCs. However, regulation of CXCR6 expression on hADMSCs by using lentiviral particles did not affect the differentiation potential of hADMSCs. Increased expression of CXCR6 on Ad was mediated by both receptor recycling, which was in turn regulated by secretion of CXCL16, and de novo synthesis. The level of soluble CXCL16 was highly increased in both Ad and Os in particular, which inversely correlates with the expression on a transmembrane-bound form of CXCL16 that is cleaved by disintegrin and metalloproteinase. We concluded that the expression of CXCR6 is regulated by receptor degradation or recycling when it is internalized by interaction with CXCL16 and by de novo synthesis of CXCR6. Overall, our study may provide an insight into the molecular mechanisms of the CXCR6 reciprocally expressed on differentiated cells from hADMSCs.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Cicione ◽  
Emma Muiños-López ◽  
Tamara Hermida-Gómez ◽  
Isaac Fuentes-Boquete ◽  
Silvia Díaz-Prado ◽  
...  

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects thein vitrodifferentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Peter Mark ◽  
Mandy Kleinsorge ◽  
Ralf Gaebel ◽  
Cornelia A. Lux ◽  
Anita Toelk ◽  
...  

Human Mesenchymal Stem Cells (hMSCs) present a promising tool for regenerative medicine. However,ex vivoexpansion is necessary to obtain sufficient cells for clinical therapy. Conventional growth media usually contain the critical component fetal bovine serum. For clinical use, chemically defined media will be required. In this study, the capability of two commercial, chemically defined, serum-free hMSC growth media (MSCGM-CD and PowerStem) for hMSC proliferation was examined and compared to serum-containing medium (MSCGM). Immunophenotyping of hMSCs was performed using flow cytometry, and they were tested for their ability to differentiate into a variety of cell types. Although the morphology of hMSCs cultured in the different media differed, immunophenotyping displayed similar marker patterns (high expression of CD29, CD44, CD73, and CD90 cell surface markers and absence of CD45). Interestingly, the expression of CD105 was significantly lower for hMSCs cultured in MSCGM-CD compared to MSCGM. Both groups maintained mesenchymal multilineage differentiation potential. In conclusion, the serum-free growth medium is suitable for hMSC culture and comparable to its serum-containing counterpart. As the expression of CD105 has been shown to positively influence hMSC cardiac regenerative potential, the impact of CD105 expression onto clinical use after expansion in MSCGM-CD will have to be tested.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mandana Mohyeddin Bonab ◽  
Fatemeh Talebian ◽  
Aida Borzabadi ◽  
Vahideh Nasr ◽  
Azam Abedi Kooshlshahi ◽  
...  

Abstract Background Mesenchymal Stem Cells (MSCs) are multipotent cells with low immuonogenecity, and dynamic tissue repair potential, which explains the overwhelming attention they have attracted in regenerative therapy. One notable challenge in MSCs therapy is the bench to bed timeline of freshly cultured MSCs; it does not exceed 24 h. For use after 24 h, MSC need to be cryopreserved - which can preserve the cells for years - but it is a costly and damaging process. Here we introduce a method to extend the bench to bed lifetime of MSCs up to 4 days without the high cost and cell damaging effects of cryopreservation. Our method is based on preserving the MSCs in human plasma. Methods MSCs of 12 tissue samples - 4 adipose, 4 bone marrow and 4 Wharton’s jelly- were cultured and expanded in standard conditions. Cells harvested from passage 2 or 3 were washed, centrifuged, pelleted, and re-suspended in human plasma. Cell suspensions were refrigerated (5 ± 3 °C) or stored at room temperature (22 ± 3 °C) in a sterile, temperature controlled room. During the next 7 days, two tubes (one from each group) were examined every 24 h to assess MSCs viability and growth potential. On day 3, we assessed MSC cell surface markers and its differentiation potential to adipocyte and osteocyte tissues. Results were analyzed by computing the overall mean and applying the independent-samples t-test to those means. Results The sample means for both cell expansion and cell viability were compared between the two “refrigerator” and “room temperature” groups. Although there was a gradual decrease in cell growth potential between the cells stored for 1 day to those stored for 7 days, we show more than 80% of the cells remain alive for up to 4 days of storage in both groups. The cells reached 80% confluency in under 20 days for all samples stored up to 4 days. No significant differences were observed between the two groups (room temperature and refrigerator stored). The differentiation potential to adipocyte and osteocyte tested on day 3 were positive in all samples. The analysis of cell surface markers tested on day 3 were positive for CD90, CD105, CD73 and negative for CD34, CD45 and HLA-DR. Conclusion We present a method of MSC culture medium using human plasma that can preserve their viability and growth potential for up to 4 days in both room and refrigerator temperatures without losing their stemness characteristics (we recommend use of 5 ± 3 °C). This novel method will allow rapid expansion and therapeutic use of MSCs. Since the cells can be maintained in clinical grade, injection ready state for several days, they can be transported across the globe.


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