scholarly journals Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

2021 ◽  
pp. 112740
Author(s):  
Priscilla Barros Delben ◽  
Helena Debiazi Zomer ◽  
Camila Acordi da Silva ◽  
Rogério Schutzler Gomes ◽  
Fernanda Rosene Melo ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Genetic Integrity ◽  
Long Term Culture

scholarly journals Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

2021 ◽  
Author(s):  
Priscilla B Delben ◽  
Helena D Zomer ◽  
Camila A Silva ◽  
Rogerio S Gomes ◽  
Fernanda R Melo ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Genetic Integrity ◽  
Cell Therapies ◽  
Long Term Culture ◽  
Morphological Alterations ◽  
Fat Depots

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization, but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γH2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.

scholarly journals Senescence-associated metabolomic phenotype in primary and iPSC-derived mesenchymal stromal cells

2019 ◽  
Author(s):  
Eduardo Fernandez-Rebollo ◽  
Julia Franzen ◽  
Jonathan Hollmann ◽  
Alina Ostrowska ◽  
Matteo Oliverio ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Cell Types ◽  
Cellular Aging ◽  
Metabolic Switch ◽  
Differentiation Potential ◽  
Long Term Culture ◽  
Functional Changes

Long-term culture of primary cells is reflected by functional and secretory changes, which ultimately result in replicative senescence. In contrast, induced pluripotent stem cells (iPSCs) do not reveal any signs of cellular aging while in the pluripotency state, whereas little is known how they senesce upon differentiation. Furthermore, it is largely unclear how the metabolome of cells changes during replicative senescence and if such changes are consistent across different cell types. In this study, we have directly compared culture expansion of primary mesenchymal stromal cells (MSCs) and iPSC-derived MSCs (iMSCs) until they reached growth arrest after a mean of 21 and 17 cumulative population doublings, respectively. Both cell types acquired similar changes in morphology, in vitro differentiation potential, up-regulation of senescence-associated beta-galactosidase, and senescence-associated DNA methylation changes. Furthermore, MSCs and iMSCs revealed overlapping gene expression changes during culture expansion, particularly in functional categories related to metabolic processes. We subsequently compared the metabolome of MSCs and iMSCs at early and senescent passages and observed various significant and overlapping senescence-associated changes in both cell types, including down-regulation of nicotinamide ribonucleotide and up-regulation of orotic acid. Replicative senescence of both cell types was consistently reflected by the metabolic switch from oxidative to glycolytic pathways. Taken together, long-term culture of iPSC-derived MSCs evokes very similar molecular and functional changes as observed in primary MSCs. Replicative senescence is associated with a highly reproducible senescence-associated metabolomics phenotype, which may be used to monitor the state of cellular aging.

GENETIC INTEGRITY OF HUMAN ADIPOSE DERIVED MESENCHYMAL STROMAL CELLS FROM FACE AND ABDOMEN IN LONG-TERM CULTURE AND UVB RADIATION.

Cytotherapy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 16-17
Author(s):  
C Acordi-Silva ◽  
P Barros-Delben ◽  
HD Zomer ◽  
RS Gomes ◽  
AG Trentin
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Genetic Integrity ◽  
Uvb Radiation ◽  
Long Term Culture

scholarly journals Isolation and Expansion of Mesenchymal Stem/Stromal Cells, Functional Assays and Long-Term Culture Associated Alterations of Cellular Properties

2021 ◽  
Author(s):  
Chenghai Li
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mhc Class Ii ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Cell Types ◽  
Long Term Culture ◽  
Medicine Research

Mesenchymal stem cell/stromal cells (MSCs) can differentiate into a variety of cell types, including osteocytes, adipocytes and chondrocytes. MSCs are present in the multiple types of adult tissue, such as bone marrow, adipose tissue, and various neonatal birth-associated tissues. Given their self-renewal and differentiation potential, immunomodulatory and paracrine properties, and lacking major histocompatibility complex (MHC) class II molecules, MSCs have attracted much attention for stem cell-based translational medicine research. Due to a very low frequency in different types of tissue, MSCs can be isolated and expanded in vitro to derive sufficient cell numbers prior to the clinical applications. In this chapter, the methodology to obtain primary bone marrow-derived MSCs as well as their in vitro culture expansion will be described. To assess the functional properties, differentiation assays, including osteogenesis, chondrogenesis and adipogenesis, 3-D culture of MSCs and co-culture of MSCs and tumor cells are also provided. Finally, the long-term culture associated alterations of MSCs, such as replicative senescence and spontaneous transformation, will be discussed for better understanding of the use of MSCs at the early stages for safe and effective cell-based therapy.

scholarly journals Clonal chromosomal and genomic instability during human multipotent mesenchymal stromal cells long-term culture

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192445 ◽  
Author(s):  
Victoria Nikitina ◽  
Tatiana Astrelina ◽  
Vladimir Nugis ◽  
Aleksandr Ostashkin ◽  
Tatiana Karaseva ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Long Term Culture

scholarly journals DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells

Aging Cell ◽  
2010 ◽  
Vol 9 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Simone Bork ◽  
Stefan Pfister ◽  
Hendrik Witt ◽  
Patrick Horn ◽  
Bernhard Korn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Methylation Pattern ◽  
Long Term Culture ◽  
Human Mesenchymal Stromal Cells ◽  
Dna Methylation Pattern

scholarly journals Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Emilie P Buddingh ◽  
S Eriaty N Ruslan ◽  
Christianne M A Reijnders ◽  
Karoly Szuhai ◽  
Marieke L Kuijjer ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Long Term Culture ◽  
Show Evidence

scholarly journals Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Ya-fei Qin ◽  
De-jun Kong ◽  
Hong Qin ◽  
Yang-lin Zhu ◽  
Guang-ming Li ◽  
...  
Keyword(s):  
T Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Th17 Cells ◽  
Memory T Cells ◽  
Transplant Recipients ◽  
Pathological Changes ◽  
Allograft Vasculopathy

BackgroundChronic rejection characterized by chronic allograft vasculopathy (CAV) remains a major obstacle to long-term graft survival. Due to multiple complicated mechanisms involved, a novel therapy for CAV remains exploration. Although mesenchymal stromal cells (MSCs) have been ubiquitously applied to various refractory immune-related diseases, rare research makes a thorough inquiry in CAV. Meanwhile, melatonin (MT), a wide spectrum of immunomodulator, plays a non-negligible role in transplantation immunity. Here, we have investigated the synergistic effects of MT in combination with MSCs in attenuation of CAV.MethodsC57BL/6 (B6) mouse recipients receiving BALB/c mouse donor aorta transplantation have been treated with MT and/or adipose-derived MSCs. Graft pathological changes, intragraft immunocyte infiltration, splenic immune cell populations, circulating donor-specific antibodies levels, cytokine profiles were detected on post-operative day 40. The proliferation capacity of CD4+ and CD8+ T cells, populations of Th1, Th17, and Tregs were also assessed in vitro.ResultsGrafts in untreated recipients developed a typical pathological feature of CAV characterized by intimal thickening 40 days after transplantation. Compared to untreated and monotherapy groups, MT in combination with MSCs effectively ameliorated pathological changes of aorta grafts indicated by markedly decreased levels of intimal hyperplasia and the infiltration of CD4+ cells, CD8+ cells, and macrophages, but elevated infiltration of Foxp3+ cells. MT either alone or in combination with MSCs effectively inhibited the proliferation of T cells, decreased populations of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. MT synergized with MSCs displayed much fewer splenic populations of CD4+ and CD8+ T cells, Th1 cells, Th17 cells, CD4+ central memory T cells (Tcm), as well as effector memory T cells (Tem) in aorta transplant recipients. In addition, the percentage of splenic Tregs was substantially increased in the combination therapy group. Furthermore, MT combined with MSCs markedly reduced serum levels of circulating allospecific IgG and IgM, as well as decreased the levels of pro-inflammatory IFN-γ, TNF-α, IL-1β, IL-6, IL-17A, and MCP-1, but increased the level of IL-10 in the recipients.ConclusionsThese data suggest that MT has synergy with MSCs to markedly attenuate CAV and provide a novel therapeutic strategy to improve the long-term allograft acceptance in transplant recipients.

Sign in / Sign up

Export Citation Format

Share Document