scholarly journals Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues—Origins, Characteristics, Signaling Pathways, and Clinical Trials

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3278
Author(s):  
Magdalena Kulus ◽  
Rafał Sibiak ◽  
Katarzyna Stefańska ◽  
Maciej Zdun ◽  
Maria Wieczorkiewicz ◽  
...  

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

2015 ◽  
Vol 129 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Shoudong Ye ◽  
Dongming Zhang ◽  
Fei Cheng ◽  
Daniel Wilson ◽  
Jeffrey Mackay ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1301
Author(s):  
Jun Liu ◽  
Madeline A. Sauer ◽  
Shaza Hussein ◽  
Junyu Yang ◽  
Daniel G. Tenen ◽  
...  

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene fam-ily. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regard-ing how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as im-portant regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize cur-rent knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.


Development ◽  
2016 ◽  
Vol 143 (3) ◽  
pp. e1.1-e1.1
Author(s):  
Shoudong Ye ◽  
Dongming Zhang ◽  
Fei Cheng ◽  
Daniel Wilson ◽  
Jeffrey Mackay ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4044-4051 ◽  
Author(s):  
Tetsuro-Takahiro Fujimoto ◽  
Satoshi Kohata ◽  
Hidenori Suzuki ◽  
Hiroshi Miyazaki ◽  
Kingo Fujimura

Abstract Megakaryocytes and functional platelets were generated in vitro from murine embryonic stem (ES) cells with the use of a coculture system with stromal cells. Two morphologically distinctive megakaryocytes were observed sequentially. Small megakaryocytes rapidly produced proplatelets on day 8 of the differentiation, and large hyperploid megakaryocytes developed after day 12, suggesting primitive and definitive megakaryopoiesis. Two waves of platelet production were consistently observed in the culture medium. A larger number of platelets was produced in the second wave; 104 ES cells produced up to 108 platelets. By transmission electron microscopy, platelets from the first wave were relatively rounder with a limited number of granules, but platelets from the second wave were discoid shaped with well-developed granules that were indistinguishable from peripheral blood platelets. ES-derived platelets were functional since they bound fibrinogen, formed aggregates, expressed P-selectin upon stimulation, and fully spread on immobilized fibrinogen. These results show the potential utility of ES-derived platelets for clinical applications. Furthermore, production of gene-transferred platelets was achieved by differentiating ES cells that were transfected with genes of interest. Overexpression of the cytoplasmic domain of integrin β3 in the ES-derived platelets prevented the activation of αIIbβ3, demonstrating that this system will facilitate functional platelet studies. (Blood. 2003;102:4044-4051)


2008 ◽  
Vol 283 (51) ◽  
pp. 35929-35940 ◽  
Author(s):  
Shufen Wang ◽  
Yi Shen ◽  
Xiaohua Yuan ◽  
Kai Chen ◽  
Xiangyu Guo ◽  
...  

2011 ◽  
Vol 286 (27) ◽  
pp. 23667-23678 ◽  
Author(s):  
Jung Min Ryu ◽  
Ho Jae Han

Although amino acids can function as signaling molecules in the regulation of many cellular processes, mechanisms surrounding l-threonine involvement in embryonic stem cell (ESC) functions have not been explored. Thus, we investigated the effect of l-threonine on regulation of mouse (m)ESC self-renewal and related signaling pathways. In l-threonine- depleted mESC culture media mRNA of self-renewal marker genes, [3H]thymidine incorporation, expression of c-Myc, Oct4, and cyclins protein was attenuated. In addition, resupplying l-threonine (500 μm) after depletion restores/maintains the mESC proliferation. Disruption of the lipid raft/caveolae microdomain through treatment with methyl-β-cyclodextrin or transfection with caveolin-1 specific small interfering RNA blocked l-threonine-induced proliferation of mESCs. Addition of l-threonine induced phosphorylation of Akt, ERK, p38, JNK/SAPK, and mTOR in a time-dependent manner. This activity was blocked by LY 294002 (PI3K inhibitor), wortmannin (PI3K inhibitor), or an Akt inhibitor. l-threonine-induced activation of mTOR, p70S6K, and 4E-BP1 as well as cyclins and Oct4 were blocked by PD 98059 (ERK inhibitor), SB 203580 (p38 inhibitor) or SP 600125 (JNK inhibitor). Furthermore, l-threonine induced phosphorylation of raptor and rictor binding to mTOR was completely inhibited by 24 h treatment with rapamycin (mTOR inhibitor); however, a 10 min treatment with rapamycin only partially inhibited rictor phosphorylation. l-Threonine induced translocation of rictor from the membrane to the cytosol/nuclear, which blocked by pretreatment with rapamycin. In addition, rapamycin blocked l-threonine-induced increases in mRNA expressions of trophoectoderm and mesoderm marker genes and mESC proliferation. In conclusion, l-threonine stimulated ESC G1/S transition through lipid raft/caveolae-dependent PI3K/Akt, MAPKs, mTOR, p70S6K, and 4E-BP1 signaling pathways.


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