scholarly journals Mesenchymal stem cells – a historical overview

2020 ◽  
Vol 8 (2) ◽  
pp. 83-87
Author(s):  
Katarzyna Stefańska ◽  
Rut Bryl ◽  
Lisa Moncrieff ◽  
Nelson Pinto ◽  
Jamil A. Shibli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Therapy ◽  
Osteogenic Potential ◽  
Experimental Medicine ◽  
Cancer Tissue ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Clinical Utilization ◽  
History Of

AbstractMesenchymal stem cells are currently one of the most extensively studied topics in experimental medicine, given their unique properties in terms of immunomodulation, multiple factors secretion and homing to injured tissue sites. Such characteristics were proven to be invaluable in various disease management treatments, for example in cancer, tissue regeneration or immunologic/inflammatory-related disorders. MSCs were first isolated from bone marrow in 1960-1970’s and were characterized as cells with fibroblastoid shape and osteogenic potential, which form clonogenic colonies (CFU-F – colony-forming unit-fibroblast). Nowadays the term ‘mesenchymal stem cells’ is used in regards to all of the cells meeting minimal criteria published in 2006 by the International Society for Cellular Therapy, however the name ‘mesenchymal stromal cells’ has been suggested to be more appropriate. Regardless of the name controversy, these cells exhibit multilineage differentiation potential, self-renewal ability, adhere to plastic and express specific surface antigens. In 2011 the first commercial product based on MSCs was developed and many more are expected to emerge. This review focuses on a historical perspective concerning studies on MSCs, controversies regarding their name and their characteristics and clinical utilization.Running title: The history of mesenchymal stem cells

scholarly journals The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Monika Marędziak ◽  
Krzysztof Marycz ◽  
Krzysztof A. Tomaszewski ◽  
Katarzyna Kornicka ◽  
Brandon Michael Henry
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Population Doubling ◽  
Osteogenic Potential ◽  
Population Doubling Time ◽  
Joint Diseases ◽  
Differentiation Potential ◽  
Age Related

Tissue regeneration using human adipose derived mesenchymal stem cells (hASCs) has significant potential as a novel treatment for many degenerative bone and joint diseases. Previous studies have established that age negatively affects the proliferation status and the osteogenic and chondrogenic differentiation potential of mesenchymal stem cells. The aim of this study was to assess the age-related maintenance of physiological function and differentiation potential of hASCs in vitro. hASCs were isolated from patients of four different age groups: (1) >20 years (n=7), (2) >50 years (n=7), (3) >60 years (n=7), and (4) >70 years (n=7). The hASCs were characterized according to the number of fibroblasts colony forming unit (CFU-F), proliferation rate, population doubling time (PDT), and quantified parameters of adipogenic, chondrogenic, and osteogenic differentiation. Compared to younger cells, aged hASCs had decreased proliferation rates, decreased chondrogenic and osteogenic potential, and increased senescent features. A shift in favor of adipogenic differentiation with increased age was also observed. As many bone and joint diseases increase in prevalence with age, it is important to consider the negative influence of age on hASCs viability, proliferation status, and multilineage differentiation potential when considering the potential therapeutic applications of hASCs.

scholarly journals Human umbilical cord stem cells – the discovery, history and possible application

2020 ◽  
Vol 8 (2) ◽  
pp. 78-82
Author(s):  
Katarzyna Stefańska ◽  
Rut Bryl ◽  
Greg Hutchings ◽  
Jamil A. Shibli ◽  
Marta Dyszkiewicz-Konwińska
Keyword(s):  
Stem Cells ◽  
Umbilical Cord ◽  
Cellular Therapy ◽  
Umbilical Vein ◽  
Embryonic Stem ◽  
Experimental Medicine ◽  
Human Umbilical Cord ◽  
History Of ◽  
Umbilical Cord Stem Cells ◽  
Umbilical Cords

AbstractStem cells are now one of the most extensively studied fields in experimental medicine. Although embryonic stem cells (ESCs) have the capability to differentiate into lineages derived from all three primary germ layers, their use remains ethically controversial. Mesenchymal stromal cells’ (MSCs) utilization is not burdened with such concerns. MSCs were primarily characterized as fibroblastic cells from bone marrow stroma, with the ability to adhere to plastic and form clonogenic colonies (CFU-Fs – colony-forming unit-fibroblasts). Subsequent studies led to their isolation from various other adult or perinatal tissues, including the umbilical cord. Although in most cases MSCs are obtained from umbilical cords’ stroma (Wharton’s jelly), it has been demonstrated that both cord’s lining and endothelial layer of umbilical vein possess the cells that fulfill the minimal criteria for MSCs published in 2006 by the International Society for Cellular Therapy. Since the initial discovery, a number of pre-clinical and clinical studies were conducted with the use of MSCs derived from umbilical cords, targeting diseases such as cancer or autoimmune diseases. Moreover, their secretome may be even more beneficial, providing an opportunity to create cell-free therapies.Running title: The history of human umbilical cord stem cells

scholarly journals ID: 1054 Comparison between fresh and cryopreserved Human Amnion Mesenchymal Stem Cells (HAMCs) in terms of serial passaging, morphology and differentiation potential during long term culture

2017 ◽  
Vol 4 (S) ◽  
pp. 134
Author(s):  
Sandra Lisa Gumpil ◽  
Kamaruzaman Ampon ◽  
Helen Lasimbang ◽  
Simat Siti Fatimah ◽  
S.Vijay Kumar
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Mesenchymal Stem Cells ◽  
Cellular Therapy ◽  
Enzymatic Digestion ◽  
Positive Staining ◽  
Differentiation Potential ◽  
Human Amnion ◽  
Long Term Culture

The therapeutic efficiency of Human Amnion Mesenchymal stem cells (HAMCs) is significantly promising. However, its sustainability in long term sub-cultivation has yet to be identified, especially post-cryopreservation. There are concerns whether stem cells which are cryopreserved will be able to retain its functions and differentiation potential efficiently. The aim of this study is to determine the effects of cryopreservation on the serial passaging, morphology and differentiation potential of HAMCs culture post-cryopreservation compared to fresh HAMCs culture. HAMCs was isolated through serial enzymatic digestion of the amnion membrane of human term placenta after delivery. Fresh HAMCs cultures were sub-cultivated until passage 15 while cryopreserved HAMCs samples was preserved at passage 2 of the cell culture and revived after 3 months of cryopreservation period. Through microscopic observation, the cryopreserved HAMCs started to flatten and become larger in size, losing it fibroblastic feature as early as passage 6. The enlarged and flatten morphological features of the HAMCs indicate that the cells began to lose its proliferative activity at this point. In comparison, the HAMCs normally began to enlarge when reaching passage 15 in non-cryopreserved HAMCs cultures. Fresh HAMCs cultures were able to be sustained up to 15 passages while cryopreserved HAMCs were not able to survive pass 10 passages of cell culture. Furthermore, it was observed that both fresh and cryopreserved HAMCs were able to retain its differentiation potential through osteogenesis and adipogenesis medium induction. This was experimentally visualized through positive staining of the calcium composite and lipid droplet in the induced HAMCs culture using Von Kossa stain solution and Oil Red-O stain solution, respectively. Despite retaining it differentiation potential, cryopreserved HAMCs were only able to survive a few passages after being revived. The result suggests that fresh HAMCs is a more suitable candidate to be used in cellular therapy and various clinical application as it were able to retain all its function in long term culture.

scholarly journals Characterization of Human Mesenchymal Stem Cells from Different Tissues and Their Membrane Encasement for Prospective Transplantation Therapies

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Eva Schmelzer ◽  
Daniel T. McKeel ◽  
Jörg C. Gerlach
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Cell Fusion ◽  
Human Mesenchymal Stem Cells ◽  
Surface Markers ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Donor Cells ◽  
Different Tissues

Human mesenchymal stem cells can be isolated from various organs and are in studies on therapeutic cell transplantation. Positive clinical outcomes of transplantations have been attributed to both the secretion of cytokines and growth factors as well as the fusion of donor cells with that of the host. We compared human mesenchymal stem cells from six different tissues for their transplantation-relevant potential. Furthermore, for prospective allogenic transplantation we developed a semipermeable hollow-fiber membrane enclosure, which would prevent cell fusion, would provide an immune barrier, and would allow for easy removal of donor cells from patients after recovery. We investigated human mesenchymal stem cells from adipose tissue, amniotic tissue, bone marrow, chorionic tissue, liver, and umbilical cord. We compared their multilineage differentiation potential, secretion of growth factors, and the expression of genes and surface markers. We found that although the expression of typical mesenchymal stem cell-associated gene THY1 and surface markers CD90 and CD73 were mostly similar between mesenchymal stem cells from different donor sites, their expression of lineage-specific genes, secretion of growth factors, multilineage differentiation potential, and other surface markers were considerably different. The encasement of mesenchymal stem cells in fibers affected the various mesenchymal stem cells differently depending on their donor site. Conclusively, mesenchymal stem cells isolated from different tissues were not equal, which should be taken into consideration when deciding for optimal sourcing for therapeutic transplantation. The encasement of mesenchymal stem cells into semipermeable membranes could provide a physical immune barrier, preventing cell fusion.

Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

Drug Research ◽  
2018 ◽  
Vol 68 (08) ◽  
pp. 450-456 ◽  
Author(s):  
Leila Mousazadeh ◽  
Effat Alizadeh ◽  
Nosratollah Zarghami ◽  
Shahryar Hashemzadeh ◽  
Sedigheh Aval ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Ex Vivo ◽  
Osteogenic Potential ◽  
Differentiation Potential ◽  
Deacetylase Inhibitor

Abstract Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.

scholarly journals Identification of WNT16 as a Predictable Biomarker for Accelerated Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Hee Kim ◽  
Kyung-Ah Cho ◽  
Hyun-Ji Lee ◽  
Minhwa Park ◽  
Han Su Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Selection Criterion ◽  
Osteogenic Potential ◽  
Differentiation Potential ◽  
Real Time Quantitative Pcr ◽  
Single Cell Cloning

The application of mesenchymal stem cells (MSCs) for treating bone-related diseases shows promising outcomes in preclinical studies. However, cells that are isolated and defined as MSCs comprise a heterogeneous population of progenitors. This heterogeneity can produce variations in the performance of MSCs, especially in applications that require differentiation potential in vivo, such as the treatment of osteoporosis. Here, we aimed to identify genetic markers in tonsil-derived MSCs (T-MSCs) that can predict osteogenic potential. Using a single-cell cloning method, we isolated and established several lines of nondifferentiating (ND) or osteoblast-prone (OP) clones. Next, we performed transcriptome sequencing of three ND and three OP clones that maintained the characteristics of MSCs and determined the top six genes that were upregulated in OP clones. Upregulation of WNT16 and DCLK1 expression was confirmed by real-time quantitative PCR, but only WNT16 expression was correlated with the osteogenic differentiation of T-MSCs from 10 different donors. Collectively, our findings suggest that WNT16 is a putative genetic marker that predicts the osteogenic potential of T-MSCs. Thus, examination of WNT16 expression as a selection criterion prior to the clinical application of MSCs may enhance the therapeutic efficacy of stem cell therapy for bone-related complications, including osteoporosis.

scholarly journals Human amniotic mesenchymal stem cells combined with PPCNg facilitate injured endometrial regeneration

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jiayue Huang ◽  
Wenwen Zhang ◽  
Jie Yu ◽  
Yating Gou ◽  
Nizhou Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fluorescence Imaging ◽  
Surface Markers ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Qrt Pcr ◽  
Amniotic Mesenchymal Stem Cells ◽  
Endometrial Regeneration

Abstract Background Caused by the injury to the endometrial basal layer, intrauterine adhesions (IUA) are characterized by uterine cavity obliteration, leading to impaired fertility. Human amniotic mesenchymal stem cells (hAMSCs) have the potential to promote endometrial regeneration mainly through paracrine ability. PPCNg is a thermoresponsive biomaterial consisted of Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) mixed with gelatin, which has been reported as a scaffold for stem cell transplantation. This study aims to investigate the therapeutic effect of hAMSCs combined with PPCNg transplantation in promoting the regeneration of injured endometrium. Methods hAMSCs were cultured in different concentrates of PPCNg in vitro, and their proliferation, apoptosis and cell cycle were examined by CCK-8 assay and flow cytometry. Immunofluorescence was used to determine the MSCs specific surface markers. The expression of pluripotent genes was analyzed by qRT-PCR. The multiple-lineage differentiation potential was further evaluated by detecting the differentiation-related genes using qRT-PCR and specific staining. The Sprague–Dawley (SD) rat IUA model was established with 95% ethanol. hAMSCs combined with PPCNg were transplanted through intrauterine injection. The retention of DiR-labeled hAMSCs was observed by vivo fluorescence imaging. The endometrium morphology was assessed using hematoxylin and eosin (H&E) and Masson staining. Immunohistochemistry staining was performed to detect biomarkers related to endometrial proliferation, re-epithelialization, angiogenesis and endometrial receptivity. The function of regenerated endometrium was evaluated by pregnancy tests. Results hAMSCs maintained normal cell proliferation, apoptosis and cell cycle in PPCNg. Immunofluorescence and qRT-PCR showed that hAMSCs cultured in PPCNg and hAMSCs cultured alone expressed the same surface markers and pluripotent genes. hAMSCs exhibited normal multilineage differentiation potential in PPCNg. Vivo fluorescence imaging results revealed that the fluorescence intensity of hAMSCs combined with PPCNg intrauterine transplantation was stronger than that of direct hAMSCs intrauterine transplantation. Histological assays showed the increase in the thickness of endometrial and the number of endometrial glands, and the remarkably decrease in the fibrosis area in the PPCNg/hAMSCs group. The expressions of Ki-67, CK7, CK19, VEGF, ER and PR were significantly increased in the PPCNg/hAMSCs group. Moreover, the number of implanted embryos and pregnancy rate were significantly higher in the PPCNg/hAMSCs group than in the hAMSCs group. Conclusions PPCNg is suitable for growth, phenotype maintenance and multilineage differentiation of hAMSCs. hAMSCs combined with PPCNg intrauterine transplantation can facilitate the regeneration of injured endometrium by improving utilization rates of hAMSCs, and eventually restore reproductive capacity.

scholarly journals Deregulated mito-nuclear communication alters chromatin plasticity and differentiation potential of mesenchymal stem cells upon ageing

2020 ◽  
Author(s):  
Andromachi Pouikli ◽  
Swati Parekh ◽  
Monika Maleszewska ◽  
Maarouf Baghdadi ◽  
Ignacio Tripodi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Osteogenic Potential ◽  
Acetyl Coa ◽  
Differentiation Potential ◽  
General Decline ◽  
Age Dependent ◽  
Transcriptional Output

ABSTRACTAgeing is accompanied by a general decline in the function of many cellular pathways, with metabolic alterations, epigenetic modifications, and stem cell exhaustion representing three important hallmarks of the ageing process. However, whether these pathways are causally or functionally related at a molecular level remains poorly understood. Here, we use bone marrow-derived mesenchymal stem cells (MSCs) isolated from young and old mice to address how age-dependent changes in metabolism and epigenetics are linked and how they impact on the ageing transcriptome and differentiation potential. Given that MSCs maintain specific age-associated properties even under prolonged culture conditions, such as the age-dependent decrease in osteogenic differentiation, they are an excellent model to investigate in vitro the connection of ageing hallmarks on a mechanistic level. In this study, we demonstrate that upon ageing, osteogenic potential of MSCs declines as a consequence of deregulated mito-nuclear communication, mediated by decreased levels of the citrate carrier (CiC). Age-dependent down-regulation of CiC results in acetyl-CoA trapping within mitochondria, hypo-acetylation of histones and chromatin compaction. Together, these changes lead to an altered transcriptional output and are responsible for the reduced differentiation capacity into osteoblasts. Strikingly, short-term supplementation of aged cells with acetate, an exogenous source for cytosolic acetyl-CoA production, rescues not only the age-associated reduction of histone acetylation, but also the osteogenesis defect, representing a potential target for in vitro MSC rejuvenation.

scholarly journals Epithelial-Mesenchymal Transition-Derived Cells Exhibit Multilineage Differentiation Potential Similar to Mesenchymal Stem Cells

Stem Cells ◽  
2010 ◽  
Vol 28 (8) ◽  
pp. 1435-1445 ◽  
Author(s):  
Venkata Lokesh Battula ◽  
Kurt William Evans ◽  
Brett George Hollier ◽  
Yuexi Shi ◽  
Frank C. Marini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Multilineage Differentiation ◽  
Differentiation Potential ◽  
Mesenchymal Transition
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