Age affects the paracrine activity and differentiation potential of human adipose‑derived stem cells

Park, Jeong Seop; Park, Gabee; Hong, Hoon Pyo

doi:10.3892/mmr.2020.11799

Cited by 27 publications

(24 citation statements)

References 31 publications

(38 reference statements)

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“…Nevertheless, it should be noted that ADSC activity could be affected by age or disease, even though its impact is less than in BMSCs [30][31][32][33]. In practice, ADSCs from the elderly show relatively low differentiation potential, slow proliferation, insufficient paracrine ability, and rapid senescence compared to the young [30,33,34]. These data suggest that the autologous application of ADSCs the elderly requires a confident strategy to improve the cellular activity of ADSCs before transplantation.…”

Section: Introductionmentioning

confidence: 99%

“…Various preclinical studies have induced ADSC differentiation into bone tissue [27][28][29]. Nevertheless, it should be noted that ADSC activity could be affected by age or disease, even though its impact is less than in BMSCs [30][31][32][33]. In practice, ADSCs from the elderly show relatively low differentiation potential, slow proliferation, insufficient paracrine ability, and rapid senescence compared to the young [30,33,34].…”

Section: Introductionmentioning

confidence: 99%

“…For enhanced differentiation, ADSCs should mount an appropriate cellular response to extracellular stimuli to activate differentiation. However, aging/senescence impairs paracrine potential and receptor occupancy of ADSC, creating a deficiency of essential secretory factors [33,43]. Accordingly, the modulation of the secretory condition of ADSCs is surmised to be decisive for its differentiation potential.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, FGF-2 expression is reduced with aging in various tissues [50,51]. TGF-β1 and VEGF have also been reported to enhance bone formation, but their levels are relatively unaffected by aging [33,52,53].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, HGF induces VEGF expression, aiding bone formation through its angiogenic properties [57]. The secretion of HGF is also reduced by cellular senescence, disease, or donor age [33].…”

Section: Introductionmentioning

confidence: 99%

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Priming with a Combination of FGF2 and HGF Restores the Impaired Osteogenic Differentiation of Adipose-Derived Stem Cells

Park

Kim

Hong

2022

Cells

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Classical aging-associated diseases include osteoporosis, diabetes, hypertension, and arthritis. Osteoporosis causes the bone to become brittle, increasing fracture risk. Among the various treatments for fractures, stem cell transplantation is currently in the spotlight. Poor paracrine/differentiation capacity, owing to donor age or clinical history, limits efficacy. Lower levels of fibroblast growth factor 2 (FGF2) and hepatocyte growth factor (HGF) are involved in cell repopulation, angiogenesis, and bone formation in the elderly ADSCs (ADSC-E) than in the young ADSCs (ADSC-Y). Here, we study the effect of FGF2/HGF priming on the osteogenic potential of ADSC-E, determined by calcium deposition in vitro and ectopic bone formation in vivo. Age-induced FGF2/HGF deficiency was confirmed in ADSCs, and their supplementation enhanced the osteogenic differentiation ability of ADSC-E. Priming with FGF2/HGF caused an early shift of expression of osteogenic markers, including Runt-related transcription factor 2 (Runx-2), osterix, and alkaline phosphatase (ALP) during osteogenic differentiation. FGF2/HGF priming also created an environment favorable to osteogenesis by facilitating the secretion of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF). Bone tissue of ADSC-E origin was observed in mice transplanted with FGF/HGF-primed ADSC-E. Collectively, FGF2/HGF priming could enhance the bone-forming capacity in ADSC-E. Therefore, growth factor-mediated cellular priming can enhance ADSC differentiation in bone diseases and thus contributes to the increased efficacy in vivo.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Priming with a Combination of FGF2 and HGF Restores the Impaired Osteogenic Differentiation of Adipose-Derived Stem Cells

Park

Kim

Hong

2022

Cells

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A Multilevel Approach to the Causes of Genetic Instability in Stem Cells

González

2022

Handbook of Stem Cell Therapy

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This chapter addresses the genetic instability in stem cells, a central feature that is an important determinant for the safety and effectiveness of cell-based therapies. First, DNA damage response mechanism and the gene network that regulates the DNA integrity homeostasis are revisited, focusing on relationship between genetic integrity and stemness maintenance. Also, several factors have been included that influence genetic instability in vivo, i.e., ROS generation and inflammation, and in vitro regarding cell isolation, culture conditions, i.e., oxygen levels and the use of feeder layers and different carriers, splitting procedures, passage number, etc. Telomere shortening, replicative senescence aneuploidy, and the senescence-associated secretory phenotype are different processes involved in deterioration of stem cells abilities for homing, reparability, and paracrine modulation. Moreover, less effective DNA repair upon senescence increases the propensity of developing tumors for stem cells that is one the main concerns related to genetic instability in stem cells. Nuclear organization and their determinants linked to chromosome aberrations and aneuploidy in stem cells and those epigenetic changes affecting stability are addressed. Differences between adipose, embryonic, and induced pluripotent stem cells are analyzed regarding to their ontogeny, changes in culture, and variation in proliferative capacity and stemness. The effect of reprogramming methods in genetic instability and variation in mutagenicity according to genes utilized for pluripotency induction, i.e., Yamanaka's factors and others, is discussed. Donor-related factors, i.e., age, smoking, and alcohol consumption, comorbidities, i.e., obesity, insulin resistance, diabetes, are mentioned for wide evaluation of genetic instability. The next years must witness consensus protocols that will contribute to control the effects of factors that alter stem cell genetic stability to increase the security and applicability of cell-based therapy.

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