Age of the Donor Reduces the Ability of Human Adipose-Derived Stem Cells to Alleviate Symptoms in the Experimental Autoimmune Encephalomyelitis Mouse Model

Scruggs, Brittni A.; Semon, Julie A.; Zhang, Xiujuan; Zhang, Shijia; Bowles, Annie C.; Pandey, Amitabh C.; Imhof, Kathleen M.P.; Kalueff, Allan V.; Gimble, Jeffrey M.; Bunnell, Bruce A.

doi:10.5966/sctm.2013-0026

Cited by 80 publications

(75 citation statements)

References 40 publications

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“…41 For example, aged MSC cells fail to alleviate autoimmune phenotypes in mouse models, a phenomenon that is likely due to reduced migration ability and reduced expression of anti-inflammatory cytokines. 42,43 Aged MSCs also show reduced ability to repair bone fracture and decreased response to PTH(1-34) treatment. 44 Furthermore, aging makes MSC cells more susceptible to stress-induced senescence.…”

Section: Aging Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues

Liu

Xia

2015

Exp Biol Med (Maywood)

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The aging population and the incidence of aging-related diseases such as osteoporosis are on the rise. Aging at the tissue and organ levels usually involves tissue stem cells. Human and animal model studies indicate that aging affects two aspects of mesenchymal stem cell (MSC): a decrease in the bone marrow MSC pool and biased differentiation into adipocyte at the cost of osteoblast, which underlie the etiology of osteoporosis. Aging of MSC cells is also detrimental to some non-skeletal tissues, in particular the hematopoietic system, where MSCs serve as a niche component. In addition, aging compromises the therapeutic potentials of MSC cells, including cells isolated from aged individuals or cells cultured for many passages. Here we discuss the recent progress on our understanding of MSC aging, with a focus on the effects of MSC aging on bone remodeling and hematopoiesis and the mechanisms of MSC aging.

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Section: Aging Of Mscsmentioning

confidence: 99%

Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues

Liu

Xia

2015

Exp Biol Med (Maywood)

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“…Higher expression of HGF in O2 and similar expression value in some groups expressed that there were individual variation between donors but mostly younger donor seems a little higher than older donor. Those various different expression in RNA levels between young and old ASCs were also reported by Scruggs et al (2013). After co-cultured with human ASCs in IVM system, the expression of all genes in cumulus ( Figure 2) were significantly increased and apoptotic ratio also lower than control.…”

Section: Discussionmentioning

confidence: 67%

“…ASCs exhibit stable growth and proliferation kinetics and can differentiate toward osteogenic, chondrogenic, adipogenic, myogenic, or neurogenic lineages in vitro (Scruggs et al 2013;Shimada et al 2006) which has potential as cell feeder in co-culture system. But biologic aging also occurs in stem cells which was shown with secrete less growth factors and other bioactive molecules (Scruggs et al 2013). Those reports showed the important of donor age that should be considered when select ASCs as cell feeder in co-culture system.…”

Section: Introduc Onmentioning

confidence: 99%

The expression of growth factor signaling genes in co-culture IVM

Setiawan

Kim

et al. 2018

Indones. J. Biotechnol.

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The objec ve of this study was to determine the expression of growth factor signaling genes in human adiposederived stem cells (ASCs), porcine oocytes, and cumulus during in vitro matura on (IVM). The human ASCs (from 2 young and 2 old donors) were used for the co-culture IVM system. The matura on rate was examined based on polar body extrusion. The expression of the growth factor signaling genes from ASCs, oocytes, and cumulus were measured using qPCR. All data were analyzed using ANOVA followed by Tukey's test. The expression of the h-IGF1 signaling genes from human ASCs cells showed similar values in all groups and the h-FGF2 expressions were higher in the young donors than the old ones. The p-FGF2, p-FGFR2, and p-TGFβ1 expressions in the oocytes as well as p-IGFR in the cumulus that were co-cultured from the young donors showed higher values than the old and control groups. The apopto c ra o (p-BAX/p-BCL2) from the oocytes and cumulus in both co-culture groups also showed lower levels than the control (P<0.05). Oocyte matura on rates were significantly increased in all co-cultured groups (Y1 (85.9 ± 2.2%), Y2 (91.2 ± 1.1%), O1 (86.3 ± 1.5%), and O2 (86.5 ± 2.3%)) compared with the control (76.7 ± 1.1%; P<0.05). Although the expression of growth factor signaling genes was varied, young donors' ASCs might support in vitro matura on be er than those from old donors.KEYWORDS co-culture; gene expression; human ASCs; oocytes matura on Introduc onIn vitro maturation (IVM) technique have been essential and important to retrieve high quality mature oocytes for optimum result in the further study, such as embryo production, xenotransplantation and animal model research (Woods and Tilly 2012;Coticchio et al. 2015;Arat et al. 2016). The oocyte is a unique and highly specialized cell responsible for creating, activating and controlling the embryonic genome, as well as supporting basic processes, such as cellular homeostasis, metabolism and cell cycle progression in the early embryo. Oocytes maturation were occurred when the oocytes reached nuclear and cytoplasmic maturation (Coticchio et al. 2015). Nuclear maturation encompasses numerous sequential events, including the breakdown of the germinal vesicle and the resumption of meiosis, the first meiotic division, and the appearance of second metaphase chromosomes. These processes can be evaluated cytologically by the appearance of the first polar body or metaphase II chromosomes (Machtinger et al. 2016). Cytoplasmic maturation occurs alongside of nuclear maturation, involving dramatic changes in oocyte gene expression, protein synthesis, and organelle organization (Woods and Tilly 2012;Machtinger et al. 2016).Cumulus cells have been considered to play an important role in oocyte maturation by keeping the oocyte under meiotic arrest, inducing meiotic resumption and by supporting cytoplasmic maturation. These functions have been attributed to their gap junctions and their specific metabolizing capabilities. Physical contact between oocyte and cumulus cells has been ...

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“…In mouse ASCs, the level of secreted HGF increases with age despite a decrease in VEGF [26]. In human ASCs, basal levels of HGF in ASCs from donors >60 years of age are similar to levels in young ASCs from donors <35 years of age, although inducible expression of HGF by macrophage-CM is impaired in ASCs from older donors [45]. In human amnion MSCs, the expression levels of HGF do not change after serial passages, although the levels of VEGF and FGF-2 decrease in a passage number-dependent manner [46].…”

Section: Discussionmentioning

confidence: 86%

Influence of Donor Age and Passage Number on Angiogenic Activity in Human Adipose-Derived Stem Cell-Conditioned Media

Nakamura¹,

Kazama²,

Nagaoka³

et al. 2015

J Stem Cell Res Ther

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Introduction: Adipose-derived stem/stromal cells (ASCs) are considered a promising cell source for therapeutic angiogenesis because the cells can be prepared following a minimally invasive procedure and because they secrete a variety of angiogenic cytokines. In the present study, the influence of donor age and passage number on angiogenic activity of ASC-conditioned media (ASC-CM) was examined.Methods: Human ASCs (donor age, 5 months to 82 years; n = 10) were cultured, and ASC-CM were collected at passages 2, 4, and 6. The angiogenic activity of ASC-CM was evaluated with the tube formation assay using a system in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were co-cultured. The concentrations of vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF) in each ASC-CM were measured using an enzyme-linked immunosorbent assay. Results:A donor age over 60 years affected the proliferative capacity of ASCs at passage 4 and later. ASC-CM significantly enhanced HUVEC tube formation, and this response was not influenced by donor age. ASC-CM at passage 6 showed a lower tube formation capacity compared to ASC-CM at passage 4, although the capacity was still equivalent to the positive control (medium containing10 ng/mL VEGF-A). A donor age over 26 years affected VEGF-A but not HGF levels in ASC-CM, although we found no direct correlation between VEGF-A/HGF levels and the tube formation capacity. Conclusion:Our results demonstrate a passage number-dependent but a donor age-independent decline in the angiogenic activity of ASC-CM.

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Age of the Donor Reduces the Ability of Human Adipose-Derived Stem Cells to Alleviate Symptoms in the Experimental Autoimmune Encephalomyelitis Mouse Model

Cited by 80 publications

References 40 publications

Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues

Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues

The expression of growth factor signaling genes in co-culture IVM

Influence of Donor Age and Passage Number on Angiogenic Activity in Human Adipose-Derived Stem Cell-Conditioned Media

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