Mesenchymal Stem Cells Differentiation: Mitochondria Matter in Osteogenesis or Adipogenesis Direction

2020 ◽  
Vol 15 (7) ◽  
pp. 602-606
Author(s):  
Kun Ji ◽  
Ling Ding ◽  
Xi Chen ◽  
Yun Dai ◽  
Fangfang Sun ◽  
...  

Mesenchymal Stem Cells (MSCs) exhibit enormous therapeutic potential because of their indispensable regenerative, reparative, angiogenic, anti-apoptotic, and immunosuppressive properties. MSCs can best differentiate into mesodermal cell lineages, including osteoblasts, adipocytes, muscle cells, endothelial cells and chondrocytes. Specific differentiation of MSCs could be induced through limited conditions. In addition to the relevant differentiation factors, drastic changes also occur in the microenvironment to conduct it in an optimal manner for particular differentiation. Recent evidence suggests that the mitochondria participate in the regulating of direction and process of MSCs differentiation. Therefore, our current review focuses on how mitochondria participate in both osteogenesis and adipogenesis of MSC differentiation. Besides that, in our current review, we try to provide a further understanding of the relationship between the behavior of mitochondria and the direction of MSC differentiation, which could optimize current cellular culturing protocols for further facilitating tissue engineering by adjusting specific conditions of stem cells.

Author(s):  
Kathryn Wingate ◽  
Yan Tan ◽  
Wei Tan

Mesenchymal Stem Cells (MSCs) show great promise for the treatment of cardiovascular diseases by tissue engineering and cell therapy. MSCs are particularly useful for vascular therapies as they are easily obtainable, allogenic, trans-differentiate into specific vascular cells, and assist in regenerating vascular tissue through paracrine signaling. [1] However, the mechanisms which direct MSC trans-differentiation and paracrine signaling are not well defined. [2] Incorrect differentiation of MSC can lead to catastrophic side effects such as the development of a dysfunctional endothelium. [3] To safely utilize these cells for the treatment of vascular diseases it is critical to understand the underlying mechanisms that direct MSC differentiation and paracrine signaling.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Paulina Gil-Kulik ◽  
Małgorzata Świstowska ◽  
Adrianna Kondracka ◽  
Piotr Chomik ◽  
Arkadiusz Krzyżanowski ◽  
...  

The knowledge of factors affecting the viability as well as proliferation and therapeutic potential of perinatal stem cells is of great importance for the decisions concerning their collection, multiplication, and storing. The aim of this work is to evaluate the expression of the BIRC2, BIRC3, and BIRC5 genes at the level of transcription in mesenchymal stem cells derived from the umbilical cord Wharton’s jelly. The study examined the relationship between the expression level of the studied genes and selected biophysical parameters of umbilical blood: pH, pCO2, pO2, and cHCO3. Moreover, the relationship between the pregnant age, the type of delivery (natural delivery or cesarean section), and the level of expression of the BIRC2, BIRC3, and BIRC5 genes was assessed. The research was carried out on mesenchymal stem cells derived from the umbilical cord Wharton’s jelly (WJSC) taken from 55 women immediately after delivery. Expression of the examined genes was assessed with the qPCR method using commercially available reagent kits. On the basis of the conducted research, it was demonstrated that WJSCs collected from younger women giving birth naturally, and in the acidic environment of the umbilical cord blood, are characterized by a higher expression of the BIRC2, BIRC3, and BIRC5 genes. It was shown that the expression of the BIRC2 and BIRC3 genes in Wharton’s jelly mesenchymal stem cells declines with the mother’s age. Our research suggests that stem cells collected from younger women giving birth naturally can be more resistant to apoptosis and show a more stem cell-like character, which can increase their therapeutic potential and clinical utility, but this conclusion needs to be approved in the next studies.


2021 ◽  
Vol 22 (2) ◽  
pp. 684
Author(s):  
Parisa Khayambashi ◽  
Janaki Iyer ◽  
Sangeeth Pillai ◽  
Akshaya Upadhyay ◽  
Yuli Zhang ◽  
...  

Tissue engineering has been an inveterate area in the field of regenerative medicine for several decades. However, there remains limitations to engineer and regenerate tissues. Targeted therapies using cell-encapsulated hydrogels, such as mesenchymal stem cells (MSCs), are capable of reducing inflammation and increasing the regenerative potential in several tissues. In addition, the use of MSC-derived nano-scale secretions (i.e., exosomes) has been promising. Exosomes originate from the multivesicular division of cells and have high therapeutic potential, yet neither self-replicate nor cause auto-immune reactions to the host. To maintain their biological activity and allow a controlled release, these paracrine factors can be encapsulated in biomaterials. Among the different types of biomaterials in which exosome infusion is exploited, hydrogels have proven to be the most user-friendly, economical, and accessible material. In this paper, we highlight the importance of MSCs and MSC-derived exosomes in tissue engineering and the different biomaterial strategies used in fabricating exosome-based biomaterials, to facilitate hard and soft tissue engineering.


Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides

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.


2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.


2014 ◽  
Vol 9 (3) ◽  
pp. 280-289 ◽  
Author(s):  
Lin Zhang ◽  
Ge Feng ◽  
Xing Wei ◽  
Lan Huang ◽  
Aishu Ren ◽  
...  

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 927
Author(s):  
Ki-Taek Lim ◽  
Dinesh-K. Patel ◽  
Sayan-Deb Dutta ◽  
Keya Ganguly

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into different types of mesodermal tissues. In vitro proliferation and differentiation of hMSCs are necessary for bone regeneration in tissue engineering. The present study aimed to design and develop a fluid flow mechanically-assisted cartridge device to enhance the osteogenic differentiation of hMSCs. We used the fluorescence-activated cell-sorting method to analyze the multipotent properties of hMSCs and found that the cultured cells retained their stemness potential. We also evaluated the cell viabilities of the cultured cells via water-soluble tetrazolium salt 1 (WST-1) assay under different rates of flow (0.035, 0.21, and 0.35 mL/min) and static conditions and found that the cell growth rate was approximately 12% higher in the 0.035 mL/min flow condition than the other conditions. Moreover, the cultured cells were healthy and adhered properly to the culture substrate. Enhanced mineralization and alkaline phosphatase activity were also observed under different perfusion conditions compared to the static conditions, indicating that the applied conditions play important roles in the proliferation and differentiation of hMSCs. Furthermore, we determined the expression levels of osteogenesis-related genes, including the runt-related protein 2 (Runx2), collagen type I (Col1), osteopontin (OPN), and osteocalcin (OCN), under various perfusion vis-à-vis static conditions and found that they were significantly affected by the applied conditions. Furthermore, the fluorescence intensities of OCN and OPN osteogenic gene markers were found to be enhanced in the 0.035 mL/min flow condition compared to the control, indicating that it was a suitable condition for osteogenic differentiation. Taken together, the findings of this study reveal that the developed cartridge device promotes the proliferation and differentiation of hMSCs and can potentially be used in the field of tissue engineering.


2021 ◽  
pp. 039139882098680
Author(s):  
Xuefeng Zhang ◽  
Nan Wang ◽  
Yuhua Huang ◽  
Yan Li ◽  
Gang Li ◽  
...  

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.


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